Mitochondrial cardiomyopathy usually presents in childhood and is estimated to occur in 20% to 40% of children with mitochondrial disease. However, it is a rare cause of cardiomyopathy in adults. We report a case of heart failure due to hypertrophic cardiomyopathy presenting in a 57-year-old female patient with intestinal pseudo-obstruction and bilateral sensorineural deafness. The constellation of diseased organs led to suspicion of underlying mitochondrial disease, subsequently confirmed by genetic mitochondrial DNA (mtDNA) testing that revealed the m.3243 A>G pathogenic variant in the MT-TL1 gene.

A 57-year-old female was referred for investigation of recent-onset congestive heart failure with cardiomegaly and bilateral pleural effusions on chest X-ray together with an elevated serum N-terminal pro-brain natriuretic peptide level of 241 pg/mL (normal <100 pg/mL). She presented with increasing abdominal distension and dyspnoea for 4 months. She had colonic pseudo-obstruction that did not resolve following repeated decompression and was referred for cardiac assessment with reference to fitness for colectomy under general anaesthesia. Apart from gradual hearing loss over the previous 8 years, she had been previously well. She suffered a miscarriage at age 23 years but subsequently gave birth to two apparently healthy daughters at age 32 and 36 years. Her main complaint over the previous year was constipation. There was no history of diabetes, muscle weakness, or visual problems. The older daughter was reported to have a squint since childhood, suggestive of ophthalmoplegia. There was no family history of any hearing, neurological, gastrointestinal or cardiac problems.

Clinically the patient was in distress and pain due to the grossly dilated abdomen from the colonic pseudo-obstruction (Fig 1). Positron emission tomography–computed tomography scan showed dilated bowel (up to 10 cm in diameter) from the caecum to the anus but no evidence of malignancy. Electrocardiogram showed sinus rhythm with left ventricular hypertrophy by voltage criteria and strain pattern. Echocardiogram showed left ventricular hypertrophy with mildly impaired left ventricular systolic function (ejection fraction 40%), diastolic dysfunction and a circumferential pericardial effusion (Fig 2). Computed tomography coronary angiogram was normal. Magnetic resonance imaging (MRI) heart revealed increased T1 mapping but no late gadolinium enhancement. Screening for amyloidosis was negative. Neurological assessment revealed no evidence of muscle weakness and the creatine kinase level was normal. Computed tomography brain showed dense calcification in bilateral lentiform nuclei and MRI brain was essentially normal.

In view of pending rupture of the dilated colon (up to 10 cm), she underwent subtotal colectomy uneventfully. Histopathology of the resected colon showed no evidence of dysplasia or neoplasia. Blood was sent for mitochondrial disorder testing and showed a m.3243A>G mutation in the MT-TL1 gene, with approximately 10% heteroplasmy. The resected large bowel was micro-dissected for heteroplasmy determination of m.3243A>G by droplet digital polymerase chain reaction. The heteroplasmy levels for smooth muscle, epithelium and connective tissue of the large bowel were 77%, 66% and 46%, respectively.

Mitochondrial DNA disease is a multi-system disorder that affects tissues with high energy demands such as the heart, brain, muscle, and endocrine system. It is caused by mutations in either mtDNA or nuclear DNA genes. Defects in mtDNA can be either point mutations or re-arrangements such as deletions or duplications. The m.3243A>G variant within the MT-TL1 gene (encoding the mitochondrial transfer RNA) is a point mutation and the most common heteroplasmic mtDNA disease genotype. This mutation accounts for approximately 80% of the MELAS phenotype (mitochondrial myopathy, encephalopathy, lactic acidosis, plus stroke-like episodes) that features mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes, and which this patient did not have. Other phenotypic variations associated with the m.3243A>G mutation include maternally inherited diabetes and deafness, ocular (eg, progressive external ophthalmoplegia), gastrointestinal, cardiac, and renal involvement. Most carriers of this mutation are asymptomatic due to mitochondrial heteroplasmy, implying the existence of two or more genomes within the same cell. Usually, the proportion of heteroplasmy needs to exceed a threshold level of 60% to 90% for the organ to be clinically affected. The onset and extent of clinical disease are determined by the mtDNA mutation load and threshold. In m.3243A>G mutation carriers, hypertrophic cardiomyopathy is found in about 18% of patients.1

In a small study of 10 m.3243A>G mutation carriers, the skeletal muscle mutation load appeared to correlate with the measures of early cardiac dysfunction on MRI, namely the torsion-to-endocardial strain ratio and radial thickening.2 Different patterns of cardiac involvement are associated with different mtDNA mutations. Although hypertrophic cardiomyopathy is frequently associated with mt-tRNA (transfer RNA) mutations such as the m.3243A>G mutation, restrictive cardiomyopathy is associated with the m.1555A>G mitochondrial ribosomal ribonucleic acid gene mutation. In children with Kearns-Sayre syndrome due to single, large-scale deletions in mtDNA, complete heart block is common.3 In our case, the heteroplasmy level within the different structures in the large bowel (46%-77%) was uniformly higher than in the blood (10%). This was consistent with the clinical presentation of pseudo-obstruction with the large bowel being the major organ involved.

