A 59-year-old woman had inoperable carcinoma of the upper oesophagus and had undergone chemoradiotherapy and immunotherapy. A covered oesophageal stent (Niti-S, 20 mm in diameter, 80 mm in length; Taewoong Medical, South Korea) was inserted in August 2021 to manage a tracheoesophageal fistula. The proximal end of the stent was located just distal to the cricopharyngeal constriction. Five months after stent placement, the patient developed erosions at the proximal and distal ends of the stent into the trachea and bronchi, respectively. A covered tracheal stent (AERO, 18 mm in diameter, 40 mm in length; Merit Medical, South Jordan [UT], US) and a distal extension with a covered oesophageal stent (Niti-S) were inserted on two separate occasions.

The patient presented to the emergency department 7 months after initial oesophageal stent insertion with haemoptysis. Her haemoglobin level had fallen to 6.3 g/dL and she developed hypotension and desaturation requiring intubation and admission to the intensive care unit. Upper endoscopy revealed blood clots over the proximal part of the oesophagus but no active bleeding following clot removal. Computed tomography showed no contrast extravasation. The upper end of the oesophageal stent was close to the left common carotid artery. A small suspicious outpouching of the artery was also seen at that location (Fig 1a and 1b).

Surgery was performed under general anaesthesia via a left neck incision. Retrograde puncture of the left common carotid artery was performed and an 8-Fr vascular sheath (AVANTI+; Cordis, Miami Lakes [FL], US) was placed. Digital subtraction angiogram revealed a small pseudoaneurysm confirming our clinical suspicion (Fig 1c). Oesophageal stent erosion was suspected to be the cause due to its proximity. Complete exclusion of the pseudoaneurysm was achieved (Fig 2) using a covered vascular stent (Covera Plus, 8 mm in diameter, 60 mm in length; Becton, Dickinson and Company, Franklin Lakes [NJ], US).

Postoperatively, the patient’s condition improved with no rebleeding. She refused further surgery to repair the fistula via a manubrial resection. Further covered tracheal stenting (Dumon Y, 15 mm in diameter; Boston Medical Products Inc, Shrewsbury [MA], US) was performed to exclude residual tracheoesophageal fistula and prevent aspiration pneumonia. The patient was prescribed long-term moxifloxacin because of the potential communication with the aerodigestive tract and contamination. She was well 6 weeks later. Reassessment computed tomography showed a patent carotid stent with no features of stent infection and no residual pseudoaneurysm.

Upper gastrointestinal bleeding is a frequent presentation following oesophageal stenting. Endoscopy has both diagnostic and therapeutic roles in common bleeding pathologies such as tumour and peptic ulcer. The presence of a stent often makes identification of a bleeding site difficult. Diagnosing fistulation with major arteries requires a high level of suspicion, especially if the bleeding is extensive.

Although it is tempting to remove a blood clot during endoscopy, care should be exercised to avoid rupture of any underlying pseudoaneurysm with consequent torrential bleeding. Endoscopic biopsy of tissue around the oesophageal stent can also lead to pseudoaneurysm rupture as reported in an early case report by Kohl et al.1

Computed tomography is often useful to show the site of bleeding and corresponding anatomical relationship. Nonetheless a negative imaging may provide false reassurance. The pseudoaneurysm may be small because of impingement by the pointed oesophageal stent struts. This can be missed if the slice thickness of scan is not thin enough. Three-dimensional reconstruction images may provide more information. An on-table angiogram should be considered when the diagnosis is in doubt.

Fistulation of the carotid artery by a metallic oesophageal stent is rare and was first reported in 2001.1 Four previously reported cases were found in the literature.1 2 3 4 Among these cases, three adult patients had complications of previous treatments for carcinoma in the head and neck region, where two had oesophageal stricture1 3 and one had a tracheoesophageal fistula2; another 4-year-old paediatric patient had an oesophageal stent inserted for anastomotic stricture following surgical repair of oesophageal atresia.4

In Kohl et al’s report,1 resection was performed with a bypass using homograft made from the ascending aorta to the carotid bifurcation. Asymptomatic blockage of the graft was found soon after the procedure. The patient died of rebleeding 2 months later. Ali et al2 used endovascular coiling of pseudoaneurysm and stenting with a self-expandable nitinol stent. The patient had a rebleed 2 weeks later that required placement of a covered vascular stent. Staged open ligation of the common carotid artery was performed as a definitive treatment.2

A complete endovascular approach has been reported more recently. One patient received stenting to control bleeding and a staged operation to sacrifice the common carotid artery by endovascular coiling, but the long-term outcome was not reported.3 The paediatric patient was successfully treated with repeated coiling of the pseudoaneurysm and stenting with a bare-metal stent. He remained asymptomatic at a follow-up 1 year later.4

Endovascular treatment acted as a bridge to definitive management if quick open access is difficult due to anatomical constraints, as in our patient. Balloon occlusion test and cerebral perfusion scan can confirm adequate collateral supply before carrying out a second-stage operation to sacrifice the common carotid artery.2 3

The two major concerns with this temporising treatment are the risks of rebleeding and endograft infection. Definitive management should include surgical separation of the fistula. The oesophageal defect can be repaired primarily with or without reinforcement using diaphragm, intercostal muscle, serratus muscle, or omentum. Oesophagectomy or diversion are the other options if primary repair is not possible.

