Postmenopausal hyperandrogenism due to an ovarian sex cord-stromal tumour causing elevated dehydroepiandrosterone sulphate: a case report.

BACKGROUND: The source of excess androgen can be obscure in postmenopausal women with new-onset hyperandrogenism. If serum dehydroepiandrosterone sulphate (DHEAS) is raised, it is presumed to be of adrenal origin because DHEAS is exclusively produced from adrenal cortical cells. This reports an elderly female presenting with new-onset hyperandrogenism due to an ovarian sex cord-stromal tumour, associated with increased serum DHEAS levels. CASE DESCRIPTION: A 76-year-old female with long-standing diabetes and hypertension presented with hirsutism and male type alopecia for six months. She had menopause at 55 years of age. There was a pelvic mass on examination. Total testosterone was 6.106 ng/ml (0.124-0.357) and DHEAS was > 1000 µg/dL (35-430). Contrast-enhanced computed tomography of the abdomen and pelvis showed a heterogeneously enhancing complex mass measuring 11 × 8 cm in the left adnexal region. Adrenal glands were normal. She underwent total abdominal hysterectomy, bilateral salphingo-oophorectomy, and omentectomy. Both testosterone and DHEAS normalised following surgery. Histology revealed a sex cord-stromal tumour, likely a steroid cell tumour with malignant potential. Fluorodeoxyglucose-Positron emission tomography did not show any additional lesions. CONCLUSIONS: Due to the lack of sulfotransferase in ovarian tissue, markedly elevated DHEAS originating from an ovarian neoplasm is unusual. This phenomenon has not been described except in a patient with a steroid cell tumour causing Cushing syndrome and hyperandrogenism. The mechanism of this rare occurrence remains elusive. Knowledge of this unusual presentation would enable the clinicians to be cautious in localising the androgen source in women with hyperandrogenism.

Bladder cancer in women: a Sri Lankan study

Introduction: Bladder cancer (BC) is the ninth commonest cancer globally, and ranks 19th among women. The literature on BC in women is sparse, and the knowledge on the variations of tumour characteristics in South Asian female BC is limited. The objective of this study was to describe the clinicopathological characteristics of BC in women and compare them with male BC. Methods: A retrospective analysis of all female patients with histopathologically proven newly diagnosed primary BC from January 2007 to January 2017 was done at the Urology Unit, National Hospital of Sri Lanka, and the findings were compared with men with BC during the same period. Results: There were 314 patients with primary BC, of which 55(17.5%) were women, with a male:female ratio of 4.7:1. Only 70.9% of women had haematuria at presentation. Forty-four women (80%) had urothelial bladder cancers(UBC). The mean age of women with UBC was 67±SD13.2 years, and for non-urothelial bladder cancers(NUBC) was 62.5±SD 12.7 years. NUBC in women accounted for a disproportionately higher percentage in comparison to men (20% vs.5.4%, p<0.001). Of the UBCs, muscle invasive BC accounted for 45.5% (20/44) in women as opposed to 33.5% (82/245) in men. Women had a significantly higher proportion of solid tumours (40%vs.22.8%,p=0.008) compared to men. Conclusion: Primary BC in women has a significantly higher proportion of NUBC and muscle invasive UBC, which are more aggressive cancers, compared to men. Furthermore, the lack of haematuria in >25%, and higher incidental diagnosis, with inherently thinner bladder wall, makes primary BC in women more likely to present late, in a more advanced state.

Embolizing pulmonary aspergillosis, mycobacterial & aspergillous splenic abscess and cytomegalovirus co-infection following steroid induced immunosuppression: a case report.

BACKGROUND: Aspergillosis is a serious infection particularly affecting the immunodeficient host. Its co-infection with tuberculosis and cytomegalovirus has not been reported before. Embolic events are well recognized with aspergillous endocarditis and aortitis. Splenic abscess is a rare serious complication of disseminated aspergillosis and is difficult to treat. We report the first case of multiple embolic events and splenic abscess in a patient with pulmonary aspergillosis and cytomegaloviral and tuberculous co-infection, without endocarditis or aortitis. CASE PRESENTATION: Thirty-year-old male presented with fever and non-productive cough while on glucocorticoids for glomerulonephritis. He was found to have pulmonary aspergillosis and subsequently developed bilateral lower limb and cerebral fungal emboli and fungal abscess in the spleen. He had IgM and B cell deficiency and cytomegalovirus (CMV) and tuberculous co-infections. He recovered after prolonged course of antimicrobials, splenectomy and cessation of glucocorticoid therapy which also lead to the resolution of immune deficiencies. CONCLUSION: This report illustrates rare combination of B and T cell suppressive effects of glucocorticoids leading to co-infections with CMV, Mycobacterium tuberculosis and Aspergillus and systemic fungal embolization from pulmonary aspergillosis.