Unfortunately, there is no cure for mitochondrial disease. Device therapy in the form of pacemakers and cardioverter-defibrillators may be required for heart block and ventricular arrhythmias associated with mitochondrial cardiomyopathy. Due to the complexity of mitochondrial disease, it is now recommended that affected patients be assessed using a validated semi-quantitative clinical rating scale, the Newcastle Mitochondrial Disease Adult Scale, to evaluate the different systems involved and to monitor response to treatment. Regular cardiovascular screening is recommended with electrocardiogram and echocardiogram performed at least every 2 years.4

Mitochondrial DNA is strictly maternally inherited, with only rare reports of paternal transmission. This may be due to a dilution effect since the sperm contain only 100 copies of mtDNA compared with 100 000 copies in the unfertilised egg and, secondly, there is elimination of sperm mtDNA in normal embryos. The m.3243 A>G mutation is usually transmitted from mother to offspring with rare reported cases of de novo mutation.5 Genetic counselling in mitochondrial disease may be difficult because of heteroplasmy, mitotic segregation, and mitochondrial bottleneck phenomenon. Phenotypic variations associated with m.3243A>G are due to a different percentage of mutation heteroplasmy in affected organs. It is known that an asymptomatic mother with a subclinical heteroplasmy level can give birth to an affected child with a higher heteroplasmy level. This is explained by the mitochondrial bottleneck theory, whereby redistribution of mtDNA to daughter cells during oocyte production and amplification of the redistributed mtDNA during oocyte development occurs. The unequal mitotic segregation of mtDNA during cell division and the reduction/amplification event leads to a random shift of mtDNA mutational load between generations. This is thought to be responsible for the variable levels of mutation heteroplasmy observed in affected offspring from mothers with pathogenic mtDNA mutations.

Mitochondrial cardiomyopathy is a rare cause of heart failure presenting in adulthood. Mitochondrial disease should be suspected when other organs or tissues are involved. Genetic testing is a powerful diagnostic tool. Severity and prognosis of mitochondrial disease depend on the concentration of heteroplasmy in the affected organs. Screening and follow-up cardiac assessment are recommended due to the progressive nature of cardiac involvement and risk of heart failure and arrhythmias as a cause of death in patients with mitochondrial mutation. Mitochondrial mutations are maternally inherited but the unique features of mitochondrial inheritance, namely mitotic segregation and mitochondrial bottleneck phenomenon, make predictions of inheritance a challenge. Genetic counselling should be offered to the families of an affected individual.

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

The authors had contributed to the manuscript, approved the final version for publication, and take responsibility for its accuracy and integrity.

The authors have no conflicts of interest to disclose.

This case report 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. The patient provided informed consent for all procedures.

1. Pankuweit S, Richter A. Mitochondrial disorders with cardiac dysfunction: an under-reported aetiology with phenotypic heterogeneity. Eur Heart J 2015;36:2894-7. Crossref

2. Hollingsworth KG, Gorman GS, Trenell MI, et al. Cardiomyopathy is common in patients with the mitochondrial DNA m.3243A>G mutation and correlates with mutation load. Neuromuscul Disord 2012;22:592-6. Crossref

3. Bates MG, Bourke JP, Giordano C, d’Amati G, Turnbull DM, Taylor RM. Cardiac involvement in mitochondrial DNA disease: clinical spectrum, diagnosis, and management. Eur Heart J 2012;33:3023-3. Crossref

4. Schaefer AM, Phoenix C, Elson JL, McFarland R, Chinnery PF, Turnbull DM. Mitochondrial disease in adults: a scale to monitor progression and treatment. Neurology 2006;66:1932-4. Crossref

5. de Laat P, Janssen MC, Alston CL, Taylor RW, Rodenburg RJ, Smeitink JA. Three families with ‘de novo’ m.3243A>G mutation. BBA Clin 2016;6:19-24. Crossref

A 54-year-old Caucasian man presented with dyspepsia for 5 months with mild loss of weight. Endoscopic examination showed a 2-cm gastric ulcer with raised edges on the lesser curvature of the stomach. Endoscopic ultrasound demonstrated that the lesion involved the submucosa and muscularis propria, measuring 8 mm thick. Biopsy revealed, along with body-type mucosa, spindle cell tissue, 2 mm in diameter. The cells had indistinct cytoplasm with elongated nuclei showing mild enlargement, and variation in size and shape. The initial comprehensive immunohistochemical staining panel (AE1/3, CAM5.2, c-KIT, CD34, DOG1, actin, desmin, STAT6, synaptophysin, HMB45, CD45, and calretinin) gave no positive results while the Ki67 index was 5% to 10%. Computed tomography scan of the abdomen showed a 1.6-cm submucosal mass located at the gastric lesser curvature. There was no abnormal focal metabolic uptake in positron emission tomography scan. No hypermetabolic lymph node was found. The preoperative diagnosis was a submucosal spindle cell tumour.

Laparoscopic wedge resection of the gastric lesion was performed. Gross examination of the resected specimen showed gastric mucosa measuring 4 cm × 3.5 cm with submucosal tissue of 1 cm thick. There was an ulcerated lesion measuring 0.7 cm × 0.6 cm and 1.6 cm in maximal depth.

Microscopically, a dumbbell-shaped nodule was seen under the ulcer and extending through the muscularis propria to form a smooth nodule on the serosal aspect (Fig 1). Further immunohistochemical staining of the tumour cells was negative for cytokeratin (AE1/3, c-KIT, DOG1, CD31, CD34, desmin, actin, S-100, STAT6, ALK, calretinin, and HMB45. Ki-67 index was not high. The cells, however, showed positive staining for transducin- like enhancer protein 1 (TLE-1) upregulation (Fig 2) consistent with a diagnosis of synovial sarcoma and this was confirmed with fluorescence in situ hybridisation, which demonstrated a positive result for SS18 (synovial sarcoma) translocation. Six peritumoural lymph nodes and adjacent omentum showed no metastasis.

The patient recovered from his surgery without complications. He was followed up for 18 months after surgery with no signs of recurrence.

Synovial sarcoma is a soft tissue sarcoma with common presentation in para-articular regions of the extremities although it is not related to synovium. It was first reported in 1893 and accounts for about 10% of all primary malignant soft tissue neoplasms.1 2 About 80% of synovial sarcomas are found in extremities, particularly the knee in the popliteal fossa, although they have also been reported in anatomical locations away from joints, including deep spaces in the head and neck, chest and abdominal wall, and visceral organs.3 4

Three histological subtypes of synovial sarcoma have been described: monophasic, biphasic, and poorly differentiated patterns. Monophasic synovial sarcoma is the most common subtype, in which the mesenchymal spindle cell component predominates. Biphasic synovial sarcoma has both a mesenchymal spindle cell component and an obvious epithelial component, representing 20% to 30% of synovial sarcomas.5 6 Poorly differentiated synovial sarcoma typically shows small round cell morphology and high mitotic activity, representing 15% to 25% of synovial sarcomas.7

Primary gastric synovial sarcomas are extremely rare, with only 31 cases reported in the English literature. Here we report a patient with primary gastric synovial sarcoma and published cases in the literature are reviewed.