The diseased artery can be too friable for primary repair. Open ligation and endovascular coiling of the proximal carotid artery can be considered to prevent rebleeding provided an adequate collateral supply to the brain is confirmed.2 3 Revascularisation can be performed if required using bypass grafts from the aorta or subclavian artery. Operative risks include stroke, graft thrombosis and graft infection, especially when the surgical field is contaminated.

Similar fistulation between an aberrant right subclavian artery and oesophagus has been reported following oesophageal stent placement due to the anatomical relationship. Experience shows that most cases required immediate open surgery followed by tamponade using a hydrostatic dilator or Sengstaken–Blakemore tube. Surgery can be performed via a median sternotomy, thoracotomy or a manubrial resection. In patients with endovascular stenting as a temporising measure, the stent should be removed at the time of surgery to prevent oesophageal pressure necrosis due to a ‘sandwich effect’ with the oesophageal stent.5

For patients in whom definitive treatment is not possible, removal of an oesophageal stent can promote fistula healing. Proximal extension of a covered oesophageal stent may also minimise contamination from the aerodigestive tract. Long-term prophylactic antibiotics should be given but efficacy is not guaranteed. Alternatively, sacrificing unilateral carotid artery via an endovascular technique such as coils or plugs may prevent rebleeding. There is nonetheless no long-term evidence to support this technique.

All authors contributed to the concept or design of the study, acquisition of the data, analysis or interpretation of the data, drafting of the manuscript, and critical revision of the manuscript 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.

All authors have disclosed no conflicts of interest.

This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

The patient was treated in accordance with the Declaration of Helsinki and provided written informed consent for all treatment and procedures and for publication of this case report.

1. Kohl O, Rauber K, Doppl W. Perforation of an esophageal stent into the common carotid artery. Gastrointest Endosc 2001;53:374-8. Crossref

2. Ali AT, Kokoska MS, Erdem E, Eidt JF. Esophageal stent erosion into the common carotid artery. Vasc Endovascular Surg 2007;41:80-2. Crossref

3. Yadam S, Rali P, Balaan M, Lega M. A case of carotid-esophageal fistula masquerading as an upper gastrointestinal bleed. Am J Respir Crit Care Med 2016;194:e2-3. Crossref

4. Fachin CG, Demartini Z Jr, Pinto AS, et al. Carotidesophageal fistula treated by endovascular approach. Vasc Endovascular Surg 2021;55:419-21. Crossref

5. Merlo A, Farber M, Ohana E, Pascarella L, Crowner J, Long J. Aberrant right subclavian artery to esophageal fistula: a rare case and its management. Ann Thorac Surg 2020;110:e85-6. Crossref

A 53-year-old man from northwest Tamil Nadu, India presented to our institution in January 2021 with a 3-month history of new-onset phimosis with swelling of the glans and an ulcer and penile discharge. The lesion presented initially with seropurulent discharge from the preputial sac. The patient later noticed some induration over the dorsal aspect that progressed further to an ulcer with frank purulent discharge. He had no family history of tuberculosis (TB) and no venereal disease or significant past surgical intervention. He had type 2 diabetes mellitus controlled by regular medication. His spouse had no significant history of pelvic inflammatory disease or secondary infertility and no present complaint of vaginal discharge, lower abdominal pain or productive cough.

On examination, the patient was of average built and nourishment. Vital signs were stable and examination of the respiratory, cardiovascular and gastrointestinal systems was unremarkable. Local examination of the external genitalia revealed staining of garments, phimosis, and an ulcer of 1×1 cm in size over the dorsal aspect of the penis with foul smelling purulent discharge near the corona. The glans palpable through the prepuce was hard in consistency and non-tender. The penile shaft was indurated up to the base and non-tender. There was no significant inguinal lymphadenopathy. Testes, spermatic cord and scrotum were clinically normal.

Blood investigations revealed haemoglobin level of 13.1 g/dL, white blood cell count of 6900/mm³, neutrophil level of 60%, platelet count of 234 000/μL, and glycated haemoglobin level of 7.8%; serology showed that human immunodeficiency virus, hepatitis B surface antigen and syphilis were non-reactive. Ultrasound of bilateral groin revealed a few inguinal nodes bilaterally, with the largest on the right measuring 8.7 mm. All nodes showed preserved fatty hilum and normal vascularity.