Star fruit nephrotoxicity: a case series and literature review.

BACKGROUND: Star fruit is a popular medicinal fruit in the tropics. Its hypoglycaemic properties are considered useful in achieving glycaemic control in diabetes. Star fruit induced nephrotoxicity is a rare cause of acute kidney injury in individuals with both normal and reduced baseline renal function. We present three cases of acute kidney injury due to star fruit nephrotoxicity from Sri Lanka, and discuss the published literature on this topic. CASE PRESENTATION: Three Sri Lankan patients, all with a background of diabetes, presented to us with acute nausea and anorexia following recent consumption of star fruit. Two patients complained of diarrhoea and one patient complained of intractable hiccoughs. They all had elevated serum creatinine on admission. Two were known to have normal baseline serum creatinine levels. On renal biopsy two had evidence of oxalate crystal deposition. One did not show crystal deposition but had acute interstitial nephritis for which no alternate cause could be identified. Two were treated with short courses of prednisolone and two required acute haemodialysis. All recovered renal function, with both patients with known baselines approaching their premorbid serum creatinine levels. CONCLUSION: Consumption of star fruit, especially on an empty stomach or in a state of dehydration may precipitate acute kidney injury. A history of star fruit ingestion must be actively looked for in patients presenting with unexplained acute kidney injury. The use of star fruit as a therapy for diabetes should be discouraged.

In situ immunopathological changes in cutaneous leishmaniasis due to Leishmania donovani.

Cutaneous leishmaniasis in Sri Lanka is a newly established parasitic disease caused by the usually visceralizing Leishmania donovani. Skin lesions manifest as non-itchy, non-tender papules, nodules or ulcers. In situ cytokine expression provides clues for immunopathogenesis of this localized form of disease. Skin biopsies from 58 patients were analyzed for histological appearance and in situ cytokine expression of T-helper 1 (Th1) and T-helper 2 (Th2) cytokines, namely interferon (IFN)-γ, interleukin (IL)-12A, tumor necrosis factor (TNF)-α, IL-4 and IL-10 by real-time RT-PCR. Significant up-regulation of the Th1 cytokine IFN-γ and down-regulation of the Th2 cytokine IL-4 were seen in patients compared to healthy controls. Significantly elevated tissue expression of IFN-γ and TNF-α was seen in lesions that presented later than 6 months from the time of onset, while IL-4 expression was more prominent in lesions that responded poorly to antimony therapy. A prominent Th1 response appears to support resolving of lesions, whereas a Th2-biased milieu tends to favor poor responsiveness to antimony and delayed lesion healing in L. donovani infections in Sri Lanka.

Incidence of prostate cancer in Sri Lanka using cancer registry data and comparisons with the incidence in South Asian men in England.

OBJECTIVE: •To investigate the incidence of carcinoma of the prostate (CaP) in Sri Lanka and compare the rates with the migrant population in the UK. METHODS: •The Sri Lanka cancer registry data were used to determine the rates of CaP in Sri Lanka from 2001 to 2005. •The incidence of CaP in 8,426,000 men, aged ≥30 years, was analysed using 5-year age bands and age-standardized rates were calculated using European standard population data. •The relative risk was calculated by comparison with the South Asian migrant population in the UK using the Prostate Cancer in Ethnic Subgroups (PROCESS) study data, a population-based retrospective cohort study of 2140 men carried out over a 5-year period in four predefined areas of southern England. •Data from incidental findings of CaP in Sri Lanka on transurethral resection of the prostate (TURP) specimens were also analysed. RESULTS: •In all, 1378 new cases of CaP were diagnosed during the 5-year period with a mean age of 69.2 years at diagnosis. •Compared with the previous 5 years, the incidence of CaP had doubled to 5.7 per 100,000, but was significantly lower than in the PROCESS study (relative risk 0.25). •Districts with a higher population density had higher adjusted rates of CaP in Sri Lanka (5.8-12.4 per 100,000). •For TURP specimens, 16.8-18.75% had incidental diagnoses of CaP in Sri Lanka, higher than other published studies. CONCLUSIONS: •The Sri Lankan cancer registry data showed a low rate of CaP, similar to other South Asian countries, but the actual incidence of CaP in Sri Lanka is probably higher than reported, as seen in the densely populated districts and the high rate of incidental diagnosis of CaP in TURP specimens. •The incidence of CaP in migrant South Asians in the UK was much higher than in Sri Lanka. •Further studies are required to examine the environmental and genetic components which may be responsible for the low incidence of CaP in Sri Lanka.