Primary gastric synovial sarcoma is very rare, with the majority of malignant mesenchymal tumours in the stomach represented by malignant gastrointestinal stromal tumours (GISTs) and leiomyosarcoma. Synovial sarcoma has been reported to affect other parts of the gastrointestinal tract, including the oesophagus, duodenum, small bowel, ascending colon mesentery, liver, gastrocolic ligament, or omentum. However, the incidence of these tumours is very low, and few case reports are available in the literature. In 2000, Billings et al8 first reported two cases of primary synovial sarcoma in the gastroesophageal junction and stomach. In 2008, Makhlouf et al9 reported a series of 10 gastric synovial sarcomas, with mean age at diagnosis of 52 years. A recent published case was reported by Fuente et al10 in 2019. The most commonly reported clinical presentations of gastric synovial sarcomas are epigastric pain and anaemia.11 A clinical summary of the 36 cases of primary gastric synovial sarcoma, including our case, is shown in the Table.8 9 10 12 13 14 15 16 17 18 19 20 21 22 23

When a gastric spindle cell tumour is encountered, the differential diagnosis mainly focuses on other gastrointestinal mesenchymal tumours, such as GIST, leiomyoma, leiomyosarcoma, schwannoma and fibromatosis. Appropriate immunohistochemical staining is crucial in order to make a diagnosis of synovial sarcoma. Although TLE-1 is positive in the majority of synovial sarcomas, it is not specific for synovial sarcoma, as it can also be positive in other tumours such as endometrial stromal sarcoma, schwannoma, epithelioid sarcoma, solitary fibrous tumour, and rarely GISTs.

To confirm the diagnosis of synovial sarcoma, molecular analysis is essential. As many as 90% of synovial sarcomas possess a fusion between the SS18 gene on chromosome 18 and an SSX gene found on the X chromosome.11 This translocation, t(X;18), can be reliably detected on formalin-fixed paraffin-embedded tissue by polymerase chain reaction or fluorescence in situ hybridisation.24 25

Optimal treatment for gastric synovial sarcoma is surgical resection. There is no evidence that lymph node dissection (as in gastric adenocarcinoma) will benefit. Our patient underwent laparoscopic wedge resection of the gastric tumour and had an uneventful recovery. After surgery, we did not administer chemotherapy or radiotherapy as the resection margins were clear.

From the literature, all recurrences or disease-related deaths in gastric synovial sarcomas occurred in tumours >3 cm or those containing a poorly differentiated component; however, the prognosis of the disease is uncertain owing to the rare occurrence.

It is difficult to make a preoperative diagnosis of gastric synovial sarcoma based on endoscopic appearance only, as biopsies are usually negative. When sufficient tissue is obtained preoperatively, immunohistochemical staining can be applied. A panel of immunohistochemical stains should be utilised if the diagnosis is not apparent. When surgical resection is performed, the resected specimen should be saved for further evaluation.

When approaching a submucosal lesion identified on endoscopy with uncertain histological diagnosis, treatment usually is directed as if the lesion is a GIST, since this is most common. Local excision without lymphadenectomy is adequate, as in the current patient. Immunohistochemical staining and fluorescence in situ hybridisation are useful in differentiating gastric synovial sarcoma from other gastric spindle cell tumours.

The majority of recurrences in soft tissue sarcomas occur within the first 3 years of observation, and recurrence is rare in gastric synovial sarcoma. The assessment of recurrence risk, based on factors such as tumour grade and size, helps in determining a follow-up policy. According to the 2018 European Society for Medical Oncology Clinical Practice Guidelines26 on soft tissue and visceral sarcomas, the following approach is recommended: follow-up of surgically treated intermediate- or high-grade patients every 3 to 4 months in the first 2 to 3 years, then twice a year up to the fifth year, and once a year thereafter; low-grade sarcoma patients may be followed for local relapse every 4 to 6 months, with chest X-rays or computer tomography scan at longer intervals in the first 3 to 5 years, then annually.26 However, gastric synovial sarcomas are so rare that reliable guidelines cannot be recommended.

Gastric synovial sarcoma is extremely rare, and diagnosis requires specific immunohistochemical and molecular analysis. The presence of spindle cells usually reflects common mesenchymal tumour, yet the diagnosis of synovial sarcoma should also be considered when these cells are observed in gastric tumours and there is a discrepancy between the tumour morphology and the immunohistochemical stain results. The prognosis of these tumours is uncertain, given the rarity of the disease.

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. S Law had the concept of the study, S Law and R Collins acquired the necessary data, all authors analysed and interpreted the data, all authors took part in drafting the manuscript as well as critically revised it for intellectual content.

All authors have disclosed no conflicts of interest.

This case report 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. The patient provided informed consent for all procedures.

1. Suurmeijer A, de Bruijn D, Geurts van Kessel A, et al. Synovial sarcoma. In: Fletcher CD, Bridge JA, Hogendoorn P, Mertens F, editors. WHO Classification of Tumours of Soft Tissue and Bone. 4th ed. Lyon: IARC; 2013: 213-5.

2. Weiss SW, Goldblum JR. Malignant soft tissue tumors of uncertain type. In: Weiss SW, Goldblum JR, editors. Enzinger and Weiss’s Soft Tissue Tumors. 4th ed. St Louis, MO: Mosby; 2001: 1483-565.