With the clinical diagnosis of localised carcinoma penis in mind, the patient was counselled about the need for intervention in the form of penile biopsy followed by total amputation of the penis with perineal urethrostomy. Under spinal anaesthesia, a dorsal slit was made in the penis that revealed penile oedema with purulent discharge from the preputial edge, multiple small granulomas and a hard and purulent cover over the glans. The glans penis was partially necrosed but the meatus was preserved. On extension of the dorsal slit to the base, the shaft was found to be covered in pus and slough with a hard consistency of the corpora cavernosa. Penile biopsy was taken from the glans and shaft. The slit cut surface was approximated at the base and haemostatic sutures placed over the glans to let the wound drain. A 16-Fr catheter was passed. Postoperatively, the patient was started on 4.5-g piperacillin sodium and tazobactam sodium via intravenous route three times a day. His postoperative course was uneventful with the wound showing purulent discharge, managed with twice daily saline dressings. The possibility of infectious origin of the disease was discussed with the patient.

After discussion with the pathologist, a provisional report was obtained of granulomatous inflammation with a few areas of necrosis. The need for culture and sensitivity was discussed with the patient, but due to financial constraints the patient was unwilling to proceed. He was initiated on anti-tubercular therapy as per regional antimicrobial policy. The final histopathology confirmed necrotising and granulomatous inflammation, with no acid-fast bacilli noted.

The patient and his partner were screened for pulmonary and genitourinary TB after the final histopathology report. The patient was discharged on postoperative day 9 with instructions to continue ATT for 6 months. He was advised to attend a local clinic for dressing changes every week until the wound had healed. The wound showed signs of healing on follow-up (Fig 1). After 6 weeks there were signs of build-up of slough. At 8 weeks, after completion of the intensive phase, the patient was referred for local surgical debridement and wound closure due to build-up of slough over the wound surface. He completed the course of ATT and the wound healed well (Fig 2). He has since developed erectile dysfunction, probably owing to secondary fibrosis of the corpora cavernosa. He does not desire treatment at this time.

Genitourinary TB is the most common form of extrapulmonary TB, but penile presentation is one of the least common forms of genitourinary TB (<1%).1 The epididymis (42%) followed by seminal vesicle (23%), prostate (21%), testis (15%) and vas deferens (12%) are common sites of presentation.2 In its primary form, local spread of bacilli from clothing, ejaculation, endometrial secretions, circumcision, and intravesical Bacillus Calmette–Guérin has been reported.2 The secondary form arises due to the subsequent complication of lung TB or TB in other parts of the urogenital tract, extending through the urethra or via a haematogenous route.

Tuberculosis of penis may affect the skin, glans penis or cavernous bodies. It can mimic penile carcinoma in presentation, much like our patient. Tuberculosis affecting the glans penis can present as tuberculous chancre, papulo-necrotic tuberculoid, TB cutis orificialis or tuberculous gumma. In most cases, the lesion takes the form of an ulcer that is difficult to differentiate from a malignant tumour. The lesion can be extensive, with involvement of the urethra and corpus cavernosum. Since young adults are affected, their partner should always be evaluated for genital TB.3 Although there are several tests for diagnosis of TB, biopsy remains confirmatory. Surgical management may be required in doubtful cases in spite of successful treatment with ATT. Organ sparing surgery coupled with ATT should be the goal of treatment.4

Our experience highlights the similarities in presentation of penile carcinoma and primary penile TB, further cementing the need for a dorsal slit prior to definitive procedure. A high index of suspicion should be maintained considering the endemic status of TB in South-East Asian countries. Biopsy should always be performed in doubtful cases.

Concept or design: A Sharma.
Acquisition of data: All authors.
Analysis or interpretation of data: All authors.
Drafting of the manuscript: A Sharma.
Critical revision of the manuscript for important intellectual content: All authors.

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.

All authors have disclosed no conflicts of interest.

This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

The patient was treated in accordance with the Declaration of Helsinki. Written informed consent was obtained from the patient for publishing of data relevant to the case report.

1. Nimisha E, Gupta G. Penile lupus vulgaris: a rare presentation of primary cutaneous tuberculosis. Int J STD AIDS 2014;25:969-70. Crossref

2. Amir-Zargar MA, Yavangi M, Ja’fari M, Mohseni MJ. Primary tuberculosis of glans penis: a case report. Urol J 2004;1:278-9.

3. Gangalakshmi C, Sankarmahalingam. Tuberculosis of glans penis—a rare presentation. J Clin Diagn Res 2016;10:PD05-6. Crossref

4. Rajeev TP, Pranab KR, Phukan PK, Baruna SK, Das Roop R. Tuberculosis of penis mimicking an advanced penile cancer—a case report. Int J Sci Res 2018;7:16-7.