Pulmonary langerhans cell histiocytosis masquerading as tuberculosis in an infant.

A 4-month-old infant presented with continued fever, unresolving bronchopneumonia and household contact with sputum-smear-positive tuberculosis (TB) and showed marginal improvement on anti-TB chemotherapy. Recurrent pneumothorax prompted the clinical diagnosis of TB to be revised. High-resolution CT scan of the chest and open lung biopsy confirmed the diagnosis of pulmonary Langerhans cell histiocytosis. Treatment with prednisolone and vinblastin resulted in settling of fever and resolution of respiratory symptoms and signs. In communities where the prevalence of TB is high, unusual presentations should prompt consideration of alternative diagnoses.

Variations in the Density and Distribution of Cajal Like Cells Associated With the Pathogenesis of Ureteropelvic Junction Obstruction: A Systematic Review and Meta-Analysis.

Introduction: Cajal like cells (CLCs) in the upper urinary tract have an ability to generate coordinated spontaneous action potentials and are hypothesized to help propel urine from renal pelvis into the ureter. The objective of this review was to describe the variations in the density and distribution of CLCs associated with ureteropelvic junction obstruction (UPJO). Materials and Methods: Studies comparing the density and distribution of CLCs in the human upper urinary tract in patients with UPJO and healthy controls were included in this systematic review. We searched online electronic databases; Ovid MEDLINE, Scopus, PubMed and Cochrane reviews for the studies published before October 31, 2020. A meta-analysis was conducted to compare the density of CLCs at the ureteropelvic junction (UPJ) in patients with UPJO and matched controls. Results: We included 20 and seven studies in the qualitative and quantitative synthesis, respectively. In majority (55%) CLCs were located between the muscle layers of the upper urinary tract. The CLC density in the UPJ gradually increased with aging in both healthy subjects and patients with UPJO. The pooled analysis revealed that the density of CLCs at the UPJ was significantly low in patients with UPJO compared to the controls (SMD = -3.00, 95% CI = -3.89 to -2.11, p < 0.01). Conclusions: The reduction in CLC density at the UPJ in patients with UPJO suggests a contribution from CLCs in the pathogenesis of UPJO. Since age positively correlates with CLC density, it is imperative to carefully match age when conducting case control studies comparing the CLC density and distribution. Protocol Registration Number: CRD42020219882.

A closer look at NIFTP.

Despite the rise in the incidence of papillary thyroid carcinoma (PTC) during the last 30 years, the mortality rate due to PTC has remained static. One reason for this phenomenon is the indolent nature of some of the tumors that are diagnosed as PTC. A subgroup of tumors, which often exhibited such indolent behavior, was encapsulated/well-circumscribed follicular lesions that showed PTC nuclear features. Despite their indolent behavior, these tumors were managed as was any other PTC, often with total thyroidectomy and radioactive iodine (RAI) treatment. In order to prevent overtreatment of these tumors, they were recently reclassified as "non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)." Since it is proposed that NIFTP be managed in a more conservative manner, its diagnosis is now based on strict histological criteria. The genetic basis of these diagnostic criteria and the utility of molecular markers in the diagnosis of NIFTP are currently being scrutinized. The aim of this review is to discuss the events that led to the emergence of the term NIFTP, as well as its histological and molecular background.

BRAF-Oncogene-Induced Senescence and the Role of Thyroid-Stimulating Hormone Signaling in the Progression of Papillary Thyroid Carcinoma.