3. Spillane AJ, A’Hern R, Judson IR, Fisher C, Thomas JM. Synovial sarcoma: a clinicopathologic, staging, and prognostic assessment. J Clin Oncol 2000;18:3794-803. Crossref

4. Alsharief AN, Fageeh M, Alabdulkarim Y. Monophasic synovial sarcoma presenting as a primary ileal mass: a case report and review of the literature. J Med Case Rep 2012;6:83. Crossref

5. Fisher C. Synovial sarcoma. Ann Diagn Pathol 1998;2:401-21. Crossref

6. McNeill J, Nguyen YV. Synovial sarcoma of the abdominal wall. Radiol Case ReP 2015;2:108. Crossref

7. Köse D, Annagür A, Erol C, Uğraş S, Köksal Y. Synovial sarcoma in a premature newborn. Pediatr Int 2014;56:e17- 20. Crossref

8. Billings SD, Meisner LF, Cummings OW, Tejada E. Synovial sarcoma of the upper digestive tract: a report of two cases with demonstration of the X;18 translocation by fluorescence in situ hybridization. Mod Pathol 2000;13:68-76. Crossref

9. Makhlouf HR, Ahrens W, Agarwal B, et al. Synovial sarcoma of the stomach: a clinicopathologic, immunohistochemical, and molecular genetic study of 10 cases. Am J Surg Pathol 2008;32:275-81. Crossref

10. Fuente I, Bruballa R, Corradetti S, Cavadas D, Beskow A, Wright F. Gastric synovial sarcoma. J Gastrointest Surg 2019;23:1515-7. Crossref

11. Crew AJ, Clark J, Fisher C, et al. Fusion of SYT to two genes, SSX1 and SSX2, encoding proteins with homology to the Kruppel-associated box in human synovial sarcoma. EMBO J 1995;14:2333-40. Crossref

12. Akhunji S, Musil I, Baisre A, Bhattacharyya A, Cranmer L. Synovial sarcoma arising in the gastric wall: case report and literature review. Cancer Ther 2007;5.

13. Wang CC, Wu MC, Lin MT, Lee JC. Primary gastric synovial sarcoma. J Formos Med Assoc 2012;111:516-20. Crossref

14. Sinniah RP, Roche E, Cameron D. GI synovial sarcomas. Clin Transl Gastroenterol 2012;3:e11. Crossref

15. Sahara S, Otsuki Y, Egawa Y, et al. Primary synovial sarcoma of the stomach—a case report and review of the literature. Pathol Res Pract 2013;209:745-50. Crossref

16. Kamata K, Wada R, Yajima N, Sawada M, Wakasa H, Yagihashi S. Primary gastric synovial sarcoma: molecular diagnosis and prediction of prognosis. Clin J Gastroenterol 2013;6:303-8. Crossref

17. Torres Rivas HE, Fernández S, Fresno MF. Primary gastric synovial sarcoma. Pathology 2014;46:253-6. Crossref

18. Michot N, Robert PE, De Muret A, Marques F, de Calan L, Benchellal Z. Gastric synovial sarcoma: case report and systematic review of literature. J Gastrointest Cancer 2014;45 Suppl 1:129-31. Crossref

19. Romeo S, Rossi S, Acosta Marin M, et al. Primary synovial sarcoma (SS) of the digestive system: a molecular and clinicopathological study of fifteen cases. Clin Sarcoma Res 2015;5:7. Crossref

20.Wong NA, Campbell F, Shepherd NA. Abdominal monophasic synovial sarcoma is a morphological and immunohistochemical mimic of gastrointestinal stromal tumour. Histopathology 2015;66:974-81. Crossref

21. So IT, Cho KB, Lee JY, et al. A primary gastric synovial sarcoma: A case report and literature review. Medicine (Baltimore) 2017;96:e8904. Crossref

22. Hu S, Wong K, Ramesh KH, Vilanueva-Siles E, Panarelli N, In H. Diffuse, aggressive metastatic progression after minimally invasive local resection of primary gastric synovial sarcoma: a case report and systematic review of the literature. J Gastrointest Cancer 2019;50:116-22. Crossref

23. Olsen G, Beal E, Pfeil S, Dillhoff M. Primary gastric synovial sarcoma mimicking a gastrointestinal stromal tumour (GIST): gastric synovial sarcoma. J Gastrointest Surg 2018;22:1450-1. Crossref

24. Tsuji S, Hisaoka M, Morimitsu Y, et al. Detection of SYT-SSX fusion transcripts in synovial sarcoma by reverse transcription-polymerase chain reaction using archival paraffin-embedded tissues. Am J Pathol 1998;153:1807-12. Crossref

25. Terry J, Barry TS, Horsman DE, et al. Fluorescence in situ hybridization for the detection of t(X;18) (p11.2;q11.2) in a synovial sarcoma tissue microarray using a breakapart-style probe. Diagn Mol Pathol 2005;14:77-82. Crossref

26. Casali PG, Abecassis N, Aro HT, et al. Soft tissue and visceral sarcomas: ESMO-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2018;29(Suppl 4);iv268-9.

In April 2017, an 81-year-old man presented to the emergency department with acute urinary retention. Digital rectal examination revealed a grossly enlarged prostate with a hard nodule felt at the left lobe. The patient was subsequently catheterised and haematuria with a small number of blood clots was noted. Urine cytology and microbiology were negative. Prostate-specific antigen (PSA) was elevated at 23.8 ng/mL.

Cystoscopy revealed a trabeculated urinary bladder with multiple small bladder diverticula but no mucosal lesion and a grossly enlarged prostate. The patient was prescribed terazosin and successfully weaned off the Foley catheter. However, the patient required repeat admissions for recurrent acute urinary retention. He was managed with an increased dose of terazosin and intermittent self-catheterisation.

Computed tomography (CT) urogram was performed as part of the haematuria examination and revealed an approximately 10-cm hypodense cystic lesion in the rectovesical space. No preserved fat plane was present between the lesion and seminal vesicles and prostate, or the lesion and rectum. Internal enhancing solid components were seen in the left posterior aspect of the mass (Fig a and b).

