Multifocal mucosa–associated lymphoid tissue lymphoma involving the lungs and the stomach: a rare clinical entity: a case report

© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
Multifocal mucosa–associated lymphoid tissue lymphoma involving the lungs and the stomach: a rare clinical entity: a case report
Carla PM Lam, MB, BS1; CF Wong, FHKCP, FRCP (Edin)2
1 Department of Medicine, Queen Mary Hospital, Pokfulam, Hong Kong
2 Tuberculosis and Chest Medicine Unit, Grantham Hospital, Wong Chuk Hang, Hong Kong
 
Corresponding author: Dr CF Wong (meicarlalam@gmail.com)
 
 Full paper in PDF
 
Case report
A 77-year-old male ex-smoker initially presented to Queen Mary Hospital, Hong Kong in April 2009 with an abnormal lung lesion at the left lower lobe on computed tomography (CT) scan of the abdomen during workup for abdominal aorta aneurysm (Fig 1). The lung lesion persisted despite antibiotic treatment. Flexible bronchoscopy, bronchial brushings and aspirate were unremarkable. It was decided to keep the patient under observation.
 

Figure 1. Computer tomography of the thorax of a 77-year-old man on initial presentation showing left lower lobar consolidation
 
One year later he developed per-rectal bleeding. Colonoscopy was unremarkable but upper endoscopy revealed a 5-cm ulcerative growth in the posterior wall of the proximal gastric body. Histology showed sheets of small abnormal lymphoid cells with pale cytoplasm and cleaved nuclear outline, strongly positive for CD20 and CD79a, and negative for CD3, CD5, CD23, CD10, CD43, and Cyclin-D1. There was lambda light chain restriction. The Ki-67 proliferation index was less than 10%. Lymphoepithelial lesions were identified. Helicobacter pylori was not detected and the patient was treated as a case of isolated primary H pylori–negative gastric mucosa-associated lymphoid tissue (MALT) lymphoma with H pylori eradication followed by rituximab for eight cycles. The response was suboptimal and he was subsequently prescribed three cycles of rituximab, cyclophosphamide, vincristine, and prednisolone.
 
He was admitted to our chest unit in July 2017 for treatment of chest infection. Review of serial chest X-ray and CT scans showed progressive deterioration of the lung lesion that had extended to the whole left lower lobe with consolidative changes, air bronchogram, multiple cystic changes and bronchial dilatation (Fig 2). Serial positron emission tomography–CT scans showed that the lung lesion was metabolically active with partial improvement upon chemotherapy correlating with that of the gastric MALT lymphoma. Repeat fibre-optic bronchoscopy and transbronchial lung biopsy revealed respiratory mucosa with diffuse dense lymphoid proliferation in the stroma. Lymphoepithelial lesions were again observed, positive for CD20 and negative for CD3, CD5, CD10, CD23, and Cyclin-D1. Lambda light chain restriction was demonstrated, compatible with MALT lymphoma.
 

Figure 2. Reassessment computer tomography of the thorax of a 77-year-old man showing bilateral multiple cystic lung lesions, bronchial dilatation, and air-bronchogram
 
Discussion
Mucosa-associated lymphoid tissue lymphoma is a relatively rare disease with an annual incidence estimated at 1/313 000; MALT lymphoma accounts for 6% to 8% of all non-Hodgkin lymphomas. Histologically, MALT lymphoma is characterised by neoplastic cell infiltration around reactive secondary lymphoid follicles in a marginal zone distribution and centrocyte-like cells that are small-to-medium in size with small irregular nuclei. Neoplastic cells frequently have abundant pale cytoplasm and a distinct cell border, resembling small mature lymphocytes. Lymphoepithelial lesions have been frequently described. The immunophenotype of MALT lymphoma is virtually identical to that of non-neoplastic marginal-zone B cells. They are positive for CD20 but negative for IgD, CD5, CD10, Bcl6, and Cyclin-D1. Demonstration of immunoglobulin light chain restriction is also helpful to exclude reactive lymphoid infiltrate. No specific immunohistochemical marker has been identified for MALT lymphoma with different tissues of origin.1
 
The most common site of involvement of MALT lymphoma is the stomach, accounting for half of all cases. Other sites include the small intestine (20%-30%), colon (10%), salivary glands, thyroid, lung, bladder, and skin. Gastric MALT lymphoma is strongly associated with H pylori that has been implicated in its pathogenesis. The majority (92%-98.3%) of gastric MALT lymphomas are positive for H pylori, and H pylori eradication alone achieves complete remission of gastric MALT lymphoma in 80% of cases.
 
Pulmonary MALT lymphoma is a very rare condition, accounting for aproximately 1% of cases. Pulmonary MALT lymphoma is usually an indolent disease and has no association with H pylori but is associated with chronic inflammatory conditions instead. Radiological features of pulmonary MALT lymphoma are diverse and include air bronchogram, bronchial dilation, nodular lesions, lung mass, ground-glass opacities, and cystic lung lesions. Lesions are likely multiple, bilateral without lobar predilection with maximum standardised uptake value varying from 2.8 to 9.4.2
 
Although MALT lymphoma was once thought to be an indolent disease due to its tendency to remain localised for a prolonged period to the tissue of origin, multifocal involvement of MALT lymphoma at presentation has been increasingly reported in recent years.3 4 In a case series of 304 patients with MALT lymphoma in Japan,3 seven (2%) had multifocal involvement, mostly involving the gastrointestinal tract. In another case series in Austria involving 72 patients with non-gastric MALT lymphoma, 23 (32%) had multifocal disease either on presentation or during the study period. Site-specific involvement was reported. The stomach was involved at staging upper endoscopy and histologically confirmed (P<0.0001) in seven of 13 patients with primary lung MALT lymphoma.4
 
There are no specific histological or immunostaining characteristics for MALT lymphoma at different sites. Sequence analysis of immunoglobulin heavy chain gene (IgH) may help demonstrate multifocality of MALT lymphoma. In a study that recruited 170 patients with MALT lymphoma over 8 years, 11 had multifocal involvement and paired tumour biopsy samples were analysed in four.5 Monoclonal rearrangement of the IgH gene was detected in all four tumour pairs of which three had different VDJ sequences, indicating that there was no clonal relationship between the tumour pairs whereas the fourth demonstrated clonal identity. That study implied that MALT lymphomas involving different organ systems more often represent different clones and arise independently instead of disseminating from one system to another.5
 
In our case, we believe that the MALT lymphoma was multifocal in origin and the pulmonary lesion preceded that of the stomach based on the temporal sequence (appearance of lung lesion long before clinical manifestation of gastric MALT lymphoma). Further analysis of the VDJ sequence of the IgH of the tumour samples is needed to demonstrate the clonal relationship between them.
 
Conclusion
Mucosa-associated lymphoid tissue lymphoma was once thought to be an indolent disease localised to one tissue origin, but occurrence of multifocal disease has been increasingly reported. Our case illustrates multifocal MALT lymphoma involving the lungs and the stomach with classic histology, radiological features, and clinical behaviour.
 
Author contributions
All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.
 
Concept or design: All authors.
Acquistition of data: CPM Lam.
Analysis or interpretation of data: CPM Lam.
Drafting of the manuscript: CPM Lam.
Critical revision for important intellectual content: All authors.
 
Conflicts of interest
The authors have disclosed no conflict of interest.
 
Funding/support
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
 
Ethics approval
This study was conducted in accordance with the principles outlined in the Declaration of Helsinki. The patient provided verbal informed consent.
 
References
1. Bacon CM, Du MQ, Dogan A. Mucosa-associated lymphoid tissue (MALT) lymphoma: a practical guide for pathologists. J Clin Pathol 2007;60:361-72. Crossref
2. Zhang WD, Guan YB, Li CX, Huang XB, Zhang FJ. Pulmonary mucosa-associated lymphoid tissue lymphoma: computed tomography and 18F fluorodeoxyglucose-positron emission tomography/computed imaging findings and follow-up. J Comput Assist Tomogr 2011;35:608-13. Crossref
3. Yoshino T, Ichimura K, Mannami T, et al. Multiple organ mucosa-associated lymphoid tissue lymphomas often involve the intestine. Cancer 2001;91:346-53. Crossref
4. de Boer JP, Hiddink RF, Raderer M, et al. Dissemination patterns in non-gastric MALT lymphoma. Haematologica 2008;93:201-6. Crossref
5. Konoplev S, Lin P, Qiu X, Medeiros LJ, Yin CC. Clonal relationship of extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue involving different sites. Am J Clin Pathol 2010;134:112-8. Crossref

Hashimoto’s encephalopathy with partial response to steroid therapy: a case report

© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
Hashimoto’s encephalopathy with partial response to steroid therapy: a case report
Bahar Kaymakamzade, MD1; Senem Ertugrul Mut, MD1; Amber Eker, MD1; Hanife Özkayalar, MD2
1 Department of Neurology, Near East University Faculty of Medicine, Nicosia, Cyprus
2 Department of Pathology, Near East University Faculty of Medicine, Nicosia, Cyprus
 
Corresponding author: Dr Senem Ertugrul Mut (senemertugrul@yahoo.com)
 
 Full paper in PDF
 
Case report
Hashimoto’s encephalopathy (HE), also termed as steroid responsive encephalopathy associated with autoimmune thyroiditis, is a rare and highly variable clinical spectrum. The clinical presentation includes seizures, stroke-like episodes, cognitive decline, neuropsychiatric symptoms, and myoclonus.1 We report a rare and unusual case of HE in which there was a partial response to steroid therapy.
 