Oncogene-induced senescence (OIS) explains the phenomenon of cellular senescence triggered by the action of oncogenes. It is a mechanism adopted by a cell to inhibit progression of benign tumors into malignancy, occurs in premalignant lesions, and is almost never present in malignant lesions. BRAF mutations occur in about 40-45% of all papillary thyroid carcinomas (PTCs) and of which 99.7% is the BRAFV600E mutation. A unique phenotype of the BRAFV600E mutation is the upregulation of the thyroid-stimulating hormone receptor (TSHR) on thyrocyte membranes. Despite the overexpression of the receptor, BRAFV600E cells undergo cell cycle arrest leading to OIS via a negative feedback signaling mechanism. A simultaneous increase in serum thyroid-stimulating hormone (TSH) in response to hypothyroidism (common in autoimmune diseases such as Hashimoto's thyroiditis) would cause senescent tumor cells to overcome OIS and proceed towards malignancy, hence showing the importance of TSH/TSHR signaling in the development of PTCs. Increase in TSH/TSHR signaling triggers an increase in levels of downstream enzymes such as manganese superoxide dismutase (MnSOD) and dual-specific phosphatase 6 (DUSP6) which eventually results in the production of oncogenic proteins such as c-Myc. Therefore, the detection of these genetic alterations as effective biomarkers for premalignant lesions of PTC is important in clinical settings and techniques such as polymerase chain reaction-mediated restriction fragment length polymorphism (PCR-RFLP) and real-time PCR can be used to detect the BRAFV600E point mutation and overexpression of TSHR, MnSOD, and DUSP6, respectively.

Tissue Impression Smears as a Supplementary Diagnostic Method for Histopathology in Cutaneous Leishmaniasis in Sri Lanka.

Cutaneous leishmaniasis (CL) is diagnosed mainly by light microscopy of smears made using lesion material. Histopathology is usually done in atypical presentations or when lesion smears are negative. Tissue impression smears (TIS) made from skin biopsy specimens were compared with histopathology for the diagnosis of CL. Out of the 111 patients included, 83 (74.8%) were positive by either methods. The TIS was positive in 70.3% whereas histopathology was positive in 56.8% of patients. Tissue impression smears can be used as a supplementary diagnostic test that gives sensitive and rapid results when tissue biopsies are used as the source of lesion material for diagnosis of CL.

Lymphangioma of the jejunal mesentery and jejunal polyps presenting as an acute abdomen in a teenager.

Cystic lymphangioma of the small bowel mesentery is a rare clinical entity, especially after childhood. Medical literature reveals a limited number of such cases presenting as acute abdomen due to bowel obstruction, small bowel volvulus and bleeding into the tumour. We present the management experience of an 18-year-old woman who presented with rapid onset diffuse peritonism and raised inflammatory markers. Computed tomography showed a mass in the small bowel mesentery with suspicion of segmental bowel ischaemia. Emergency laparotomy revealed a mass in the mid-jejunal mesentery close to the bowel wall with no bowel ischaemia. The patient made an uncomplicated recovery after segmental bowel resection and end-to-end anastomosis. Histology confirmed the mass as a cystic lymphangioma involving the jejunal mesentery and two small jejunal polyps. Lymphangioma could be considered in the differential diagnosis of an acute abdomen in a young adult when the presentation is atypical.

Primary Signet-Ring Cell Adenocarcinoma of the Urinary Bladder Treated with Partial Cystectomy: A Case Report and Review of the Literature.

Primary signet-ring cell carcinoma is a variant of adenocarcinoma which is extremely rare, associated with poor prognosis and generally found to be resistant to chemotherapy and radiotherapy. We report a case of primary signet-ring cell carcinoma of the bladder which was successfully treated with partial cystectomy. A 71-year-old female with a history of type 2 diabetes, hypertension, and ischaemic heart disease presented with painless haematuria for 2 months' duration. The abdominal ultrasonography showed a localised polypoidal vesical growth arising from the bladder dome. Cystoscopy revealed an exophytic solid tumour in the anterior fundal wall. A deep transurethral resection of bladder tumour was done and histology revealed an adenocarcinoma composed of mucinous and signet-ring cell components. Later, considering the patient's age and the poor general condition, a partial cystectomy was done. Follow-up cystoscopy and ultrasonography were done at 12 months and there was no evidence of tumour recurrence and the patient is currently symptom-free. Partial cystectomy may be considered in patients with localised tumour without evidence of metastasis and poor general condition. Regular cystoscopies and ultrasound imaging are necessary for follow-up and early identification of recurrences.

Low-grade fibromyxoid sarcoma and hyalinizing spindle cell tumor with giant rosettes share a common t(7;16)(q34;p11) translocation.