On magnetic resonance imaging (MRI), the mass was again noted between the rectum and the prostate. The mass showed predominantly T1-weighted hyperintense signal which could represent proteinaceous or blood product. In T2-weighted sequence, the mass was heterogeneously hyperintense. A solid component previously detected on CT scan demonstrated T1- and T2-weighted intermediate signal intensity, with restricted diffusion and contrast enhancement. (Fig c to g) The differential diagnoses included a seminal vesicle or prostatic tumour, a rectal tumour such as gastrointestinal stromal tumour, or a neuroendocrine tumour.

A CT-guided biopsy was performed for histology. The centre of the mass was first biopsied and yielded old blood products. Cytology revealed necrotic cells and blood cells but no tumour cells.

Because of the high suspicion of underlying malignancy, biopsy was repeated under contrast CT guidance. The solid component on the left side of the cystic mass was biopsied and yielded friable soft tissue. Pathology examination revealed tumour cells that comprised closely packed, back-to-back and cribriform glands, lined with a single layer of neoplastic cells with amphophilic cytoplasm, enlarged, roundish nuclei, fine chromatin, and prominent eosinophilic nuclei. It showed no ductal component. Immunohistochemically, the cells were positively stained with PSA and also showed strong and diffuse expression of NKX3.1 (a prostatic marker) but were negative for synaptophysin (a neuroendocrine marker). The overall features were of acinar-type prostatic adenocarcinoma with a combined Gleason score of 8 (4+4).

Positron emission tomography with 68Ga-PSMA tracer was performed for disease staging. Increased 68Ga-PSMA uptake was present in the left prostate lobe spanning from the apex to the base together with a right prostate apex peripheral zone lesion. Multiple 68Ga-PSMA-avid lesions were seen scattered in the cystic mass, in keeping with carcinoma of the prostate. Mildly 68Ga-PSMA-avid lymph nodes were seen at the retrocaval and bilateral posterior triangles, suspicious of nodal metastases. The patient was treated as disease with nodal metastasis. Luteinising-hormone releasing hormone analogue with androgen blockage was commenced as palliative hormonal therapy. The pretreatment PSA in August 2018 was 30.7 ng/mL but had decreased to 0.3 ng/mL in February 2019. At follow-up examination, the patient was able to void well and terazosin was discontinued.

A giant cystic mass in the male pelvis is not common.1 In this case, an elevated PSA could suggest that the cystic pelvic mass was prostatic in origin.2 Most prostatic cystic lesions are benign and malignant prostatic cysts are very rare.3

Prostatic cysts can be congenital or acquired. Congenital cysts are associated with an abnormality in the paramesonephric (Müllerian) duct or mesonephric (Wolffian) duct. Acquired cysts are usually benign and may include retention cysts or prostatic abscess.4

Malignant prostatic cysts include papillary cystadenocarcinoma, combined transitional cell/adenocarcinoma, and cystic prostatic carcinoma.4 Prostatic carcinoma presenting as cystic lesions rather than solid lesions is uncommon. Rarely, leiomyoma or liposarcoma in the prostate may have cystic elements.4

A literature search on cystic prostatic carcinoma and cyst associated with carcinoma of prostate revealed nine case reports with histologically proven cystic prostatic carcinoma between 1991 and 2016 (Table 1).2 5 6 7 8 9 10 11 12 Case reports without full text available and those written in languages other than English were not reviewed.

The clinical findings of our case were similar to those of the other nine reported cases. Cystic prostatic carcinoma usually affects older adults. Patients usually present with mass effect of the prostatic cystic tumour. The size of prostatic cystic tumour is usually large, on average 6.8 cm in this case series (Table 1). The most common presenting symptoms were lower urinary tract symptoms and acute urinary retention. In this case series, PSA was often very high, on average 243.2 ng/mL (Table 2).

Clinicians and radiologists should be aware of this disease entity as a differential diagnosis of large cystic mass in the male pelvis. Cystic prostatic carcinoma has been reported with typical imaging features. Imaging findings in our case were consistent with those of other reported cases. On ultrasound or CT examinations, cystic prostatic carcinoma occurs as a large, predominantly cystic mass with wall nodularity. Pathologically, the solid components represent the tumour.5

In keeping with other reported MRI findings, the heterogeneous signal intensity of the cystic components and the presence of soft tissue components in our case were suggestive of a neoplastic cause of prostatic cyst. Similar to usual solid prostatic carcinoma, the solid components of the prostatic cystic tumour in our case were noted with restricted diffusion.

In cystic lesions of the prostate, the presence of blood from aspiration should raise suspicion of malignancy, either the cystic mass is malignant or there is associated prostate carcinoma.9 These aspirates were reported to contain a high concentration of PSA and γ-seminoprotein.12 To obtain histology and confirm the diagnosis, biopsies should be performed on the solid components of the prostatic cystic tumour to maximise the yield.

In our case and nine reviewed case reports, all pathological findings of cystic prostatic carcinoma were adenocarcinoma. Of them, one case was reported to have a ductal component. However, the pathogenesis of cystic prostatic carcinoma is not well understood. It has been hypothesised that it is either associated with a pseudocyst due to central necrosis or haemorrhage in the prostatic carcinoma or with malignant degeneration of a retention cyst.9 A Japanese study of prostate cancer with cyst formation found that most reported cystic prostatic carcinomas were pseudocysts with haemorrhage; only 17% were derived from degeneration of a retention cyst.13

Tumour staging affects treatment. Among the nine cases reviewed, bone scan was often performed to detect bone metastases. The treatment strategy for cystic prostatic carcinoma includes curative and palliative treatment. The modalities of treatment in this case series were similar to those for classic prostatic carcinoma and included surgery, radiotherapy, and hormonal therapy.

Among the nine cases reviewed, most patients were followed up with PSA level after treatment and a reduced PSA level was noted in all cases. Some cases also had imaging follow-up of the tumour and showed size reduction. Unfortunately, most case reports had no long-term follow-up results available.