A 76-year-old man was admitted to the Department of Neurology of the Near East University Hospital, Cyprus, in October 2016 with the chief complaint of myoclonic jerks and walking difficulty for the past 6 weeks. The patient’s family had observed no significant cognitive or behavioural change. He did not experience any seizure. His medical history included hypertension and diabetes. On neurological examination he was alert and fully oriented. Motor weakness was noted at the left lower extremity with Babinski sign. He had myoclonus in all limbs and bilateral postural tremor, which was predominantly left sided. Magnetic resonance imaging (MRI) scan of the brain revealed widespread T2 hyperintensities mainly in the juxtacortical areas (Fig 1). Blood studies including complete blood count and electrolyte count; liver, renal and thyroid function tests; tumour markers; and paraneoplastic antibody analysis (anti-Hu, -Yo, -Ri, -Ma, -CV2) were all normal. Vasculitis markers including antinuclear antibodies, anti-ds DNA, anticardiolipin immunoglobulin (Ig) M, IgG antibodies, antiphosphatidylserine IgM, IgG antibodies, perinuclear antineutrophil cytoplasmic antibodies, cytoplasmic antineutrophil cytoplasmic antibodies, anti-La and anti-Ro antibodies, and rheumatoid factor were within normal limits. He tested negative for human immunodeficiency virus. His cognitive status worsened during his first week of hospitalisation and he rapidly developed delusions and aggressive behaviour. He was not able to cooperate with the neurocognitive assessment. Electroencephalogram showed 5 to 6 Hz diffuse slow-wave activity without any epileptiform discharge (Fig 2). Cerebrospinal fluid (CSF) analysis showed a very high protein content (1.95 g/L). The CSF/serum glucose ratio was normal. Cerebrospinal fluid investigation and culture was negative, excluding central nervous system infection. Whole-body positron emission tomography was performed to exclude paraneoplastic processes and the result was normal. Consequently, steroid-responsive encephalopathy and associated autoimmune thyroiditis was suspected, and antithyroglobulin antibody (anti-TG-Ab) and antithyroperoxidase antibody (anti-TPO-Ab) levels were studied. Serum level of both was increased (431 IU/mL and 40 IU/mL respectively). He was not taking any medication (eg, lithium, amiodarone, etc) that could account for the positivity of thyroid antibodies. Thyroid ultrasonography did not show any pathological findings. Intravenous pulse steroid treatment (IVPS, methylprednisolone 1 g/day) was started. Myoclonus resolved on the fourth day of treatment. Because the cognitive status of the patient was not adequately changed, IVPS was extended to 10 days. A partial response was obtained in cognition and Mini-Mental State Examination score was 11/30 after IVPS. Another electroencephalogram showed mild improvement. Consequently, oral methylprednisolone was continued at a dosage of 1 mg/kg/day. Afterwards, intravenous Ig treatment was given at a dose of 0.4 g/kg for 5 days. No additional improvement was seen. Lumbar puncture and thyroid autoantibody testing were repeated. The anti-TPO-Ab and anti-TG-Ab levels were normalised, and CSF was acellular at that time and protein content decreased (1.45 g/L). Azathioprine 100 mg/day was gradually added to his treatment. The patient was discharged from the hospital with oral steroid and azathioprine treatment. His neurological status was stable. He died 3 months later due to a lung infection.
 

Figure 1. (a, b) Magnetic resonance images of the brain revealing widespread T2 hyperintensities. (c, d) Magnetic resonance image of the brain revealing widespread T2 hyperintensities mainly in the juxtacortical areas
 

Figure 2. Electroencephalogram showing 5-to-6-Hz diffuse slow wave activity without any epileptiform discharge
 
Discussion
The clinical findings, CSF analysis, and MRI of our patient were compatible with HE. The challenging conditions we faced were the lack of prominent cognitive or psychiatric change at the beginning and normal thyroid functions. The differential diagnosis included vasculitis, paraneoplastic limbic encephalitis, and Creutzfeldt-Jakob disease (CJD). The MRI was very helpful for differential diagnosis. The pattern of isolated cortical hyperintensity with concomitant combined cortical and deep grey matter (basal ganglia) hyperintensity on fluid attenuation inversion recovery along with restricted diffusion can differentiate CJD from other rapidly progressive dementias with a high sensitivity and specificity.2 Because the consecutive diffusion-weighted images of the patient were not compatible with CJD, 14-3-3 assay in the CSF was not studied. In addition, it is not specific for CJD and its positivity is also reported in HE.3 The laboratory and imaging findings were not compatible with limbic encephalitis. We assessed his objective clinical recovery (dramatic disappearance of myoclonus and partial cognitive-behavioural improvement) following pulse steroid therapy. Response to treatment may also exclude the diagnosis of CJD.
 
The pathophysiology of HE is not well understood. Autoimmune cerebral vasculitis and antibody-mediated neuronal reaction are the most accepted mechanisms. Most patients are euthyroid at the time of diagnosis.4 Antithyroperoxidase antibody is known as a positive predictor of responsiveness to steroid therapy and higher titres are associated with a more favourable outcome.5 Most cases in the literature treated with steroids make a complete recovery.5 Since it is a rare condition, the optimum treatment for steroid-resistant cases is unknown. Response to intravenous Ig or plasmapheresis treatments in steroid non-responsive cases has also been reported.5 Despite the normalisation of anti-TPO-Ab and anti-TG-Ab levels and somewhat improved inflammatory findings of CSF after treatment, we observed a complete response in myoclonus and only a partial improvement in cognition in our patient. This supports the hypothesis that thyroid autoantibodies are not the only pathogenic mechanism in HE. Other causes, the role of the thyroid gland, and other antibodies should be clarified by future studies.
 
Author contributions
Concept or design: B Kaymakamzade, S Ertugrul Mut.
Acquisition of data: H Özkayalar, A Eker, S Ertugrul Mut.
Analysis or interpretation of data: B Kaymakamzade.
Drafting of the manuscript: All authors.
Critical revision for important intellectual content: S Ertugrul Mut, B Kaymakamzade.
 
All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.
 
Acknowledgements
We thank Dr Mustafa Canatan and Dr Fehim Türktan for their contribution to the editing of the manuscript.
 
Conflicts of interest
All authors have disclosed no conflicts of interest.
 
Funding/support
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
 
Ethics approval
This study was conducted in accordance with the principles outlined in the Declaration of Helsinki. The patient provided written informed consent.
 
References
1. Mocellin R, Walterfang M, Velakoulis D. Hashimoto’s encephalopathy: epidemiology, pathogenesis and management. CNS Drugs 2007;21:799-811. Crossref
2. Vitali P, Maccagnano E, Caverzasi E, et al. Diffusion-weighted MRI hyperintensity patterns differentiate CJD from other rapid dementias. Neurology 2011;76:1711-9. Crossref
3. Hernández Echebarría LE, Saiz A, et al. Detection of 14-3-3 protein in the CSF of a patient with Hashimoto’s encephalopathy. Neurology 2000;54:1539-40. Crossref
4. Oide T, Tokuda T, Yazaki M, et al. Anti-neuronal autoantibody in Hashimoto’s encephalopathy: neuropathological, immunohistochemical, and biochemical analysis of two patients. J Neurol Sci 2004;217:7-12. Crossref
5. Litmeier S, Prüss H, Witsch E, Witsch J. Initial serum thyroid peroxidase antibodies and long-term outcomes in SREAT. Acta Neurol Scand 2016;134:452-7. Crossref

Malignant otitis externa complicated by multiple cervical-petrous internal carotid artery pseudoaneurysms: a case report

© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
Malignant otitis externa complicated by multiple cervical-petrous internal carotid artery pseudoaneurysms: a case report
James SK Lau, BSc, MB, BS1,2; Jane CY Wong, MB, BS1; Rebecca YT Ng, FCSHK, FHKAM (Surgery)1; Vincent KY Pang, FRCS, FHKAM (Surgery)1; CK Wong, FRCS, FHKAM (Surgery)1
1 Department of Neurosurgery, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong
2 Accident and Emergency Department, Ruttonjee Hospital, Wan Chai, Hong Kong
 
Corresponding author: Dr Jane CY Wong (janewongcy@gmail.com)
 
 Full paper in PDF
 
Case report
Pseudoaneurysms that arise from malignant otitis externa (MOE) are a rare and potentially fatal condition. This is the first reported case of cervical-petrous internal carotid artery (ICA) pseudoaneurysm due to secondary MOE.
 
A 59-year-old man with poorly controlled diabetes mellitus and end-stage renal failure presented with a 1-week history of right ear hearing loss and tinnitus. Tympanic examination was normal and he was treated with intratympanic steroids. Three weeks later he was diagnosed with chronic suppurative otitis media and completed a course of oral ciprofloxacin and ototopic ofloxacin. Despite treatment, his condition deteriorated and he developed otitis externa that was complicated by a grade IV facial nerve palsy after 6 weeks. A pus swab from the ear grew Pseudomonas aeruginosa and biopsy of an aural polyp was compatible with infection. Computed tomography of the temporal bone excluded the presence of osteomyelitis. Over the following 3 months of out-patient consultations, he complained of intermittent otorrhea and was prescribed multiple courses of ciprofloxacin, the longest course lasting 3 weeks.
 
The patient developed fifth and twelfth cranial nerve palsies in addition to facial nerve palsy that persisted for 16 weeks. Computed tomography of the brain revealed lytic changes along the skull base (Fig a and b) and he was diagnosed with grade II MOE. Six weeks of meropenem was commenced but he developed epistaxis and blood-stained otorrhea after 2 weeks. Computed tomography angiogram revealed multiple pseudoaneurysms at the right ICA situated between the subpetrous and proximal cavernous segments (Fig c). His blood pressure was stable throughout with no drop in haemoglobin. Balloon occlusion test (BOT) demonstrated sufficient crosss-hunting to the right anterior circulation via the anterior communicating artery as well as from the right external carotid artery even under hypotensive challenge. The patient remained neurologically stable throughout the test that lasted 40 minutes. Trapping of the right ICA was then performed with coil embolisation of the cervical segment and the horizontal part of the cavernous segment separately (Fig d and e), in order to minimise deposition of any foreign body at the infected region.
 

Figure. (a) Plain computed tomography brain (axial, bone window) showing extensive bony erosion over right temporomandibular joint, sphenoid, petrous apex, and clivus. (b) Brain window of Figure a. (c) Three-dimensional reconstruction of DSA showing multiple pseudoaneurysms at subpetrous and subcavernous segments of the right ICA. (d) Lateral view of the right ICA DSA showing multiple pseudoaneurysms. The subpetrous one (arrow) measuring 4.67 mm × 3.76 mm is believed to be the source of the haemorrhage. A few more were at the subcavernous segment. (e) Control injection of right ICA after trapping showing no forward flow to distal ICA but reflux to right external carotid artery. The infected ICA segment was trapped by two Ruby Coils (Penumbra, Alameda [CA], US) and an Interlock-18 Fibered IDC Occlusion System (Boston Scientific Corporation, Malborough [MA], US) proximally, and three Target Detachable Coils (Stryker, Kalamazoo [MI], US) distally (arrows)
 
Postoperatively, he was stable and was discharged home with an 8-week course of ciprofloxacin and amoxillin clavulanate. Gallium scan was repeated at 3 and 8 weeks postoperatively and revealed further interval decrease in uptake over the right skull with mild residual gallium activity. His otalgia and fifth and twelfth cranial nerve palsy subsided subsequently. Three months after embolisation, he continues to suffer residual grade III 7th nerve palsy and otorrhea.
 
Discussion
Cervical-petrous internal carotid artery pseudoaneurysms can arise from different aetiologies including congenital, trauma, malignancy, radiation therapy, and infection. Cases of ruptured ICA pseudoaneurysm due to otogenic infection are rare with only four cases reported1 2 3 4; these cases were MOE complicated by pseudoaneurysm on only one ICA segment. This is the first reported case of pseudoaneurysm occurring on multiple segments of the ICA with rupture due to MOE, and demonstrates the features that predict development of complex vascular complications of unresolved otogenic infection, the timing of appropriate imaging modalities, and appropriate algorithm and duration of treatments to prevent or rescue a fatal carotid blowout.
 