In January 2015, a 36-year-old man with good past health presented to a hospital in Hong Kong with intermittent low-grade fever and left knee effusion. Physical examination revealed mild effusion, erythema, warmth and tenderness over the left knee, with 10˚ flexion contracture and flexion range up to only 70˚. The levels of inflammatory markers (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR], and antinuclear antibodies [ANA]) were elevated. Single-attempt arthrocentesis on the affected knee yielded 1 mL of yellow fluid, subsequently negative for Gram stain and culture only. No obvious abnormalities were observed on plain radiograph (Fig 1a), but magnetic resonance imaging (MRI) in June 2015 demonstrated synovial thickening, bone marrow oedema and subtle cortical erosion at the lateral femoral condyle (Fig 1b). Infection could not be excluded. Non-steroidal anti-inflammatory drugs were prescribed for symptomatic control. The recurrent left knee effusion persisted despite treatment, but no further attempts at arthrocentesis were made until 2018.

In view of the joint stiffness, recurrent knee effusion and persistently elevated levels of inflammatory markers, the patient was referred to a rheumatologist. A working diagnosis of atypical rheumatoid arthritis (RA) was made despite negative testing of anticyclic citrullinated peptide antibody and rheumatoid factor. Sulphasalazine was started in September 2015. Due to persistent knee inflammation, intraarticular steroid injection was given in November 2015 with limited effect. Methotrexate and leflunomide were prescribed in escalating doses. The patient was simultaneously followed up by the orthopaedic department where analgesics and physiotherapy were prescribed. Interval MRI in December 2017 showed diffuse synovial thickening, multifocal erosive changes and bone marrow oedema in the proximal tibia, reported to be in keeping with RA. Due to progressive worsening of his knee, the patient attended the private sector and was prescribed golimumab biologics in February 2018.

In April 2018, a cystic swelling developed over the posterolateral aspect of his left knee. Results of aspiration yielded a positive acid-fast bacilli smear and rapid cultures via Mycobacteria Growth Indicator Tube grew Mycobacterium tuberculosis. Knee X-ray revealed complete erosion of the medial and lateral tibiofemoral joints (Fig 1c) while MRI showed synovial thickening and intraosseous collection over the medial and lateral tibia (Fig 1d and e). Disease-modifying antirheumatic drugs were discontinued and the patient commenced a 9-month course of antituberculous drugs, namely isoniazid, rifampicin, ethambutol, pyrazinamide, and pyridoxine.

Despite eventually controlling the tuberculosis (TB), the patient’s knee function deteriorated and he was referred to a tertiary hospital for consideration of total knee arthroplasty (TKA). Preoperative assessment revealed 60˚ ankylosis of the left knee (Fig 2a) and healed sinus tracts without signs of residual infection. Preoperative investigations revealed normal ESR and CRP levels. Robotic arm–assisted TKA with varus-valgus constrained insert (Fig 1f) was performed in March 2020 and the patient was prescribed a 12-month course of antituberculous chemotherapy postoperatively. Postoperative range of motion (ROM) was 0˚ to 70˚ with 10˚ extension lag at 6 weeks due to quadriceps atrophy. Manipulation under anaesthesia was performed 3 months postoperatively to enhance flexion range. A final ROM was of 0˚ to 95˚ was achieved with no residual extension lag (Fig 2b and c). The latest follow-up 1.5 years postoperatively showed stable ROM with no signs of reinfection. The patient could walk unaided.

Tuberculosis of the knee is a rare form of osteoarticular TB that is prone to misdiagnosis due to its nonspecific presentation. It has an indolent course compared with bacterial septic arthritis. The clinical, radiological and laboratory features mimic inflammatory arthritis such as RA. Both diseases can present with monoarticular joint pain, erythema, swelling, and stiffness. In knee TB, the Phemister triad of juxta-articular osteopenia, joint space narrowing and peripheral bone erosions can be observed on plain radiographs, but these can also be evident in RA. Magnetic resonance imaging features of TB include multifocal bone erosions, articular surface destruction, cartilage erosions, and marrow oedema.1 Similar laboratory results include elevated white cell count (WCC) and percentage of polymorphonuclear neutrophils (PMNs) in blood and synovial fluid, and sustained elevation of ESR, CRP and anti-nuclear antibody levels due to active inflammation.