Low-grade fibromyxoid sarcoma (LGFMS) is a rare metastasizing soft tissue tumor with deceptively bland histologic features. The hyalinizing spindle cell tumor with giant rosettes (HSCT) is thought to be a closely related tumor differing only by the presence of collagen rosettes. We report the occurrence of a common t(7;16)(q34;p11) translocation in 2 cases of HSCT and 2 cases of LGFMS, thereby providing the first cytogenetic proof that LGFMS and HSCT are variants of the same entity. The tumors occurred in the thighs of 2 females and in the buttock and supraclavicular fossa of 2 males. One HSCT had a spectrum of unusual histologic features, including the presence of plump epithelioid cells with abundant cytoplasm and strands and nests of clear epithelioid cells separated by eosinophilic hyalinized stroma. Two cases showed a hitherto unreported, focal staining with epithelial membrane antigen, thus adding to the immunohistochemical profile of these tumors. LGFMS and HSCT probably have a wider spectrum of morphologic features than previously thought, the awareness of which will help pathologists to avoid diagnostic pitfalls. Demonstration of the t(7;16)(q34;p11) translocation will help to diagnose difficult cases with unusual histologic features.

Myositis ossificans and fibroosseous pseudotumor of digits: a clinicopathological review of 64 cases with emphasis on diagnostic pitfalls.

Myositis ossificans (MO) and fibroosseous pseudotumor of digits (FP) are pseudotumoral mimics of malignancy. A review of 50 cases of MO and 14 cases of FP showed that a malignant diagnosis was suggested by referring pathologists in 23% of MO and 9% of FP. The most common misdiagnosis was osteosarcoma. Awareness of the spectrum of clinicopathological features of MO and FP will help pathologists avoid misdiagnoses. A comparison of the clinicopathological features of MO and FP showed that most features were similar, but FP involved an older age group (p<0.001). MO showed a statistically significant higher tendency to contain fibrinous material (p=0.007), edematous lymphangioma-like areas (p=0.013), and cartilage (p=0.017) and FP to contain excessive immature osteoid (p=0.029). These differences may be related to the site of occurrence.

Chondrosarcoma of small bones of the hand.

A clinicopathological review of 23 patients (mean age, 67 years; range, 42-85 years) with chondrosarcoma of the bones of the hand was done. The mean follow up was 8.5 years. Eleven patients presented with a progressive painless swelling, 26% having had symptoms for over 10 years. The proximal phalanx was the commonest site. Initial clinical misdiagnosis as ganglion, bursa, gout, rheumatoid arthritis and a cyst occurred in five patients. Radiologically most lesions showed bone expansion, cortical destruction and soft-tissue extension. The majority was of high histologic grade (Evan's grade 2 & 3) with extensive myxoid areas. Five out of eight patients who were originally treated by curettage or excision had local recurrences compared to none treated by ray resection or amputation of phalanx (P=0.002). None had metastases. The low risk of metastases despite the high histologic grade indicates that chondrosarcomas of the hand behave differently from chondrosarcomas elsewhere.

Extensive intraduct component in invasive duct carcinoma of the breast: prevalence and significance in a south Asian setting.

Extensive intraduct component (EIC) in invasive duct carcinoma is one of the main factors affecting local cancer recurrence and thereby a major consideration in breast conserving therapy. A retrospective study was undertaken to assess the prevalence of extensive intraductal component in a South Asian setting. 105 cases of invasive duct carcinoma reported at a University Pathology Department during a 75 month period from January 1992, were reviewed. 48.6 percent of all cases assessed had an intraductal component. 13.3 percent had an EIC. Of the seventy-two T1 and T2 tumours reviewed 5.6 percent showed EIC. The results of this study indicate that by virtue of its low prevalence. EIC in infiltrating ductal cancer is unlikely to be a major obstacle in the decision of breast conserving therapy in the South Asian region.

Prevalence of prostatic intraepithelial (PIN) in surgical resections.

OBJECTIVES: To determine the prevalence of prostatic intraepithelial neoplasia (PIN) in surgical specimens and assess its relationship to adenocarcinoma. METHOD: 205 surgical specimens (191) transurethral resections, 6 open prostatectomies, 8 needle biopsies) reported at the University Department of Pathology, Colombo over 64 months were reviewed. RESULTS: There were 170 benign hyperplasias and 35 adenocarcinomas. PIN I was present in 22.92% PIN II in 5.36% and PIN III in 7.32% of the specimens. 8.51%, 27.27% and 93.3% PIN I, PIN II and III were associated with invasive adenocarcinoma. Nine cases (4.39%) had high grade PIN (PIN II & III) in the absence of adenocarcinoma. CONCLUSION: PIN II & III were strongly associated with coexistent carcinoma but PIN I was not. The finding of high grade PIN in surgical biopsies with no obvious adenocarcinoma warrants examination of all available tissue and deep sections.