Malignant otitis externa is becoming an increasingly common condition as a consequence of the prevalence of diabetes and other immunocompromised states. It is an aggressive infection that involves the external ear canal, either primarily originating from the external auditory canal or secondary to chronic suppurative otitis media. Pseudomonas aeruginosa is the most common causative organism.1 Conventionally, MOE is classified according to the structural involvement (Table).5 In stage II MOE, complications can arise as it invades the temporal bone and surrounding nerve and vascular structures causing multiple cranial nerve palsies and carotid pseudoaneurysms. Ruptured mycotic pseudoaneurysm has an alarming mortality rate of 54% due to shock, aspiration and ultimately cardiopulmonary arrest.4 Furthermore, cavernous sinus thrombosis and cerebral venous sinus thrombosis can occur when the internal jugular vein is affected.
 
 

Table. Stages, clinical features, and management of malignant otitis externa
 
In our patient, the time to diagnosis of MOE was 12 weeks compared with an average of 13 weeks.1 Because the possible mechanisms of the palsies include contiguous infectious spread or direct compression by the pseudoaneurysm, it is paramount that we recognise the warning signs of pseudoaneurysm and instigate appropriate investigations and treatment (Table).
 
Treatment of malignant otitis externa and its complications
A prolonged course of culture-directed antibiotics remains the mainstay treatment for osteomyelitis, especially when surgical debridement at the skull base is not feasible. Because Pseudomonas aeruginosa is the most common bacterial organism in MOE, an antipseudomonal antibiotic such as ceftazidime is preferred. With regard to duration, 4 to 6 weeks is optimal with the rationale that bone revascularisation takes 3 to 4 weeks. Gallium-67 citrate scintigraphy and indium scintigraphy scans are sensitive to active infection and can be used to monitor treatment progress, guide duration of antibiotic administration, and prevent recurrence.
 
Other than antibiotics and local debridement and drainage of abscesses, adjuvant hyperbaric oxygen therapy has been reported to improve the clinical course of MOE. Despite the absence of randomised controlled trials, adjuvant hyperbaric oxygen therapy has been shown since the 1980s to be effective in numerous patients. It should be strongly considered in stage II MOE5 to minimise intracranial involvement that brings high mortality. Hyperbaric oxygen therapy is postulated to enhance phagocytic action via free radicals, minimise tissue hypoxia that otherwise leads to further infection and augment antibiotic activity.
 
An endovascular approach is frequently adopted in the treatment of ICA pseudoaneurysm since expertise and accessibility in open surgery are limited.6 Depending on the anatomy of the aneurysm, collateral flow sufficiency and the segment involved, either a reparative or destructive approach is used.6 In a life-threatening scenario, we prefer a more aggressive approach of occluding the parent artery/trapping as it protects both the aneurysm and the frequently diseased ICA segment. A BOT can identify those who cannot tolerate permanent carotid occlusion that has a complication rate of 1.6% for neurological deficits.7 Alternatively, a failure rate of 4.7% and permanent stroke can occur after passing BOT.7 For patients who fail BOT, a reparative approach such as stenting or stent-assisted coiling may be considered but there is a risk of further infection due to foreign body deposition around the infected segment. In this case, we avoided such infection by not implanting coils in the diseased ICA segment. Coils were instead deployed at segments of the ICA both proximal (cervical) and distal (cavernous) to the diseased segment as illustrated in Figure e. Definitively, performing a high-flow bypass prior to surgical ligation of the parent artery can avoid the issues mentioned.
 
The patient in this case had multiple risk factors including longstanding uncontrolled diabetes mellitus and end-stage renal failure. In retrospect, the use of intratympanic steroids along with intermittent antibiotics could have further worsened his clinical course. With progression of symptoms despite antibiotics, we should have had a high clinical suspicion of MOE and treated appropriately before complications developed. In the presence of multiple cranial nerve palsies or even facial nerve palsy alone, timely vascular imaging is crucial to exclude the presence of pseudoaneurysms.
 
In conclusion, this case highlights the rare but important complication of MOE and the warning symptoms associated with pseudoaneurysms. Early involvement of ear, nose, and throat specialists and neurosurgeons can expedite the time to diagnosis and allow for prompt investigations and intervention.
 
Author contributions
All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.
 
Concept or design: All authors.
Acquisition of data: JSK Lau, JCY Wong, RYT Ng.
Analysis or interpretation of data: All authors.
Drafting of the manuscript: JSK Lau, JCY Wong, RYT Ng.
Critical revision for important intellectual content: All authors.
 
Conflicts of interest
All authors have disclosed no conflicts of interest.
 
Funding/support
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
 
Ethics approval
The patient was treated in accordance with the Declaration of Helsinki. The patient provided informed consent for all procedures.
 
References
1. Baker A, Rizk H, Carroll W, Lambert P. Cervical internal carotid artery pseudoaneurysm complicating malignant otitis externa: first case report. Laryngoscope 2015;125:733-5. Crossref
2. Oyama H, Hattori K, Tanahashi S, Kito A, Maki H, Tanahashi K. Ruptured pseudoaneurysm of the petrous internal carotid artery caused by chronic otitis media. Neurol Med Chir (Tokyo) 2010;50:578-80. Crossref
3. Telmesani LM. Ruptured petrous carotid pseudoaneurysm complicating malignant otitis externa. J Otolaryngol 2004;33:278-80.
4. Yagci AB, Ardiç FN, Oran I, Bir F, Karabulut N. Ruptured petrous carotid pseudoaneurysm due to tuberculous otitis: endovascular treatment. Interv Neuroradiol 2006;12:53-6. Crossref
5. Davis JC, Gates GA, Lerner C, Davis MG Jr, Mader JT, Dinesman A. Adjuvant hyperbaric oxygen in malignant external otitis. Arch Otolaryngol Head Neck Surg 1992;118:89-93. Crossref
6. Powitzky R, Vasan N, Krempl G, Medina J. Carotid blowout in patients with head and neck cancer. Ann Otol Rhinol Laryngol 2010;119:476-84. Crossref
7. Mathis JM, Barr JD, Jungreis CA, et al. Temporary balloon test occlusion of the internal carotid artery: experience in 500 cases. AJNR Am J Neuroradiol 1995:16:749-54.

Rosai-Dorfman disease presenting as a solitary soft-tissue mass in the thigh: a case report

© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
Rosai-Dorfman disease presenting as a solitary soft-tissue mass in the thigh: a case report
Alice KY Au, FHKCR, FHKAM (Radiology)1; HM Cheng, FHKCR, FHKAM (Radiology)1; KY Cho, FHKCR, FHKAM (Radiology)1; CW Tam, FHKCR, FHKAM (Radiology)1; Jennifer LS Khoo, FHKCR, FHKAM (Radiology)1; Joshua HY Ng, MB, BS2; Vincent TW Hau, MB, ChB, FHKAM (Orthopaedic Surgery)3
1 Department of Radiology, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong
2 Department of Clinical Pathology, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong
3 Department of Orthopaedics and Traumatology, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong
 
Corresponding author: Dr Alice KY Au (augar520@gmail.com)
 
 Full paper in PDF
 
Case report
A 46-year-old man presented to the Department of Orthopaedics and Traumatology, Pamela Youde Nethersole Eastern Hospital in February 2004 with a 3-month history of self-detected left thigh mass. It was of spontaneous onset with no history of trauma, associated pain, weakness, or numbness. The patient had full range of movement and no lymphadenopathy was noted. Magnetic resonance imaging (MRI) [Fig 1] revealed a large area of infiltrative soft-tissue thickening at the medial aspect of the left distal thigh and involved the subcutaneous layer. The lesion measured 8.4 × 3.4 × 11.2 cm (anteroposterior × transverse × longitudinal) and was characterised by T1-weighted (T1W) hypointense to isointense and T2-weighted (T2W) fat-suppressed hyperintense signals with internal heterogeneity. Internal foci of hypointensity in the T2W fat-suppressed images were noted. An internal reticular pattern of septal thickening was also found. There was enhancement after gadolinium contrast administration. The margin of the lesion was well delineated from the underlying vastus medialis and sartorius muscles with no features of muscular invasion or destruction. The knee joint was unremarkable and bone marrow signal was normal. The neurovascular bundle was also intact. Overall features were non-specific for either inflammatory or neoplastic pathology.
 

Figure 1. (a) Axial T1-weighted magnetic resonance (MR) image showing a large area of infiltrative soft tissue thickening involving the subcutaneous layer at the medial aspect of the thigh with hypo- to iso-intense signals (arrow). (b) Axial T2-weighted fat-suppressed MR image showing hyperintense signals with internal heterogeneity and foci of hypointensities. Internal reticular pattern of septal thickening was present (arrow). (c, d) Axial and coronal T1-weighted fat-suppressed post-contrast MR images showing gadolinium enhancement of the lesion (arrow). The margin of the lesion was well delineated from the underlying vastus medialis and sartorius muscles without features of muscular invasion or destruction (arrow)
 
Microscopic examination of an incisional biopsy over the left vastus medialis with a wedge of skin and subcutaneous tissue revealed infiltrate in the subcutis and to a lesser extent the deep dermis. The infiltrate consisted of lymphocytes and a low number of plasma cells. Immunohistochemical stains showed mainly T-cells and some B-cells. Occasional areas with aggregates of paler histiocytic cells were present and suggested granuloma formation. Stains for acid-fast bacilli and fungus were negative. The paler histiocytic cells were S100-positive and showed lymphophagocytosis (Fig 2). Molecular study by polymerase chain reaction showed no clonal T-cell proliferation. The overall features were suggestive of Rosai-Dorfman disease (RDD).
 

Figure 2. (a) Pale areas of histiocytes with emperipolesis and adjacent areas rich in lymphocytes and plasma cells are evident (haematoxylin and eosin, × 400). (b) Histiocytes are S100-positive on immunostaining. Emperipolesis can also be demonstrated (immunostain for S100, × 600)
 
Radical excision of the lesion was performed subsequently and included the epimysium of the gracilis, sartorius and aponeurosis of the vastus medialis. The excision margin in the radial excision of the lesion was 2 cm. Microscopic examination revealed that the mass in the subcutis was composed of nodules or aggregates of lymphohistiocytic cells separated by areas of fibrosis. The cellular aggregates were composed of dark areas with plasma cells and lymphocytes and pale areas with clusters of histiocytes. The histiocytes showed round vesicular nuclei, distinct nucleoli, and abundant foamy cytoplasm with presence of emperipolesis (phagocytosis of plasma cells and lymphocytes). The histiocytes showed positive immunostaining for S100. Special stains for acid-fast bacilli and fungus were again negative. The overall features were consistent with RDD. The resection margins were unremarkable. The patient recovered well postoperatively.
 
Eight years after the operation, the patient detected a nodular swelling over the inferior margin of the surgical site. Serial MRI showed a static nodular T1W hypointense, and T2W isointense to mildly hyperintense soft-tissue lesion with contrast enhancement, measuring approximately 8 mm in diameter (Fig 3). Features could represent postoperative change or tumour recurrence. The patient was otherwise asymptomatic and he opted for follow-up scans to monitor the lesion instead of surgical excision.
 