As in all circumstances of suspected infection, a patient’s symptoms and risk factors such as diabetes mellitus, RA and prior surgery should be assessed.2 Local skin condition, effusion and ROM should be noted on physical examination. Synovial fluid from arthrocentesis should be sent for total and differential cell counts, biochemistry, microbiology, crystals, and cytology. Total and differential counts are helpful in differentiating infective and inflammatory causes. Synovial fluid with WCC of >50 000/mm³ and PMN level of >75% point towards acute septic arthritis, while WCC of 2000 to 100 000/mm³ and PMN level of >50% suggest inflammatory arthritis.3 Nonetheless in TB, the WCC is typically in the inflammatory range of 10 000 to 20 000/mm.3 4 Joint aspirate should be sent for fungal and acid-fast bacilli smear, culture and TB–polymerase chain reaction (TB-PCR) to identify atypical organisms in refractory patients. Although the high specificity and shorter turnaround time of TB-PCR can complement cultures and help achieve an early diagnosis of TB, culture remains the gold standard to exclude TB infection due to its higher sensitivity. When synovial fluid aspirate is inadequate, repeated aspiration or even arthroscopic synovial biopsy should be considered. Autoimmune markers should be determined to exclude an autoimmune cause. Serial knee X-rays and MRIs should be taken regularly to monitor disease progression. In equivocal cases, arthroscopic synovial biopsy can be performed. A typical histological finding of caseating granuloma with lymphocytic infiltration is diagnostic of TB. Although arthrocentesis is less invasive, it has a lower diagnostic sensitivity (80%) for knee TB than synovial biopsy (90%).4

Tuberculosis of the knee can be managed conservatively by 12 to 18 months of antituberculous chemotherapy if identified early. With increasing joint damage, surgical intervention including debridement, synovectomy and arthroplasty might be necessary. The long disease course of joint destruction leads to fibrosis and ankylosis of the knee joint. Total knee arthroplasty is regarded as a primary treatment for advanced TB of the knee. Sultan et al5 suggest TKA be performed 1 to 5 years following eradication of TB to minimise reinfection risk. Postoperatively, 12 to 18 months of antituberculous drug therapy is believed to be highly effective in preventing recurrent infection, possibly due to the biofilm-lacking nature and poor metal adherence of TB.5

Robotic arm–assisted TKA with varus-valgus constrained insert was performed for our patient. The use of a constrained implant facilitated greater coronal plane stability in view of the extensive bone loss, ankylosis and ligamentous laxity secondary to prolonged TB infection. Robotic arm–assisted TKA was adopted since it enables higher accuracy in bone cutting and implant positioning than manual TKA.6 This is important for a patient receiving TKA at a young age.

Tuberculosis of knee is rarely documented in Hong Kong. This case highlights the importance of recognising TB as an important differential diagnosis of inflammatory arthritis. Maintaining a high index of suspicion will facilitate early diagnosis, potentially sparing the patient from joint destruction and TKA at a young age. In the event of recurrent knee effusion, synovial fluid samples should be sent for TB-PCR in addition to cell count, cytology, bacterial, acid-fast bacilli smear and cultures. Total knee arthroplasty plays a significant role in restoration of acceptable ROM in a knee with extensive bone erosion and ankylosis.

Concept or design: All authors.
Acquisition of data: All authors.
Analysis or interpretation of data: All authors.
Drafting of the manuscript: HMH Chan, H Fu.
Critical revision of the manuscript for important intellectual content: H Fu, KY Chiu.

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.

All authors have disclosed no conflicts of interest.

This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

The patient was treated in accordance with the Declaration of Helsinki and provided consent for publication of this case report.

1. Choi JA, Koh SH, Hong SH, Koh YH, Choi JY, Kang HS. Rheumatoid arthritis and tuberculous arthritis: differentiating MRI features. AJR Am J Roentgenol 2009;193:1347-53. Crossref

2. Margaretten ME, Kohlwes J, Moore D, Bent S. Does this adult patient have septic arthritis? JAMA 2007;297:1478-88. Crossref

3. Horowitz DL, Katzap E, Horowitz S, Barilla-LaBarca ML. Approach to septic arthritis. Am Fam Physician 2011;84:653-60.

4. Wallace R, Cohen AS. Tuberculous arthritis: a report of two cases with review of biopsy and synovial fluid findings. Am J Med 1976;61:277-82. Crossref

5. Sultan AA, Cantrell WA, Rose E, et al. Total knee arthroplasty in the face of a previous tuberculosis infection of the knee: what do we know in 2018? Expert Rev Med Devices 2018;15:717-24. Crossref

6. Hampp EL, Chughtai M, Scholl LY, et al. Robotic-arm assisted total knee arthroplasty demonstrated greater accuracy and precision to plan compared with manual techniques. J Knee Surg 2019;32:239-50. Crossref

In August 2017, a 59-year-old male with good past health was admitted via the emergency department with a 4-day history of abdominal distension and epigastric pain. He had passed no stool for 2 days. Physical examination revealed epigastric tenderness and an empty rectum. Abdominal X-ray showed intestinal obstruction and erect chest X-ray showed no free gas under the diaphragm. Blood tests on admission revealed a normal complete blood count and acute renal failure (Table). The patient was started on intravenous (IV) fluid and IV amoxicillin and clavulanate. Urgent computed tomography (CT) abdomen and pelvis with contrast showed acute appendicitis with perforation and dilated small bowel without an obvious transition point. Emergency laparotomy revealed appendiceal diverticulitis with walled-off localised abscess formation around the appendix. The base of the appendix was healthy. Microscopic examination of the appendix showed dense mixed inflammatory cell infiltration in periappendiceal fat and serositis, with no evidence of malignancy, thrombosis or ischaemia.