In conclusion, malignant prostatic cysts are rare but an important differential diagnosis in prostatic cystic lesion. Prostatic cystic lesion with nodular wall and internal solid components is highly suspicious of cystic prostatic carcinoma. The MRI features of cystic prostatic carcinoma include evidence of haemorrhage, heterogeneous signal intensity of the cystic component, and presence of soft tissue elements. Image-guided biopsy targeting the solid component is suggested to obtain a histological diagnosis.

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: KH Fung, WK Tsang, PCH Kwok.
Acquisition of data: KH Fung, WK Tsang, PCH Kwok, WT Lee.
Analysis or interpretation of data: KH Fung, WK Tsang, WT Lee.
Drafting of the article: KH Fung, WK Tsang, WT Lee.
Critical revision for important intellectual content: All authors.

The authors have no conflicts of interest to disclose.

This case report 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. The patient provided informed consent for all procedures.

1. Lim DJ, Hayden RT, Murad T, Nemcek AA Jr, Dalton DP. Multilocular prostatic cystadenoma presenting as a large complex pelvic cystic mass. J Urol 1993;149:856-9. Crossref

2. Tsuji H, Hashimoto K, Katoh Y, Iguchi M. Prostatic cancer with huge cystic degeneration. Urol Int 1999;62:48-50. Crossref

3. Hamper UM, Epstein JI, Sheth S, Walsh PC, Sanders RC. Cystic lesions of the prostate gland. A sonographic-pathologic correlation. J Ultrasound Med 1990;9:395-402. Crossref

4. Curran S, Akin O, Agildere AM, Zhang J, Hricak H, Rademaker J. Endorectal MRI of prostatic and periprostatic cystic lesions and their mimics. AJR Am J Roentgenol 2007;188:1373-9. Crossref

5. Llewellyn CH, Holthaus LH. Cystic carcinoma of the prostate: findings on transrectal sonography. AJR Am J Roentgenol 1991;157:785-6. Crossref

6. Parr NJ, Hawkyard SJ. Carcinoma of the prostate presenting as cystic pelvic mass. Br J Urol 1994;73:213-4. Crossref

7. Agha AH, Bane BL, Culkin DJ. Cystic carcinoma of the prostate. J Ultrasound Med 1996;15:75-7. Crossref

8. Khorsandi M. Cystic prostatic carcinoma. J Urol 2002;168:2542. Crossref

9. Chang YH, Chuang CK, Ng KF, Liao SK. Coexistence of a hemorrhagic cyst and carcinoma in the prostate gland. Chang Gung Med J 2005;28:264-7.

10. Chen CH, Lin YH, Tzai TS, Tsai YS. Prostate cancer associated with hemorrhagic cyst: findings on transrectal Doppler sonography. J Med Ultrasound 2008;16:292-5. Crossref

11. Ng KL, Sathiyananthan JR, Dublin N, Razack AH, Lee G. Cystic adenocarcinoma of prostate: a case report. J Health Transl Med 2011;14:21-2. Crossref

12. Nerli RB, Patil R, Sharma V, Ghagane SC, Hiremath MB. Cystic prostatic carcinoma. Clin Oncol 2016;1:1154.

13. Kim SC, Fujimoto K, Matsumoto Y, et al. A case of prostate cancer with cyst formation [in Japanese]. Hinyokika Kiyo 2001;47:653-6.

An 81-year-old woman was admitted in June 2014 to Tseung Kwan O Hospital with aspiration pneumonia. She had temporal lobe necrosis and absence seizure after radiotherapy for nasopharyngeal carcinoma. She was prescribed lifelong oral phenytoin with no adverse reaction reported to date. Oral phenytoin was changed to intravenous, 100 mg every 8 hours, via a 22G catheter in her right wrist due to oropharyngeal dysphagia. The catheter had been changed several times due to blockage with no apparent extravasation. Erythematous swelling of the skin around previous cannula sites was treated as cellulitis by intravenous ciprofloxacin.

The following day the patient’s right hand deteriorated and showed marked circumferential purplish discolouration, swelling, and gangrenous changes to the skin (Fig 1). Similar minor changes over the left hand were noted. She was afebrile and not septic. White cell count (12.8 × 10⁹/L) was mildly elevated and C-reactive protein was elevated at 196 mg/L. Nonetheless, these results could be interpreted as being due to concurrent aspiration pneumonia.

Computed tomographic angiography revealed fluid collection in the patient’s right hand up to the right forearm with reasonable arterial supply. Intravenous penicillin G and ciprofloxacin were started. Serial clinical assessments prior to surgery showed no further deterioration. Emergency incision, drainage, and carpal tunnel release were performed. Findings were skin and fat necrosis, venous thrombosis and a large amount of clear fluid over the fascial layers of the palm and fingers. There was no turbid or dishwater discharge. The transverse carpal retinaculum was thickened and tight. Mild necrosis of the right-hand small muscles was noted. Cultures of intra-operative tissue samples were negative for micro-organisms.

On day 15 of intravenous phenytoin injection, the patient was diagnosed with purple glove syndrome (PGS). Intravenous phenytoin was stopped immediately and changed to valproate. The condition of the patient’s left-hand improved rapidly but that of her right hand continued to deteriorate (Fig 2) and necessitated below-elbow amputation. The amputation wound healed and she was referred for rehabilitation.

An 87-year-old woman with brain metastasis from lung carcinoma was prescribed oral phenytoin for epilepsy. She was admitted to Tseung Kwan O Hospital in April 2016 with fever. She was prescribed 100 mg phenytoin every 8 hours via a 22G catheter in her left hand due to potential dysphagia. She complained of painful swelling of her left hand after several doses of phenytoin. There was no extravasation of drug. The patient was afebrile and not septic. Diffuse circumferential purplish, tender swelling of the distal left forearm and left hand was noted. The patient’s hand was in intrinsic minus posture. There was no crepitation or fluctuance. The patient’s left wrist and finger movements were limited by pain. Passive stretching of the fingers exacerbated her pain. Radial pulse was palpable with good capillary refill. White cell count (12.4 × 10⁹/L) and C-reactive protein were slightly elevated (17.2 mg/L).