Figure 3. (a) Axial T1-weighted (T1W) magnetic resonance (MR) image showing an 8-mm nodular hypointense lesion at the inferior margin of the operative site. (b) Axial T2-weighted fat-suppressed MR image showing an isointense to mildly hyperintense lesion (arrow). (c, d) Axial and coronal T1-weighted fat-suppressed post-contrast MR images showing nodular enhancement of the lesion (arrow). Features could represent postoperative change or tumour recurrence (arrow)
 
Discussion
Rosai-Dorfman disease is also known as sinus histiocytosis with massive lymphadenopathy and was first described by Rosai and Dorfman in 1969.1 It is a rare non-malignant histiocytic proliferative disorder. Although the disease may develop at any age, it is more common in young adults with a mean age of onset of 20 years and a slight male predominance (1.4:1).2 3
 
The aetiology of RDD is unknown, although previous studies have attempted to relate RDD to infectious agents including Epstein-Barr virus, human herpesvirus 6, herpes simplex virus, Brucella, Klebsiella rhinoscleromatis, and Nocardia.4 The disease involves a wide distribution and can affect a multitude of organ systems, including nodal involvement and extranodal involvement. The majority of patients present with painless massive cervical lymphadenopathy. Most patients have a complete and spontaneous remission, but some may experience recurrent or persistent albeit stable lymphadenopathy. In rare cases, the disease may follow an aggressive course and be fatal.
 
Pure cutaneous RDD is a distinct clinical entity that has an older age of onset (median 43.5 years) and a male-to-female ratio of 1:2.3 In contrast to systemic RDD that is commonly seen in blacks and rarely reported in Asians, most patients with purely cutaneous RDD are Asians or whites. The lesion remains localised to the skin even after long-term follow-up.5
 
Histologically, RDD is characterised by sheets of large pale histiocytes with large, round, vesicular nuclei. Phagocytosis of lymphoid cells or neutrophils by histiocytes may be found (“emperipolesis”). Immunohistochemical stains are useful when diagnosing RDD and the most consistent and reliable phenotype for RDD is S100 positive and CD1a negative.
 
Relative to the wide disease spectrum, there are variable radiographic features. Although no specific imaging characteristics allow differentiation of lymphadenopathy in RDD from the myriad other disease processes, massive painless bilateral cervical lymph node enlargement, particularly when it occurs in children and adolescents, should prompt consideration of RDD as a differential diagnosis. Nodal involvement may be evidenced as lymphadenopathy. In computed tomography scan of the sinuses and brain, polypoid masses, mucosal thickening, soft-tissue lesion of the paranasal sinuses or nasal cavity with or without associated osseous erosion can be seen. Features of brain involvement include a hyperattenuating meningeal-based mass showing contrast enhancement or parenchymal oedema surrounding the lesion. In MRI of the sinuses and brain, sinus lesions may also demonstrate hypointensity on T2W images. Meningeal-based mass lesions may demonstrate T1W isointensity to grey matter, T2W hyperintensity to grey matter and homogeneous contrast enhancement.6 Gallium scanning may show increased uptake and increased metabolism with fluorodeoxyglucose positron emission tomography. The differential diagnosis is broad and includes infectious (granulomatous) disease, Wegener’s granulomatosis, other histiocytosis, Hodgkin’s and non-Hodgkin’s lymphoma, and fibroinflammatory lesions. In general, RDD does not show bone or soft-tissue destruction as in cases of Wegener’s granulomatosis and T-cell lymphoma.
 
Rosai-Dorfman disease usually follows a benign and self-limiting course with treatment largely targeted at controlling local manifestations. Surgical options may be warranted for symptomatic control.
 
Author contributions
All authors contributed to the concept or design, acquisition of data, analysis or interpretation of data, drafting of the manuscript, and critical revision for important intellectual content. All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.
 
Conflicts of interest
All authors have disclosed no conflicts of interest.
 
Funding/support
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
 
Ethics approval
This study was conducted in accordance with the Declaration of Helsinki. The patient provided written informed consent.
 
References
1. Rosai J, Dorfman RF. Sinus histiocytosis with massive lymphadenopathy. A newly recognized benign clinical pathologic entity. Arch Pathol 1969;87:63-70.
2. Annessi G, Giannetti A. Purely cutaneous Rosai-Dorfman disease. Br J Dermatol 1996;134:749-53. Crossref
3. Brenn T, Calonje E, Granter SR, et al. Cutaneous Rosai-Dorfman disease is a distinct clinical entity. Am J Dermatopathol 2002;24:385-91. Crossref
4. Lu CI, Kuo TT, Wong WR, Hong HS. Clinical and histopathologic spectrum of cutaneous Rosai-Dorfman disease in Taiwan. J Am Acad Dermatol 2004;51:931-9. Crossref
5. Farooq U, Chacon A, Vincek V, Elgart GW. Purely cutaneous Rosai-Dorfman disease with immunohistochemistry. Indian J Dermatol 2013;58:447-50. Crossref
6. Symss NP, Cugati G, Vasudevan MC, Ramamurthi R, Pande A. Intracranial Rosai Dorfman disease: report of three cases and literature review. Asian J Neurosurg 2010;5:19-30.

Cardiovascular event in chronic myeloid leukaemia treated with tyrosine kinase inhibitor: a case report

© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
Cardiovascular event in chronic myeloid leukaemia treated with tyrosine kinase inhibitor: a case report
YL Boo, MD, MRCP(UK); Christopher CK Liam, MRCP(UK); SY Lim, MD, MRCP(UK); ML Look, MRCP(UK)
Department of Internal Medicine, Hospital Sultanah Nora Ismail, Batu Pahat, Johor, Malaysia
 
Corresponding author: Dr YL Boo (coolrontin@gmail.com)
 
 Full paper in PDF
 
Case report
Chronic myeloid leukaemia (CML) is a myeloproliferative neoplasm arising from a pluripotent haematopoietic stem cell. It is associated with an oncogenic fusion gene BCR-ABL, encoding a protein with tyrosine kinase activity.1 The emergence of tyrosine kinase inhibitors (TKIs) such as imatinib, nilotinib, dasatinib, and ponatinib has revolutionised the treatment and improved overall survival of patients with CML. Pericardial and pleural effusion, pulmonary oedema, left ventricular failure, arrhythmia, and coronary heart disease have rarely been reported in clinical trials with nilotinib.2 We report a case of acute coronary syndrome in a young woman treated with nilotinib.
 
A 33-year-old woman presented to Hospital Sultanah Nora Ismail, Johor, Malaysia in February 2017 with first-episode sudden-onset, left-sided chest pain that lasted more than 30 minutes and was associated with nausea, vomiting, palpitations, and profuse sweating. She had been diagnosed with CML 2 years previously and had initially received imatinib with low Sokal score. Her BCR-ABL1 fusion transcript was more than 0.1% after 1 year of treatment, and thus, her treatment was changed to nilotinib 400 mg twice daily, as a second-line TKI. Tyrosine kinase domain mutation analysis was not performed due to lack of resources. She was compliant with medication and showed a good response with her BCR-ABL1 transcript dropping to less than 0.1% after 3 months of therapy. She had no other significant medical or family history. On arrival, she was haemodynamically stable and physical examination was normal. Her initial blood investigations showed normal haemoglobin level (13.6 g/dL), white cell count (8.3 × 109/L), platelet count (240 × 109/L), kidney, and liver function. Her initial electrocardiogram showed T wave inversion over V2 to V6 with a Q wave in lead III. Subsequent electrocardiograms showed evolving ischaemic changes with ST depression over V2 to V6. Her initial creatine kinase was normal (50 U/L) with negative troponin I, but rose to 950 U/L within 24 hours. Her total cholesterol was 4.2 mmol/L, low-density lipoprotein 1.6 mmol/L, and high-density lipoprotein 0.6 mmol/L. Echocardiography showed normal ejection fraction (55%) with a dilated left atrium and left ventricle. She was diagnosed with non–ST elevation myocardial infarction and started on anticoagulation and dual antiplatelet therapy. Urgent angiography showed 95% distal right coronary artery stenosis with successful angioplasty and stenting (Fig). She was discharged from the hospital well and planned for re-challenge of TKI during follow-up.
 

Figure. Angiograms showing (a) 95% distal right coronary artery stenosis (arrow) and (b) after successful angioplasty and stenting
 
Discussion
Nilotinib, a second-generation TKI, has been shown in the ENESTnd study to induce more rapid and profound molecular responses than imatinib in patients with CML in the chronic phase (CML-CP).2 The proxy measurements of molecular response, MR1.0, MR2.0, MR3.0 and MR4.5 are achieved better, and earlier on, during first-line treatment with nilotinib.2 These measurements predict better overall survival in CML-CP,2 yet no direct proven long-term overall survival benefit has been demonstrable for nilotinib vs imatinib.
 
Cardiovascular adverse events with nilotinib have raised concerns about long-term sequelae of drugs administered for decades with 5% to 13% of patients experiencing cardiovascular events with nilotinib.3 In addition, metabolic effects such as hyperglycaemia, hyperlipidaemia, and increased body mass index have significant implications for cardiovascular outcome in patients treated with nilotinib.2 4 Preliminary studies suggest nilotinib has detrimental effects on endothelial cell function in vitro and may accelerate atherosclerosis in addition to the metabolic effects.5 Therefore, cardiovascular risk assessment needs to be integrated and regular monitoring is important especially in patients at high risk of cardiac disease. Our patient presented with acute coronary syndrome after 1 year of treatment with nilotinib. She was previously taking imatinib, but current evidence suggests a lower incidence of cardiovascular events in patients taking imatinib, even compared with those not taking TKIs (Table).3 Early cardiac intervention and optimisation of risk factors may improve overall morbidity and mortality.
 

Table. Potential cardiovascular events in association with different tyrosine kinase inhibitors3
 
In summary, cardiac events have been reported in CML patients treated with nilotinib. Therefore, it is important to recognise these possible complications. Early treatment can then be instituted to improve overall outcome.
 
Author contributions
All authors contributed to the concept, acquisition of data, analysis of data, drafting of the manuscript, and critical revision of important intellectual content. All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.
 
Acknowledgements
The authors would like to thank the Director General of Health Malaysia for permission to publish this article.
 
Conflicts of interest
All authors have disclosed no conflicts of interest.
 
Funding/support
This paper received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
 
Patient consent
The patient provided written consent for publication.
 