Three days postoperatively, the patient developed fever and hypotension and was given IV piperacillin and tazobactam. There was no organomegaly, lymphadenopathy or skin lesions on physical examination. He became dull looking but there was no focal neurological deficit. Septic workups with blood and urine were negative. Sputum culture showed Enterobacter cloacae, resistant to amoxicillin and clavulanate. Widal test, Weil–Felix test, human immunodeficiency virus serology and tests for viral hepatitis were all negative. A second abdomen CT showed no gross infective foci and only a few subcentimetre lymph nodes. Plain brain CT showed no focal intracranial lesions. Blood tests showed a leukoerythroblastic blood picture and no circulating abnormal cells, and acute hepatic and renal failure with markedly elevated lactate dehydrogenase level (Table). Fever did not abate despite IV piperacillin and tazobactam, IV meropenem and IV anidulafungin were prescribed for support. In the second week postoperatively, blood tests showed progressive anaemia and thrombocytopenia with microangiopathic haemolytic anaemia (MAHA) and a leukoerythroblastic blood picture (Table and Fig a). Ferritin and triglyceride levels were markedly elevated.

Bone marrow biopsy was subsequently performed and revealed many abnormal pleomorphic large cells and haemophagocytosis (Fig). In view of the fever of unknown origin, cytopenia, hypertriglyceridaemia, markedly elevated ferritin and haemophagocytosis in the bone marrow, a diagnosis was reached of haemophagocytic lymphohistiocytosis (HLH) and dexamethasone 15 mg daily orally and IV immunoglobulin started. Trephine biopsy showed prominent infiltration of pleomorphic large cells in focal linear profiling and intrasinusoidal clusters. With immunohistochemistry, the large cells were shown to be positive for the markers cluster of differentiation (CD20) [Fig e], CD30, CD5, and negative for activin receptor-like kinase 1 and cyclin D1. Epstein-Barr virus–encoded small RNA in situ hybridisation was negative. A diagnosis was made of intravascular large B-cell lymphoma (IVLBCL).

The ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity, antigen and autoantibody assays were performed. There was severe reduction in ADAMTS13 activity to 5% with ADAMTS13 antigen level moderately reduced to 215 ng/mL (reference range: 430-970) and autoantibody level at 2.5 units/mL (negative: <15). This confirmed ADAMTS13 deficiency and functional defect compatible with the picture of malignancy-associated thrombotic thrombocytopenic purpura (TTP). The patient was prescribed immunochemotherapy with rituximab (recombinant anti-CD20), cyclophosphamide, vincristine and prednisolone, and rasburicase for prophylaxis of tumour lysis syndrome. Hydroxydaunorubicin was added in the second cycle of immunochemotherapy (R-CHOP, ie, a combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) after which blood counts and liver and renal function test results markedly improved (Table). The patient was in complete remission after six cycles of R-CHOP. Nonetheless he died of inoperable squamous cell carcinoma of oesophagus 3 years after the diagnosis of lymphoma.

Intravascular large B-cell lymphoma is a rare subtype of extranodal large B-cell lymphoma characterised by selective growth of neoplastic cells inside the lumina of small- and medium-sized vessels, often with an aggressive clinical course. There are two major patterns of clinical presentation: the classic form with neurocutaneous involvement and the haemophagocytic syndrome–associated form with multiorgan failure, hepatosplenomegaly, and pancytopenia. Diagnosis of IVLBCL is challenging due to its variable presentation. Imaging may be negative due to the lack of detectable tumour masses.

The initial presentation of this patient was atypical, with appendiceal diverticulitis and perforation. Review of the appendix specimen confirmed the absence of lymphoma involvement. There was no hepatosplenomegaly. The abrupt onset of anaemia and thrombocytopenia with MAHA raised the possibility of postoperative TTP. Patients with postoperative TTP characteristically have a normal complete blood count prior to surgery, but subsequently show MAHA with thrombocytopenia about 5 to 9 days after surgery.1 Fever, renal impairment, and neurological symptoms are variably present. Nonetheless the abundance of schistocytes and nucleated red cells in the blood film and acute liver failure did not support a diagnosis of postoperative TTP, warranting further investigations.