The patient was suspected to have PGS of her left hand complicated by compartment syndrome. Intravenous phenytoin was stopped 1 day after injection and switched to valproate. Serial clinical assessments prior to surgery revealed no further deterioration. Emergency fasciotomy and carpal tunnel release were performed. Intra-operative findings were consistent with compartment syndrome and PGS. There was no evidence of necrotising fasciitis. Cultures of intra-operative tissue samples were negative for micro-organisms. Debridement and primary wound closure were performed 12 days after fasciotomy and the patient was transferred for rehabilitation.

Subsequently, the patient developed a breakthrough seizure and was prescribed intravenous phenytoin via her right hand because the physician did not notice that the patient had previously developed PGS as a complication of this treatment. She developed PGS of her right hand complicated by compartment syndrome. Emergency fasciotomy and carpal tunnel release of the right forearm and right hand were performed. Debridement and primary closure of wounds were performed 16 days after fasciotomy. In order to avoid future complications, a note was made in her medical records that she had an adverse reaction to phenytoin.

Purple glove syndrome is an adverse reaction to intravenous phenytoin. Its incidence has been reported to range from 1.5% to 5.9%.1 Its manifestation includes pain, skin discolouration, blister formation, sloughing, ulceration, necrosis, and compartment syndrome at the injection site within hours of drug administration. Differential diagnoses include extravasation of the medication, cellulitis, peripheral vascular disease, venous thrombosis, and collagen vascular disease.2

The pathogenesis of PGS is poorly understood. It has previously been considered to be a result of extravasation of highly alkaline phenytoin (pH 12).3 4 However, PGS can occur in the apparent absence of extravasation. Histological examination has suggested thrombosis might play a role in pathogenesis.3 To further complicate the matter, PGS has also been reported to be possible following oral phenytoin administration.4 There is no literature to date to correlate any intravenous complication with previous use of oral medication.

Risk factors for PGS after intravenous phenytoin administration include older age, female sex, peripheral vascular disease, sepsis, history of chronic debilitating disease, number of doses, higher dosage (>15-20 mg/kg body weight), higher infusion rate (>25 mg/min), and use of an intravenous catheter <20G.5

Initial management includes analgesia, elevation of the affected limb, compression, massage, and gentle heat. Phenytoin should be stopped and changed to an alternative antiepileptic. Most cases of PGS are mild and can be resolved with no long-term sequelae. Management is mainly supportive. However, PGS may progress to limb ischaemia and compartment syndrome. Frequent monitoring of neurovascular status is required. Vascular study should be performed if perfusion is compromised.5 Anticoagulation, thrombectomy or thrombolysis should be considered when arterial thrombosis is identified. Emergency fasciotomy should be performed for compartment syndrome. An unsalvageable limb should be amputated. Amputation has been reported to be necessary in 10.1% of cases.5 The use of regional blockade and hyaluronidase remains experimental.5

Purple glove syndrome may be prevented by avoiding phenytoin if there is an alternative agent with similar efficacy, for example valproate. Otherwise, oral phenytoin is preferred. If intravenous phenytoin is used, it should be administered via a larger catheter into a larger vein, at the correct dosage and infusion rate, and with a post-infusion saline flush.5

All authors contributed to the concept of study, acquisition and analysis of data, drafting of the article, 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.

The authors have no conflicts of interest to disclose.

This case report 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. The patient provided informed consent for all procedures.

1. Rajabally H, Nageshwaran S, Russell S. An atypical case of purple glove syndrome: an avoidable adverse event. BMJ Case Rep 2012;2012. pii: bcr0120125653. Crossref

2. Lalla R, Malhotra HS, Garg RK, Sahu R. Purple glove syndrome: a dreadful complication of intravenous phenytoin administration. BMJ Case Rep 2012;2012. pii: bcr2012006653. Crossref

3. Okogbaa JI, Onor IO, Arije OA, Harris MB, Lillis RA. Phenytoin-induced purple glove syndrome: a case report and review of the literature. Hosp Pharm 2015;50:391-5. Crossref

4. Bhattacharjee P, Glusac EJ. Early histopathologic changes in purple glove syndrome. J Cutan Pathol 2004;31:513-5. Crossref

5. Garbovsky LA, Drumheller BC, Perrone J. Purple glove syndrome after phenytoin or fosphenytoin administration: review of reported cases and recommendations for prevention. J Med Toxicol 2015;11:445-59. Crossref

A 62-year-old man presented to Queen Elizabeth Hospital in November 2015 with sudden-onset chest pain radiating to his back and left lower limb numbness for 3 hours. He had previously suffered a stroke from which he had made a good recovery and could walked unaided. There was decreased sensation of the entire left lower limb that was cooler than the right. All pulses over the left lower limb were absent but motor power was intact. He did not complain of abdominal pain and his abdomen was neither distended nor tender. He was haemodynamically stable, and auscultation revealed normal heart sounds.

Contrast-enhanced computed tomography (CT) scan revealed a type A dissection from the aortic root down to the left external iliac artery. No haemopericardium or pericardial effusion was noted. Celiac artery and superior mesenteric artery (SMA) originated from both a true and false lumen. The origin and proximal segment of the SMA and celiac artery were compressed by the thrombosed false lumen (Fig 1). Bowel wall was well enhanced. There was cranial extension of the dissection into the right common and internal carotid arteries. The cerebral arteries were still opacified. Computed tomography brain showed early ischaemic change in the right cerebellar hemisphere.

Arterial blood gas analysis and serum lactate level were normal. Transthoracic echocardiography detected an intimal flap at the aortic root. Mild aortic regurgitation was present. Left ventricular function was good.