References
1. Vardiman JW, Melo JV, Baccarani M, Thiele J. Chronic myelogenous leukaemia, BCR-ABL1 positive. In: Swerdlow SH, Campo E, Harris NL, et al, editors. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. Lyon: IARC; 2008: 32-7.
2. Saglio G, Kim DW, Issaragrisil S, et al. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med 2010;362:2251-9. Crossref
3. Moslehi JJ, Deininger M. Tyrosine kinase inhibitor-associated cardiovascular toxicity in chronic myeloid leukemia. J Clin Oncol 2015;33:4210-8. Crossref
4. Rea D, Mirault T, Cluzeau T, et al. Early onset hypercholesterolemia induced by the 2nd-generation tyrosine kinase inhibitor nilotinib in patients with chronic phase-chronic myeloid leukemia. Haematologica 2014;99:1197-203. Crossref
5. Emir H, Albrecht-Schgoer K, Huber K, et al. Nilotinib exerts direct pro-atherogenic and anti-angiogenic effects on vascular endothelial cells: a potential explanation for drug-induced vasculopathy in CML. Blood 2013;122:257.

Ciliated muconodular papillary tumour of the lung mimicking mucinous adenocarcinoma: a case report and literature review

© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
Ciliated muconodular papillary tumour of the lung mimicking mucinous adenocarcinoma: a case report and literature review
Florence MF Cheung, MB, BS, FHKAM (Pathology)1; J Guan, MD, PhD1; QG Luo, MD2; Alan DL Sihoe, MBBChir, FHKAM (Surgery)2; XP Shen, MD3
1 Department of Pathology, University of Hong Kong—Shenzhen Hospital, Shenzhen, Guangdong, China
2 Department of Thoracic Surgery, University of Hong Kong—Shenzhen Hospital, Shenzhen, Guangdong, China
3 Department of Radiology, University of Hong Kong—Shenzhen Hospital, Shenzhen, Guangdong, China
 
Corresponding author: Dr Florence MF Cheung (fmfcheung@gmail.com)
 
 Full paper in PDF
 
Case report
Solitary lung nodules of <3 cm in diameter within the lung parenchyma and with no other abnormalities are often picked up incidentally during routine radiographic imaging. The incidence of cancer for such nodules has been estimated to be 10% to 70%. Management strategy depends on the clinical probability of cancer; nodule size, features, and growth rate ascertained by radiology; and the surgical risk to the patient. We report a case of such a nodule revealed by radiology and suspicious for malignancy. Subsequent excision and pathological examination revealed unexpected findings.
 
The index patient was a 61-year-old Chinese man from Northern China with history of laryngeal cancer treated successfully by local surgery and radiotherapy 6 years prior to present admission. Routine chest computed tomography (CT) scan revealed a peripheral lung nodule 9 mm in diameter in the right lower lobe. Follow-up CT scan 1 year later revealed minimal increase in size to 10 mm and the patient was referred to the Department of Thoracic Surgery, University of Hong Kong–Shenzhen Hospital in November 2015 for further treatment. The patient was a former chronic smoker for more than 10 years (10 cigarettes/day) but had stopped smoking upon diagnosis of laryngeal cancer.
 
Physical examination of the patient was unremarkable. High-resolution CT scan confirmed the presence of a peripheral lung nodule in his right lower lobe lateral-basal segment that was suspicious for malignancy. It measured 12 mm in diameter and had a spiculated border with a central cavity (Fig a). Another high-density 2-mm nodule was present in the right upper lobe subpleural region associated with apical fibrosis. There was pleural thickening and mildly increased peripheral lung markings in bilateral lower lobes. The peribronchiolar and hilar lymph nodes were not enlarged. After further examination and assessment of the surgical risk, video-assisted thoracoscopy was decided, with patient consent.
 

Figure. Radiological and pathological findings of the right lower lobe of the lung. (a) High-resolution computed tomography shows right lower lobe lung nodule (red arrow) with spiculated border and central cavity. (b) Lung nodule surrounded by a ring of intra-alveolar mucin (black arrows). Scattered tumour necrosis is seen (red arrows). Inset: Frozen section highlights intra-alveolar growth pattern and central cystic space (haematoxylin & eosin [H&E], ×10). (c) Papillary structures consist of multi-layered mucin-secreting columnar cells (black arrows) and basal cells (red arrow) on fibrous cores (H&E, ×40). (d) Basal cells have mildly atypical nuclei with prominent nucleoli and rare mitosis (white arrow). Inset: ciliated cells (black arrow) (H&E, ×400). (e) Origin of the tumour from a dilated respiratory bronchiole can be demonstrated (outline is black-arrowed) [H&E, ×20]. (f) Section from adjacent lung shows peribronchiolar mucociliated metaplasia (inset: H&E, ×400) of a terminal bronchiole extending into alveolar wall (H&E, ×100)
 
During video-assisted thoracoscopy, wedge excision of the nodule was done. Intra-operative frozen section consultation revealed a 10-mm papillary glandular tumour 8 mm away from the pleura. There was profuse mucin production and intra-alveolar extension suspicious for mucinous adenocarcinoma. Right lower lobectomy was subsequently performed, and the patient had an uneventful recovery. Microscopic examination of formalin-fixed paraffin-embedded sections from the nodule showed an arborising papillary tumour (Fig b) surrounded by intra-alveolar mucin. There was extension along the alveolar lining at its periphery (Fig b, inset) simulating ‘lepidic spread’ of adenocarcinoma. The papillary structures (Fig c and d) consisted of fibrous cores covered by single to multiple layers of mucin-secreting and ciliated (Fig d, inset) columnar cells and basal cells. There was focal tumour necrosis, rare mitoses, and mild nuclear atypia. Mucin and inflammatory cells filled the central cystic space. Origin from a dilated terminal bronchiole could be traced (Fig e). A batch of immunohistochemical studies showed CK7+/CK20- tumour cells mostly negative for thyroid transcription factor-1 except at the periphery, suggestive of residual alveolar lining cells. Monoclonal carcinoembryonic antigen highlighted the mucinous cells and p63 stained the basal cells. Proliferative index by Ki67 was low (5%). The overall picture was consistent with ciliated muconodular papillary tumour (CMNPT) of the lung. Examination of the lobectomy specimen showed focal peribronchiolar fibrosis compatible with the effect of smoking.1 These foci often contained peribronchiolar metaplasia featuring ciliated and mucinous columnar cells (Fig f) occasionally forming small papillae (Fig f, inset). The 2-mm lesion in the right upper lobe was a fibrotic nodule. The patient was well 1 year after surgery.
 
Discussion
The term CMNPT of the lung was first used by Ishikawa in 2002 to describe a 1.5-cm peripheral lung nodule consisting of ciliated columnar cells, mucous cells and basal cells with papillary architecture. It was considered benign in view of indolent behaviour and bland-looking cells. Further reports by Ishikawa2 and others3 4 5 6 7 of similar tumours under various names (eg, solitary peripheral ciliated glandular papillomas, peripheral pulmonary papillary/glandular neoplasms with ciliated cells) supported this group of tumours as a specific entity that has not been included in the 2015 World Health Organization Classification of Lung Tumours.8 We searched the literature and reviewed 12 reports of 33 such tumours (online supplementary Appendix). Controversy exists whether CMNPT should be considered a benign tumour, a well-differentiated adenocarcinoma (in view of frequent intra-alveolar extension), or a spectrum of entities with possible progression. The consistent small size, slow growth rate, and lack of recurrence or metastasis after surgery support the benign nature of this tumour. Differentiation from mucinous adenocarcinoma is difficult for pathologists, especially during intra-operative frozen section, owing to the profuse mucin production and lepidic growth pattern. High-power examination revealing tripartite cell differentiation and lack of significant atypia in a clinically slow-growing lung nodule should raise suspicion of CMNPT. Wedge excision with clear margin is the treatment of choice. Our findings concur with a previous report3 of tumour origin from the terminal bronchiole. The finding of co-existing peribronchiolar metaplasia with similar cell components as CMNPT in the rest of the lung is unique. This suggests progression of disease from smoking-induced metaplasia to neoplasia during the pathogenesis. Although chronic smoking was noted in most male patients with CMNPT (14 out of 16 with smoking history specified in the online supplementary Appendix), co-existing peribronchiolar metaplasia was only briefly mentioned in one report,4 probably owing to limited sampling in wedge excision for most tumours. Molecular analysis for BRAF or EGFR mutations was not done in our case, because there was no therapeutic indication. Studies of CMNPT by Chuang et al5 and Lau et al6 yielded no KRAS or EGFR mutation. In contrast, Kamata et al7 reported mutations involving EGFR, BRAF, PTEN11, CTNNB1, IDH1, and TP53 in Asian patients and Liu et al4 reported mutations involving BRAF and AKT1 in one non-Asian patient. Because CMNPT is commonly reported in patients from East Asia, more reports are expected when awareness of this entity is raised among pathologists in this region. The pathogenesis, molecular characteristics, and natural behaviour of CMNPT can be better defined when more data are available.
 
Author contributions
All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.
 
Concept or design: FMF Cheung.
Acquisition of data: All authors.
Analysis or interpretation of data: All authors.
Drafting of the manuscript: FMF Cheung.
Critical revision for important intellectual content: All authors.
 
Acknowledgement
The authors would like to thank Dr Siu-wah Pang for contributing to the diagnosis of this tumour.
 
Conflicts of interest
All authors have disclosed no conflicts of interest.
 
Funding/support
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
 
Ethics approval
This study was approved by the Ethics Committee of the University of Hong Kong–Shenzhen Hospital as original work with no infringement of personal privacy. The requirement for patient consent was waived by the Ethics Committee.
 
References
1. Katzenstein AL, Mukhopadhyay S, Zanardi C, Dexter E. Clinically occult interstitial fibrosis in smokers: classification and significance of a surprisingly common finding in lobectomy specimens. Hum Pathol 2010;41:316-25. Crossref
2. Ishikawa M, Sumitomo S, Imamura N, et al. Ciliated muconodular papillary tumor of the lung: report of five cases. J Surg Case Rep 2016;2016.pii:rjw144. Crossref
3. Aida S, Ohara I, Shimazaki H, et al. Solitary peripheral ciliated glandular papillomas of the lung: a report of 3 cases. Am J Surg Pathol 2008;32:1489-94. Crossref
4. Liu L, Aesif SW, Kipp BR, et al. Ciliated muconodular papillary tumors of the lung can occur in Western patients and show mutations in BRAF and AKT1. Am J Surg Pathol 2016;40:1631-6. Crossref
5. Chuang HW, Liao JB, Chang HC, Wang JS, Lin SL, Hsieh PP. Ciliated muconodular papillary tumor of the lung: a newly defined peripheral pulmonary tumor with conspicuous mucin pool mimicking colloid adenocarcinoma: a case report and review of literature. Pathol Int 2014;64:352-7. Crossref
6. Lau KW, Aubry MC, Tan GS, Lim CH, Takano AM. Ciliated muconodular papillary tumor: a solitary peripheral lung nodule in a teenage girl. Hum Pathol 2016;49:22-6. Crossref
7. Kamata T, Sunami K, Yoshida A, et al. Frequent BRAF or EGFR mutations in ciliated muconodular papillary tumors of the lung. J Thorac Oncol 2016;11:261-5. Crossref
8. Travis WD, Brambilla E, Burke AP, et al. WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart. Lyon, France: International Agency for Research on Cancer; 2015.