Neoplastic cells may cause endothelial damage and result in release of ultra-large von Willebrand factor multimers. Autoantibodies against ADAMTS13 may also play a role in pathogenesis, leading to platelet activation and thrombotic microangiopathy.2 In our case, ADAMTS13 activity was markedly reduced at 5%, unusually low for malignancy-associated TTP (median ADAMTS13 activity: 50%).3 Some secondary TTP cases have been reported with markedly reduced ADAMTS13 activity4 but the significance is uncertain. The ADAMTS13 activity was also disproportionately lower than the antigen level, indicating a functional defect that may be seen in acquired TTP. Negative autoantibody against ADAMTS13 suggests against a diagnosis of idiopathic TTP. Distinguishing malignancy-associated TTP from idiopathic or postoperative TTP is important since therapeutic plasma exchange is effective in idiopathic or postoperative TTP but not in malignancy-associated TTP.

Although the anaemia and thrombocytopenia could be explained by the MAHA, hyperferritinaemia, hypertriglyceridaemia and haemophagocytosis in bone marrow were compatible with HLH. Of note, the current diagnostic criteria for HLH were originally proposed for diagnosis in paediatric patients.5 Criteria cut-offs such as a ferritin level >500 ng/mL may not be applicable in adults where there are many other reasons for such a high level. Bone marrow biopsy is the preferred investigation in the diagnosis of HLH and IVLBCL. A high index of suspicion should be maintained since the peripheral blood may not show abnormalities specific to these diagnoses.

Concept or design: All authors.
Acquisition of data: All authors.
Analysis or interpretation of data: All authors.
Drafting of the manuscript: WK Lam.
Critical revision of the manuscript for important intellectual content: WK Lam, ESK Ma, SF Yip.

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.

All authors have disclosed no conflicts of interest.

This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

The patient was treated in accordance with the Declaration of Helsinki and has provided informed consent for all treatments and procedures, and consent for publication.

1. Eskazan AE, Buyuktas D, Soysal T. Postoperative thrombotic thrombocytopenic purpura. Surg Today 2015;45:8-16. Crossref

2. Sill H, Höfler G, Kaufmann P, et al. Angiotropic large cell lymphoma presenting as thrombotic microangiopathy (thrombotic thrombocytopenic purpura). Cancer 1995;75:1167-70. Crossref

3. George JN. Systemic malignancies as a cause of unexpected microangiopathic hemolytic anemia and thrombocytopenia. Oncology (Williston Park) 2011;25:908-14.

4. Hassan S, Westwood JP, Ellis D, et al. The utility of ADAMTS13 in differentiating TTP from other acute thrombotic microangiopathies: results from the UK TTP Registry. Br J Haematol 2015;171:830-5. Crossref

5. Henter JI, Horne A, Aricó M, et al. HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 2007;48:124-31. Crossref

A 40-year-old man presented with right upper lid swelling for several months. There was no pain or redness. He had received radiotherapy for nasopharyngeal carcinoma 12 years ago. The swelling did not respond to antibiotics nor non-steroidal anti-inflammatory medication. On examination, there was mechanical ptosis and loss of skin crease. The marginal reflex distance, palpebral fissure height (PFH), and levator function on the right eye were 2 mm, 8 mm, and 8 mm, respectively. Extraocular movement was normal and there was no proptosis (Fig 1a).

The diagnosis was periocular lymphoedema affecting mainly the right upper lid. He underwent right upper lid blepharoplasty, levator resection with biopsy, debulking of orbital septum, preseptal tissues and preaponeurotic fat pad, and lid crease formation under local anaesthesia. Histological examination revealed skin, adipose tissue and fibrovascular tissue with no evidence of malignancy. Postoperatively, there was significant improvement in symptoms and cosmesis (Fig 1b) and no recurrence after 9 months.

A 57-year-old woman underwent left hemiglossectomy and adjuvant radiotherapy for carcinoma of tongue. She presented with gradual swelling of the left upper lid causing visual obstruction. Examination revealed left upper lid swelling with secondary mechanical ptosis (Fig 2a). Her marginal reflex distance PFH, and levator function on the left eye were 0 mm, 4 mm, and 9 mm, respectively. There was also left hemifacial swelling. Visual acuity, intraocular pressure, fundal and pupil examination, and extraocular movement were all normal. There were no signs of recurrent carcinoma of tongue and no palpable cervical lymph nodes.

Similar to Case 1, surgical correction of eyelid lymphoedema was performed. Postoperatively, lid swelling resolved with reformation of lid crease (Fig 2b). The patient remained well 4 years after the surgery with no recurrence.

A 71-year-old man received radiotherapy for nasopharyngeal carcinoma in 1982. He presented with persistent non-pitting left upper lid swelling for 20 years. Incisional biopsy performed in 2004 revealed non-specific changes with no malignant cells. Additional eyelid surgery was offered but the patient opted for conservative management. Interval computed tomography imaging showed left eyelid swelling with no retrobulbar mass, and rectus muscles were not thickened. Examination revealed left upper lid swelling with secondary mechanical ptosis and loss of lid crease. Marginal reflex distance, PFH, and levator function on the left eye were 0 mm, 1 mm, and 5 mm, respectively. Extraocular movement and other physical examinations were normal.