The patient had a type A aortic dissection with left lower limb acute ischaemia. Emergency interpositional ascending aortic grafting was performed to close the entry site of the ascending aorta dissection and to re-expand the true lumen. Postoperatively, the patient was haemodynamically stable and all left lower limb pulses reappeared.

A new CT scan of the abdomen revealed improved perfusion to the celiac artery. Nonetheless, the SMA remained severely stenotic with only a thin line of contrast enhancement evident in the true lumen. Enhancement of the jejunal wall was decreased. The SMA had both restricted inflow at the orifice and outflow due to compression by the thrombosed false lumen.

Emergency endovascular stenting and open fenestration of the SMA was performed in the hybrid operation theatre. A 5-French arterial sheath was inserted into the right common femoral artery. The true lumen orifice of the SMA was cannulated with a 5-French Yashiro Glidecath catheter (Terumo, Japan) and a 0.035-inch hydrophilic guidewire (Terumo, Japan). The 0.035-inch hydrophilic guidewire (Terumo, Japan) was exchanged for a Rosen guidewire (Cordis, US). The 5-French arterial sheath was exchanged for an 8-French Arrow-Flex guiding sheath (Arrow International, US). A 10-mm × 12-mm Genesis balloon expandable stent (Cordis, US) was deployed at the SMA orifice. Arteriogram showed improvement of flow at the SMA orifice only (Fig 2). Laparotomy was performed. The small and large bowel were not infarcted but lacked peristalsis. The SMA distal to the middle colic artery was bluish in appearance due to thrombosis. Longitudinal arteriotomy was made. All the thrombus in the false lumen was removed. Longitudinal fenestration was made at the dissection flap. The true lumen circulation was re-established with thrombectomy using a 3-French Fogarty catheter. The arteriotomy was closed with a saphenous vein patch. The small bowel appeared healthy after revascularisation. On-table duplex ultrasonography revealed good flow along the SMA.

The patient was transferred to the intensive care unit and extubated 4 days after surgery. He had no neurological deficits or abdominal symptoms. All distal pulses were normal. He recovered well and was discharged from hospital on aspirin 42 days after admission.

Serial follow-up CT scans after the operation showed a patent SMA and celiac artery. The patient remained asymptomatic at a follow-up examination 2 years later.

Acute dissection is one of the most lethal surgical emergencies of the aorta. It results from a tear in the aortic wall intima that extends into the media to create a false lumen and a dissection flap. It is categorised according to the Stanford classification. Visceral malperfusion occurs in 16% to 33% of cases1 due to anterograde propagation of the dissection from the ascending aorta to the level of the aortic visceral branches. This leads to mesenteric ischaemia, organ dysfunction, and systemic metabolic abnormalities. Although the results of surgical treatment for acute type A aortic dissection have improved due to technical advances, mortality remains as high as 89% in the presence of visceral ischaemia.2 It has been suggested that unless pericardial tamponade is present, restoration of visceral perfusion by endovascular techniques should take precedence, especially in cases with a high degree of mesenteric ischaemia and metabolic disturbance.3 This can improve metabolic status and reduce the intra-operative risk of subsequent dissection repair. However, the extent of intestinal malperfusion is difficult to assess since clinical signs typically present late: 75% of patients have no clinical evidence at presentation, as in our patient. This can delay diagnosis and management contributing to the high mortality. The use of biomarkers such as serum lactate has been suggested as potentially useful indicators of mesenteric ischaemia.4 5 If the initial lactate level is high with no other cause and radiological or clinical evidence of bowel ischaemia is present, revascularisation using percutaneous endovascular techniques should be performed first to alleviate intestinal ischaemia, followed by serial measurements of lactate level to look for improvement in peripheral perfusion.3 If the lactate level is persistently high, surgical revascularisation must be considered.

Our patient had no clinical or biochemical signs suggestive of bowel ischaemia. Therefore, interpositional ascending aortic grafting was performed first, since proximal extension of the dissection would be dangerous and entry site closure may improve blood flow along the SMA. The left lower limb pulses reappeared after surgery. However, CT did not show similar improvement in the SMA; on the contrary, the jejunum showed decreased enhancement. Superior mesenteric artery revascularisation was indicated. An anterograde approach was adopted for endovascular stenting of the SMA orifice, followed by open fenestration and closure with vein patch distally. No bowel resection was required. The successful outcome in this patient demonstrates good treatment prioritisation, prompt decision making, and multidisciplinary cooperation in the management of type A aortic dissection with peripheral malperfusion.

The authors have made substantial contributions to the concept or design of this study, acquisition of data, analysis or interpretation of data, drafting of the article, and critical revision for important intellectual content. The authors had full access to the data, contributed to the study, approved the final version for publication, and takes responsibility for its accuracy and integrity.

The authors have disclosed no conflicts of interest.

This research 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. The patient provided informed consent for all procedures.

1. Okita Y, Takamoto S, Ando M, Morota T, Kawashima Y. Surgical strategies in managing organ malperfusion as a complication of aortic dissection. Eur J Cardiothorac Surg 1995;9:242-6. Crossref

2. Girardi LN, Krieger KH, Lee LY, Mack CA, Tortolani AJ, Isom OW. Management strategies for type A dissection complicated by peripheral vascular malperfusion. Ann Thorac Surg 2004;77:1309-14. Crossref

3. Slonim SM, Nyman U, Semba CP, Miller DC, Mitchell RS, Dake MD. Aortic dissection: percutaneous management of ischemic complications with endovascular stents and balloon fenestration. J Vasc Surg 1996;23:241-51. Crossref

4. Muraki S, Fukada J, Morishita K, Kawaharada N, Abe T. Acute type A aortic dissection with intestinal ischemia predicted by serum lactate elevation. Ann Thorac Cardiovasc Surg 2003;9:79-80.

5. Murray MJ, Gonze MD, Nowak LR, Cobb CF. Serum D(-)-lactate levels as an aid to diagnosing acute intestinal ischemia. Am J Surg 1994;167:575-8. Crossref