Management of thigh lipofibromatosis in a newborn: a case report

© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
Management of thigh lipofibromatosis in a newborn: a case report
YL Lam, MB, ChB, FHKAM (Orthopaedic Surgery)1; WY Ho, MB, BS, FHKAM (Orthopaedic Surgery)1; Raymond Yau, MB, BS, FHKAM (Orthopaedic Surgery)1; Victor WK Lee, MB, BS2; Tony WH Shek, MB, BS, FHKAM (Pathology)2
1 Department of Orthopaedics and Traumatology, Queen Mary Hospital, Pokfulam, Hong Kong
2 Department of Pathology, Queen Mary Hospital, Pokfulam, Hong Kong
 
Corresponding author: Dr YL Lam (albertlam2000@yahoo.com)
 
 Full paper in PDF
 
Case report
A 3.6 kg (gravida 2 para 2 full-term normal vaginal delivery) baby boy presented to Queen Mary Hospital, Hong Kong in September 2015 with a painless swelling on the left thigh on day 2 after birth. The antenatal check-up had been normal. Physical examination revealed a 2- × 2-cm intramuscular swelling over the lateral aspect of the left thigh. There was mild tenderness but no increase in local temperature, skin change, or thrill. Limb movements were normal and symmetrical. Distal pulse and tissue circulation were also normal. Further systemic examination revealed no syndromal features, other swelling, or other significant findings on other systems.
 
Blood tests revealed slightly deranged white cell count and haemoglobin, creatine kinase, lactate dehydrogenase, and C-reactive protein levels. Renal and liver function tests and calcium and phosphate levels were normal. Radiographs did not show any abnormality. Ultrasonographic study on day 2 after birth revealed a swollen and oedematous distal part of the left vastus lateralis muscle. The muscular architecture was preserved. There was no definite mass and the vascular signal was also normal. A repeat ultrasonographic study in week 2 after birth showed an ill-defined intramuscular echogenic lesion at the distal left vastus lateralis muscle. A magnetic resonance imaging scan at age 2 months showed an infiltrative lesion of 3 × 4 × 4.3 cm in the vastus lateralis muscle with extension to the short head of the biceps muscle. It was heterogeneously hyperintense to the muscle on both T1- and T2-weighted images.
 
An image-guided wide-bore needle biopsy revealed a benign-looking lesion composed of fascicles of spindle cells admixed with lobules of mature fat. The differential diagnoses included lipofibromatosis, fibrous hamartoma of infancy, or less likely, calcifying aponeurotic fibroma, and lipoblastoma or lipoblastomatosis.
 
During the course of the investigation, there was deterioration of knee range in extension. At age 5 months, the flexion contracture was 25 degrees. Clinically, there was size progression. In addition, the parents were concerned about the subjective increase in tumour size. After discussion of the treatment options with the parents, a marginal excision was performed at age 5 months.
 
Microscopic examination of the surgical specimen showed thick fascicles of bland-looking spindle cells traversing a large number of mature adipocytic lobules, concentrated around the septal region (Figs 1 and 2). Infiltration around the skeletal muscle was noted. There was no organoid nest of mesenchymal cells to suggest fibrous hamartoma of infancy, nor any calcification foci to suggest calcifying aponeurotic fibroma. Mitosis was inconspicuous. Necrosis was absent. Immunohistochemical staining of the spindle cells showed CD34+, S100+, and actin patchy+, whereas beta-catenin, epithelial membrane antigen, desmin, and c-kit were negative. A diagnosis of lipofibromatosis was made.
 

Figure 1. Gross specimen (serially sectioned, periphery inked green) showing admixture of whitish area, tan skeletal muscle, and yellowish fat
 

Figure 2. (a) Thick fascicles of spindle cells traversing mature fat lobules, with infiltration of skeletal muscle (right half); (b) bland-looking cytology of the spindle cells in fascicles on higher-power magnification
 
The patient was given postoperative physiotherapy as maintenance for his knee range of motion. The latest follow-up was at 5 months postoperatively (age 10 months). He was able to pull himself to a standing position. He could walk with support for more than 10 steps. Thickened scarring could be felt under the old incision wound. His latest knee range was 0 to 130 degrees (the same as the right side).
 
Discussion
The reported occurrence of neonatal tumours is one in 12 500 to 27 500 live births although there is little information on the real incidence. It has not been well studied because of its rarity.1 Soft tissue tumours account for 25% of all neoplasms in infancy, of which approximately 15% are malignant.2
 
It is quite impossible to clinically differentiate between a benign and a malignant tumour in a child. Further investigation by means of ultrasonography or magnetic resonance imaging may provide a definitive diagnosis in certain conditions such as haemangioma but may be impossible without histological studies.1
 
More confusing, the behaviour of the tumour in this specific patient group may not be the same as in their adult counterparts. The natural history of some disease entities has not been documented. Even a benign lesion may invade locally, causing symptoms such as developmental deformity and even death.1
 
Watchful neglect may be a treatment option for some lesions with a potential of spontaneous regression such as haemangioma.2 In the other conditions, surgical resection may be an option for management of a progressing disease.
 
There are four possible diagnoses based on the first wide-bore needle biopsy finding. Calcifying aponeurotic fibroma3 is tumour characterised by foci of calcification, palisaded round cells and radiating arms of fibroblasts. This lesion has a high tendency of local recurrence (50%). The natural history is tumour growth reduction with age. Conservative resection or palliative resection should be considered.
 
Lipoblastoma or the diffuse subtype lipoblastomatosis3 is a benign tumour and resembles fetal fat tissue. The solitary lipoblastoma is usually in the subcutaneous area and lipoblastomatosis may invade deep structures. Local recurrence may occur in 9% to 22% of patients especially in the diffuse subtype.
 
Fibrous hamartoma of infancy3 is a benign infiltrative lesion. It is a rapidly growing mass in the subcutaneous or dermis of the axillary fold, shoulder, arm, forearm, back, groin or thigh. It is characterised by well-defined fibrocollagenous tissue, small rounded primitive mesenchymal cells, and mature fat. Local excision is the treatment of choice. Recurrence is rare.
 
Lipofibromatosis,3 also known as non-desmoid-type infantile fibromatosis, is a very rare paediatric disease. To date, approximately only 60 cases have been reported. Typically, it is an ill-defined slow-growing tumour that presents as a painless lesion in the limbs. The rate of local recurrence is high. The regrowth and persistent disease rate is 72%.4 Fortunately, there is no known metastasis.
 
These four diagnoses differ quite significantly in prognosis and recommended management. In the present case, we advised conservative resection for histology, prognosis, management of disease progression, and treatment of the knee flexion contracture.
 
The diagnosis of a tumour in the neonatal period causes significant psychological distress to parents.5 Understanding the natural history and prognosis is the first step towards alleviating parental anxiety followed by inviting them to participate in the planning of future management. Sincere communication is an essential part of patient management. Sometimes professional intervention in the form of psychological support should also be considered.
 
Author contributions
All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.
 
Concept or design: YL Lam, WY Ho, R Yau, TWH Shek.
Acquisition of data: YL Lam, VWK Lee, TWH Shek.
Analysis or interpretation of data: YL Lam, VWK Lee, TWH Shek.
Drafting of the manuscript: YL Lam, TWH Shek.
Critical revision for important intellectual content: All authors.
 
Acknowledgement
We thank Ms Carol Anne Higgins for proofreading the manuscript.
 
Conflicts of interest
All authors have disclosed no conflicts of interest.
 
Funding/support
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
 
Ethics approval
This study was approved by the institutional review board (Ref. UW15/414).
 
References
1. Moore SW, Satgé D, Sasco AJ, Zimmermann A, Plaschkes J. The epidemiology of neonatal tumours, report of international working group. Pediatr Surg Int 2003;19:509-19. Crossref
2. Palumbo JS, Zwerdling T. Soft tissue sarcomas of infancy. Semin Perinatol 1999;23:299-309. Crossref
3. Fletcher CD, Bridge JA, Hogendoorn PC, Mertens F. WHO Classification of Tumours. Lyon: IARC; 2013.
4. Fetsch JF, Miettinen M, Laskin WB, Michal M, Enzinger FM. A clinicopathological study of 45 pediatric soft tissue tumors with an admixture of adipose tissue and fibroblastic elements, and a proposal for classification as lipofibromatosis. Am J Surg Pathol 2000;24:1491-500. Crossref
5. Orbach D, Sarnacki S, Brisse HJ, et al. Neonatal cancer. Lancet Oncol 2013;14:e609-20. Crossref

Candida glabrata chorioamnionitis and fungaemia complicating pregnancy following intrauterine insemination

DOI: 10.12809/hkmj164800
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
Candida glabrata chorioamnionitis and fungaemia complicating pregnancy following intrauterine insemination
Sofie SF Yung, FHKCOG, FHKAM (Obstetrics and Gynaecology)1; Maggie MC Cheng, FHKCOG, FHKAM (Obstetrics and Gynaecology)2; Paulin WS Ma, FHKCOG, FHKAM (Obstetrics and Gynaecology)2; PC Ho, MD, FHKAM (Obstetrics and Gynaecology)1
1 Department of Obstetrics and Gynaecology, The University of Hong Kong, Pokfulam, Hong Kong
2 Department of Obstetrics and Gynaecology, Queen Mary Hospital, Pokfulam, Hong Kong
 
Corresponding author: Dr Sofie SF Yung (ssfyung@hku.hk)
 
 Full paper in PDF
 
Introduction
Intrauterine insemination (IUI) is a fertility treatment that involves injection of a processed semen sample into the uterus via a transvaginal catheter after the cervix has been swabbed clean. Sterile instruments are used to reduce the risk of infection.
 
Historically, Candida glabrata has been considered a relatively non-pathogenic saprophyte of the normal flora of healthy individuals, rarely causing serious infections in humans. Contrary to the more common vaginal coloniser Candida albicans, C glabrata is unable to penetrate intact fetal membranes in vitro.1 This explains the rarity of C glabrata chorioamnionitis although it is a common vaginal coloniser found in up to 8% of pregnant women.1
 
The present study describes a rare case of C glabrata chorioamnionitis and fungaemia in a pregnancy following IUI.
 
Case presentation
A 32-year-old healthy primigravida with a trichorionic-triamniotic triplet pregnancy conceived by IUI presented in December 2011 to Queen Mary Hospital, Hong Kong at 16 weeks’ gestation with leaking of liquor. Physical examination and ultrasonography confirmed rupture of membranes of one of the triplets. The patient was initially treated with oral erythromycin but 2 days later she developed a fever of 39℃. Empirical intravenous broad-spectrum antibiotics were given for presumptive bacterial chorioamnionitis. In view of the poor prognosis at such an early gestation and the risk of maternal sepsis, medical abortion with misoprostol was considered appropriate. Complete abortion was achieved and the patient’s fever subsided the next day.
 