Due to persistent symptoms, the patient elected surgical correction of eyelid lymphoedema. Biopsy showed no signs of malignancy. Postoperatively, left upper lid swelling resolved. The patient remained well 3 years postoperatively with no recurrence.

A 65-year-old woman presented with persistent right upper lid swelling in 2008. She had a history of nasopharyngeal carcinoma (T2N2M0) treated with radiotherapy in 1995. There was non-pitting oedema of the right upper lid. Liver and renal function tests were normal. She had no oedema in her extremities or elsewhere.

Computed tomography of the orbits showed smooth soft tissue oedema of the right upper lid with no abnormal mass. Cavernous sinuses were normal. Patchy sclerosis in the skull base was present and thought to represent post-radiotherapy changes.

Right upper lid blepharoplasty had been performed elsewhere in March 2009, where excessive and thickened skin was excised together with hypertrophic orbicularis muscles. The orbital septum was kept intact with preservation of the preaponeurotic fat pad. A similar repeat procedure was performed 4 months later by the same surgeon for persistent symptoms.

In 2019, the patient presented to us with residual bilateral upper lid oedema. Palpebral fissure height was 5 mm on the right eye and 6 mm on the left. Marginal reflex distance was 0 mm on the right eye and 1 mm on the left. Levator function was 9 mm on both eyes. There was secondary mechanical partial ptosis, loss of lid crease, and facial lymphoedema.

Surgical correction of eyelid lymphoedema was performed. Histological examination was compatible with lymphoedema. The patient recovered well postoperatively and there was no recurrence 6 months after surgery.

There are only a few reports of eyelid lymphoedema following neck dissection, surgery or radiation.1 2 3 As none of our cases underwent neck dissection, we hypothesise that radiotherapy alone can impede lymphatic drainage with consequent periocular lymphoedema. In this series, eyelid lymphoedema was frequently related to nasopharyngeal carcinoma, unlike other series.

Eyelid lymphoedema presents as a non-pitting oedema with thickening of the eyelid. In cases with severe swelling, visual field defect and disfigurement may occur.

Rosacea is the most reported eyelid lymphoedema association, albeit rare. More common presentations are blepharitis, conjunctivitis, and meibomianitis.3 4 5 6 7

Lymphoedema can usually be managed conservatively with manual drainage, compression garments, and skin care.8 Medical therapy with tetracycline and steroids have limited efficacy.4 5 7 Surgical treatment by debulking and split thickness skin grafting has been reported with favourable results.3 4 9 Lymphovenous anastomosis or bypass is also performed to divert lymphatic drainage to venous circulation.10 Nonetheless this is difficult in the periocular region where a lack of large superficial veins may result in an unsightly facial scar. Therefore, surgical debulking may remain the treatment of choice.

For surgical debulking, excessive skin and orbicularis should be addressed. Orbital septum debulking is essential since fluid tends to accumulate in this loose connective tissue. Debulking of the preaponeurotic fat pad can reduce upper lid swelling and enhance formation of skin crease. In our fourth case without such debulking, there was residual swelling. We addressed this in her last surgery resulting in marked improvement. In all four cases, there was no recurrence as the loose connective tissue was removed with orbital septum and preaponeurotic fat pad debulking. Levator resection should be performed in cases with long-standing oedema and levator muscle dysfunction. Skin crease forming sutures are placed for symmetry with the opposite eye, noting that Asian patients have thicker skin and orbicularis muscle, affecting skin crease formation and margin reflex distance. We prefer an incision 1 to 2 mm lower than the opposite normal side for better symmetry. Although surgery can improve eyelid oedema, patients should be informed that abnormal-appearing skin will persist. The longevity of improvement may be enhanced with presence of scar tissue making oedematous fluid less likely to accumulate.

Concept or design: All authors.
Acquisition of data: All authors.
Analysis or interpretation of data: All authors.
Drafting of the manuscript: All authors.
Critical revision of the manuscript for important intellectual content: HY Chan, HKL Yuen.

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.

As an editor of the journal, HKL Yuen was not involved in the peer review process. Other authors have disclosed no conflicts of interest.

Case 2 in this study has been previously published in part in: Yuen KLH, Kwok YT. Surgical management of unusual eyelid swelling. iPlastics: official newsletter of the Asia Pacific Society of Ophthalmic Plastic and Reconstructive Surgery: 2016; 2(4): 4-6. Permission from the newsletter editor for publication of the case has been obtained. The authors confirm that there is no intentional or unintentional plagiarism in the present manuscript.

This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

This study was conducted in accordance with the Declaration of Helsinki. All patients were informed of the purpose of the study and their consent was obtained for all treatments, procedures, photography, and publication.

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