Two days after abortion, blood culture and vaginal swab test results revealed the presence of C glabrata. Intravenous anidulafungin 200 mg stat, then 100 mg every 24 hours was prescribed. The patient remained well and was discharged from the hospital after 2 weeks of antifungal treatment. Results from a second blood culture taken 3 days after abortion were negative.
 
In view of the rarity of fungaemia in immunocompetent hosts, testing for human immunodeficiency virus antibodies, lymphocyte subset and dihydrorhodamine reduction test was performed. All results were normal. Histological examination of the three placentae showed polymorph infiltration and presence of fungal spores, confirming acute fungal chorioamnionitis.
 
Discussion
To the best of our knowledge, this is the first report of C glabrata chorioamnionitis and fungaemia in a pregnancy following IUI. A search of the literature revealed 18 articles reporting 22 cases of C glabrata chorioamnionitis (online supplementary Appendix 1). Fifteen of the reported cases were associated with in-vitro fertilisation (IVF) and four with a foreign body (intrauterine contraceptive device or cervical cerclage). The growing number of reports may be partly due to improved diagnostic methods, but the increasing use of assisted reproductive technologies also appears to be an important factor. Contamination of the embryo by infected semen or the mother’s cervicovaginal Candida during transvaginal oocyte harvest, or direct inoculation of C glabrata into the uterus during embryo transfer are possible aetiological mechanisms.2 The only two reported cases of the rare Candida lusitaniae chorioamnionitis in the literature were also associated with IVF (online supplementary Appendix 2), further supporting the hypothesis.
 
Most of the reported cases were associated with preterm labour or preterm premature rupture of membranes (PPROM); therefore, it is also possible that intrauterine C glabrata infection was a result of ascending infection after PPROM and preterm labour, since assisted reproductive technologies are associated with multiple pregnancy, preterm labour, and PPROM. However, PPROM and preterm labour occur in about 6% of births and there have been only 23 reported cases (including the current report) of C glabrata chorioamnionitis. Sixteen of the 23 reported cases were associated with IVF and IUI. We conclude that C glabrata chorioamnionitis is more likely due to inoculation of the fungus into the uterus during IVF and IUI procedures, rather than a result of preterm labour and PPROM. The present case supports this hypothesis.
 
Although maternal outcome was good in the published cases, this fungal chorioamnionitis was often associated with poor fetal outcome. Only 30% (7 of 23 cases, including the present case) of the published affected pregnancies had any neonatal survival as they usually presented with PPROM or preterm labour in the second or early third trimester.
 
There are no guidelines for screening for vaginitis before assisted reproductive procedures. If asymptomatic C glabrata or other fungal colonisation is identified, there is no consensus on whether treatment should be given. One case of a successful IVF pregnancy following eradication of C glabrata by topical boric acid treatment had been preceded by an IVF pregnancy that ended in C glabrata sepsis and fetal loss.3 The authors suggested routine vaginal culture for yeast and treatment of positive culture results prior to embryo transfer, and commented that such an inexpensive test adds little to the overall costs and procedures associated with IVF.3 On the contrary, some authors suggest that a comprehensive screening programme may not be justified given the rarity of invasive disease despite widespread use of IVF and the relatively high rates of C glabrata carriage among pregnant women.2 The true incidence of C glabrata chorioamnionitis is unknown because it is likely to be underdiagnosed due to the difficulty in laboratory diagnosis.2 Treatment cost-effectiveness cannot be estimated, but the number needed to treat to prevent one C glabrata–related adverse outcome is likely to be large in view of the relatively high carrier rate and the rarity of C glabrata chorioamnionitis. Further research is needed to evaluate the cost-effectiveness of such a screen-and-treat programme before it can be recommended. In addition, there have been reports of emergence of antifungal resistance. If all asymptomatic carriers are treated prior to embryo transfer, emergence of drug resistance will become a concern. Similarly, whether it is worth screening men for any asymptomatic carriage is uncertain.
 
Conclusion
The possibility of C glabrata chorioamnionitis should be considered in pregnant women who develop chorioamnionitis after conceiving with assisted reproductive techniques. The reporting of this potentially devastating condition should be encouraged so as to improve our knowledge about its incidence, risk factors, pathogenesis, and management. Further research is needed to determine the incidence of fungal infection–related adverse outcomes and the cost-effectiveness of a screen-and-treat approach prior to assisted reproduction.
 
Author contributions
All authors contributed to the concept of the paper. SSF Yung, MMC Cheng, and PWS Ma contributed to the acquisition, analysis, and interpretation of data. SSF Yung drafted the article.
 
Declaration
All authors have disclosed no conflicts of interest. All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity. This paper was presented as a poster in the 25th Asian & Oceanic Congress of Obstetrics and Gynaecology (AOCOG), Hong Kong, on 15-18 June 2017.
 
References
1. Ganer Herman H, Mevorach Zussman N, Krajden Haratz K, Bar J, Sagiv R. Candida glabrata chorioamnionitis following in vitro fertilization: review of the literature. Gynecol Obstet Invest 2015;80:145-7. Crossref
2. Jackel D, Lai K. Candida glabrata sepsis associated with chorioamnionitis in an in vitro fertilization pregnancy: case report and review. Clin Infect Dis 2013;56:555-8. Crossref
3. Asemota OA, Nyirjesy P, Fox R, Sobel JD. Candida glabrata complicating in vitro pregnancy: successful management of subsequent pregnancy. Fertil Steril 2011;95:803.e1-2. Crossref

Endovascular treatment of erectile dysfunction due to internal iliac artery atherosclerotic disease

DOI: 10.12809/hkmj154810
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
Endovascular treatment of erectile dysfunction due to internal iliac artery atherosclerotic disease
Bryan P Yan, MB, BS, FRACP
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
 
Corresponding author: Dr Bryan P Yan (bryan.yan@cuhk.edu.hk)
 
 Full paper in PDF
 
Introduction
Erectile dysfunction (ED) is defined as the recurrent inability to achieve and maintain an erection satisfactory for sexual intercourse. Worldwide, ED affects approximately 300 million men, and nearly 30% of men between age 40 and 70 years.1 Current pharmacological options for treatment of ED are limited, with up to 50% of patients experiencing suboptimal response to oral phosphodiesterase inhibitor (PDE5i).2 Atherosclerotic occlusive disease of the ilio-pudendal-penile arteries resulting in arterial insufficiency to the penis has been reported to affect up to 75% of patients with ED.3 In a recent study of 30 diabetic patients with ED and coronary artery disease, significant internal iliac artery (IIA) and internal pudendal artery (IPA) disease was found 20% and 36.7% of patients, respectively.4 Atherosclerotic occlusive disease may result in arterial insufficiency to the penis, limiting the inflow of blood required to fill the corpora cavernosa to achieve penile erection. This report describes the case of a patient with ED caused by atherosclerotic disease of the left IIA that was successfully treated by endovascular revascularisation.
 
Case presentation
A 71-year-old man presented to our hospital with recurrent claudication and severe erectile dysfunction (ED). The patient had a history of insulin-requiring type 2 diabetes mellitus, hypertension, hyperlipidaemia, renal transplant for end-stage renal failure due to obstructive nephropathy, advanced coronary and peripheral artery disease status after multiple interventions. The patient had been diagnosed with ED more than 10 years previously. His ED responded initially to oral phosphodiesterase inhibitor (PDE5i) therapy. In the 12 months prior to the present case, the patient’s ED deteriorated and became refractory to PDE5i therapy. This caused significant distress and loss of quality of life because the patient wished to remain sexually active.
 
Peripheral angiography of the ilio-pudendal-penile arteries was performed opportunistically at time of endovascular intervention for recurrent lower limb claudication in September 2015. The peripheral angiography revealed total occlusion of the right IIA and haemodynamically significant stenoses in the left common and distal IIA with a significant pressure gradient of 20 mm Hg across the lesions (Fig 1). The penile artery and left IPA were supplied by the diseased left IIA. Elective endovascular intervention was performed via a 45-cm 6-Fr sheath inserted in the right common femoral artery and advanced over the aortic bifurcation to the left IIA. The IIA stenosis was dilated with a 4- × 40-mm balloon (Sterling; Boston Scientific, Marlborough [MA], United States) followed by a 5- × 40-mm paclitaxel-eluting balloon (Ranger; Boston Scientific) aiming to lower the risk of restenosis. The ostium of the left internal IIA was dilated with a 6- × 40-mm scoring balloon (Angiosculpt; AngioScore, Fremont [CA], United States) and the left common IIA was dilated with an 8- × 20-mm balloon (Sterling; Boston Scientific). Excellent angiographic results were achieved with elimination of the translesional gradient (Fig 2). There were no complications, and the patient was discharged the following day.
 

Figure 1. Angiography of the left ilio-pudendal-penile arterial system showing significant stenoses (white arrows) in the distal internal iliac artery (IIA) with a translesional gradient of 20 mm Hg. This resulted in poor distal flow into the internal pudendal artery (IPA) and inferior gluteal artery (IGA)
 

Figure 2. Excellent angiographic results post-angioplasty of the left internal iliac artery (IIA) using a drug-eluting balloon with resolution of translesional gradient. This resulted in improved distal flow into the internal pudendal artery (IPA) and inferior gluteal artery (IGA)
 
The patient reported significant improvement in erectile function at the 3-month follow-up visit. His erectile hardness score improved from 1 (the penis is larger than normal but not hard) to 3 (the penis is hard enough for penetration but not completely hard). Of the domains assessed by the international index of erectile function score: (i) erectile function improved from severe (score 1 out of 30) to moderate dysfunction (score 9); (ii) orgasmic function from severe (score 0 out of 10) to mild-to-moderate dysfunction (score 6); (iii) intercourse satisfaction from severe (score 0 out of 15) to moderate dysfunction (score 4), and (iv) overall satisfaction from moderate (score 4 out of 10) to mild dysfunction (score 8).
 
Discussion
With the advancement of endovascular techniques and technologies, revascularisation of the small-calibre penile artery (average 1-2 mm) and IPA (2-3 mm) has been shown to be safe, feasible, and associated with significant improvement in erectile function in selected ED patients with penile arterial insufficiency.5 6 In a study of 30 patients with ED and suboptimal response to PDE5i, percutaneous revascularisation of the IPA using coronary drug-eluting stents was associated with clinically meaningful improvement in ED.5 Another recently published study on pelvic revascularisation investigated 20 patients with arteriogenic ED.6 After balloon angioplasty for isolated penile artery stenosis, 60% of those patients demonstrated significant improvement in ED at 6 months.6 Drug-eluting balloons have been shown to be superior to plain balloon angioplasty in the treatment of infrainguinal peripheral arterial disease. However, the use of drug-eluting balloons in the IIA is an off-label indication and should be considered investigational.
 
In summary, endovascular treatment of ilio-pudendal-penile arterial disease may offer significant benefits in patients with ED associated with arterial insufficiency that is refractory to medical therapy. However, it is important to emphasise that there are many causes of ED and atherosclerotic disease of erectile-related arteries is only one of them. Close collaboration with a urologist and exclusion of other aetiologies of ED prior to angiography is critical in patient selection and successful outcome.
 
Author contributions
As an editor of the journal, BP Yan was not involved in the peer review process of the article. BP Yan contributed to performance of the procedure, drafting of the article, and critical revision of the content.
 
Declaration
The author has disclosed no conflicts of interest. The author had full access to the data, contributed to the study, approved the final version for publication, and takes responsibility for its accuracy and integrity.
 
References
1. NIH Consensus Conference. Impotence. NIH Consensus Development Panel on Impotence. JAMA 1993;270:83-90. Crossref
2. Hatzimouratidis K, Hatzichristou DG. A comparative review of the options for treatment of erectile dysfunction: which treatment for which patient? Drugs 2005;65:1621-50. Crossref
3. Philip F, Shishehbor MH, Desai MY, Schoenhagen P, Ellis S, Kapadia SR. Characterization of internal pudendal artery atherosclerosis using aortography and multi-detector computed angiography. Catheter Cardiovasc Interv 2013;82:E516-21. Crossref
4. Zaki H, Nammas W, Shawky A, Mortada A, Zaki T. Prevalence of internal pudendal artery disease in diabetic patients with erectile dysfunction and angiographically documented multi-vessel coronary artery disease. Egypt Heart J 2013;65:87-91. Crossref
5. Rogers JH, Goldstein I, Kandzari DE, et al. Zotarolimus-eluting peripheral stents for the treatment of erectile dysfunction in subjects with suboptimal response to phosphodiesterase-5 inhibitors. J Am Coll Cardiol 2012;60:2618-27. Crossref
6. Wang TD, Lee WJ, Yang SC, et al. Safety and six-month durability of angioplasty for isolated penile artery stenoses in patients with erectile dysfunction: a first-in-man study. EuroIntervention 2014;10:147-56. Crossref

Necrotising fasciitis: a rare complication of acute appendicitis

DOI: 10.12809/hkmj166180
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
Necrotising fasciitis: a rare complication of acute appendicitis
Thomas WY Chin, MB, ChB; Koel WS Ko, MB, BS; KH Tsang, MB, BS, FHKAM (Radiology)
Department of Radiology and Imaging, Queen Elizabeth Hospital, Yaumatei, Hong Kong
 
Corresponding author: Dr Thomas WY Chin (twychin@gmail.com)
 
 Full paper in PDF
 
Introduction
Acute appendicitis is a common surgical emergency that can cause severe complications if diagnosis and management are delayed.1 Necrotising fasciitis (NF) is a necrotic infection involving deeper layers of the skin and subcutaneous tissue that spreads rapidly along the fascia, progressing to systemic sepsis. It is most commonly induced by injury and is an extremely rare complication of acute appendicitis. In this article, we present a case of perforated appendicitis complicated by right thigh and scrotal NF. Since the condition runs a fulminant clinical course, prompt diagnosis and early surgical intervention are crucial to reduce mortality.
 
Case report
A 60-year-old man with good past health presented to the Accident and Emergency Department of Queen Elizabeth Hospital, Hong Kong, in December 2015 with a 6-day history of fever and lower abdominal pain.
 
His vital signs on presentation were as follows: systolic blood pressure 97 mm Hg; diastolic blood pressure 59 mm Hg; pulse 90 beats per minute; and body temperature 38.3°C. Physical examination revealed lower abdominal and right thigh tenderness without subcutaneous emphysema. Laboratory data showed leucocytosis (15.5 × 109/L) with neutrophilia (neutrophils 88.7%) and evidence of acute kidney injury (estimated glomerular filtration rate 38 mL/min/1.73 m2, serum creatinine 171 μmol/L).
 
Abdominal, pelvic, and right hip radiographs were unremarkable. Urgent abdominal and pelvic computed tomographic (CT) scan revealed a dilated retrocaecal appendix with heterogeneous wall enhancement, compatible with acute gangrenous appendicitis. There was rupture at the appendiceal tip, contiguous with a 2.8- × 4.5- × 8.0-cm gas-containing abscess posterolateral to the ascending colon and caecum (Fig 1). Increased peri-appendiceal and pericaecal stranding and free gas were noted. Multiple smaller pelvic abscesses were also observed. An incidental finding of abnormal swelling of the right upper thigh was noted in the limited coverage of the thigh in the original CT scan. Another CT scan including the whole right thigh was performed by the on-site radiologist. Abnormal high-density fluid and fat stranding were noted in the subcutaneous layer and intermuscular fascial planes in the anterior, adductor, and posterior compartments of the right thigh (Fig 2). The thigh muscles were swollen without discrete abscess formation. No gas density was detected along the fasciae. The initial overall imaging diagnosis was ruptured acute appendicitis with peri-appendiceal abscess, complicated by right thigh NF.
 

Figure 1. Coronal computed tomography image: dilated retrocaecal appendix with rupture at the tip (thick arrows). The appendiceal tip connected with a gas-containing abscess (thin arrow) posterolateral to the ascending colon. Abnormal fat stranding along the femoral neurovascular bundles (dashed arrows) is shown
 

Figure 2. Coronal computed tomographic image: generalised right thigh swelling. Abnormal high-density fluid and fat stranding in the subcutaneous layer (white thin arrow), intermuscular fascial planes (black arrow) and along the femoral neurovascular bundles (white thick arrow) are shown
 
Subsequent urgent laparotomy revealed a ruptured inflamed retrocaecal appendix and an 8-cm retrocolic abscess. Appendectomy and abscess drainage were performed. These were followed by exploration of the right thigh that revealed oedematous and necrotic subcutaneous and deep soft tissues mainly involving the adductor compartment. Multiple intramuscular abscesses were seen with turbid fluid tracing along the femoral neurovascular bundles proximally to the pelvic region. Overall features were compatible with NF. Right above-knee amputation with excisional debridement was performed in view of the patient’s poor general condition and extensive involvement.
 
Culture of the debrided muscle and fascial tissue yielded Escherichia coli, Bacteroides fragilis, and Streptococcus milleri. A combination of antibiotics was given, including amikacin, ampicillin, levofloxacin, linezolid, meropenem, and penicillin G. However, septic shock persisted with development of multi-organ dysfunction despite multiple inotropes. Another CT scan of the abdomen and pelvis was performed on postoperative day 1, revealing a grossly swollen scrotum with hydrocoele (not shown). No intrascrotal gas density was detected. In view of the patient’s clinical deterioration, urgent scrotal exploration was performed and revealed extensive scrotal skin necrosis with copious serous fluid draining from the perineum.
 
After the second surgery, the patient had persistent multi-organ failure with clinical deterioration despite supportive management. He developed acute respiratory distress syndrome with respiratory failure and disseminated intravascular coagulation with severe anaemia, further complicated by acute coronary syndrome. The patient succumbed on the fourth day of hospital admission.
 
Discussion
The incidence of NF has risen recently owing to an increased prevalence of patients who are immunocompromised secondary to diabetes mellitus or treatment for malignancy or human immunodeficiency virus infection.1 The mortality rate for NF is high, despite significant advances in antibiotic treatment, owing to its rapid progression to septic shock and multi-organ failure.1
 
Common causes of NF include minor trauma, skin infection, intravenous drug use, and surgical complication.1 The abdomen, groin, and extremities are the regions most commonly affected by NF.1 2 3 4 5 Necrotising fasciitis is commonly polymicrobial, caused by virulent toxin-producing bacteria such as Group A haemolytic streptococci and Staphylococcus aureus. Other causative bacteria include Bacteroides, Clostridium, Enterobacteriaceae, Peptostreptococcus, Proteus, Pseudomonas, and Klebsiella.1
 
The diagnosis of NF is challenging due to its rarity and non-specific presentation. Usually the early manifestations are local inflammatory signs and symptoms such as swelling, erythema, and tenderness, occasionally with fever. However, NF should be suspected when the severity of pain or clinical status are disproportional to local findings.5 Laboratory studies show leucocytosis with predominant neutrophilia,1 but is unfortunately non-specific.5 Presence of soft tissue gas in the absence of penetrating trauma suggests a diagnosis of NF,2 although the absence of soft tissue gas does not exclude the diagnosis, as evidenced by our case.
 
Plain radiographs are usually unhelpful for initial diagnosis as soft tissue gas is seldom detected until late in the disease process.1 Magnetic resonance imaging is superior in delineating soft tissue pathology but is a suboptimal modality for critically ill patients.2 Computed tomography is the preferred imaging modality, with reported findings including asymmetric fascial thickening with fat stranding and subcutaneous gas tracking along fascial planes.2 It also delineates the extent of tissue involvement well and is useful for monitoring treatment response.
 
Necrotising fasciitis secondary to perforated appendicitis is rarely reported. We have found only 18 case reports of NF caused by acute appendicitis published in the English literature.1 2 3 4 5 The affected regions included the abdominal wall (most commonly involved), perineum, and thigh. According to Taif and Alrawi,5 there have been only three reported cases of appendicitis complicated by NF predominantly involving the lower limb. All cases involved the right thigh, likely from more direct infective spread along the right femoral neurovascular bundles than the left.
 
Our case represents a rare but life-threatening consequence of a common disease despite the absence of risk factors. Early clinical changes of NF can be subtle. Early recognition, broad-spectrum antibiotic treatment, and aggressive surgical debridement are the cornerstones of management for this potentially lethal disease.1 A high index of suspicion is needed in diagnosis such that emergent surgical intervention can be initiated to improve clinical outcome.
 
Author contributions
All authors contributed to the design, acquisition and interpretation of data, drafting of the article, and critical revision for important intellectual content.
 
Acknowledgement
We would like to thank the staff radiographers of the Department of Radiology and Imaging, Queen Elizabeth Hospital for their assistance in acquisition of the images.
 
Declaration
All authors have disclosed no conflicts of interest. All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.
 
References
1. Chen CW, Hsiao CW, Wu CC, Jao SW, Lee TY, Kang JC. Necrotizing fasciitis due to acute perforated appendicitis: case report. J Emerg Med 2010;39:178-80. Crossref
2. Hung YC, Yang FS. Necrotizing fasciitis—a rare but severe complication of perforated appendicitis. Radiol Infect Dis 2015;2:81-3. Crossref
3. Hua J, Yao L, He ZG, Xu B, Song ZS. Necrotizing fasciitis caused by perforated appendicitis: a case report. Int J Clin Exp Pathol 2015;8:3334-8.
4. Wanis M, Nafie S, Mellon JK. A case of Fournier’s gangrene in a young immunocompetent male patient resulting from a delayed diagnosis of appendicitis. J Surg Case Rep 2016;2016:rjw058. Crossref
5. Taif S, Alrawi A. Missed acute appendicitis presenting as necrotising fasciitis of the thigh. BMJ Case Rep 2014;2014:bcr2014204247. Crossref

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