Immunopathology of Cutaneous Leishmaniasis in a Cohort of Sri Lankan Patients.

Introduction and objectives: Leishmania donovani is the causative organism of leishmaniasis in Sri Lanka. Studies on the immunopathology of leishmaniasis due to L. donovani are limited. The objective of this study was to describe the immunopathological characteristics of cutaneous leishmaniasis in a cohort of Sri Lankan patients. Methodology: Fifty skin biopsies of cutaneous leishmaniasis confirmed by detection of organisms by histology, culture, slit-skin smear, and/or polymerase chain reaction were reviewed. The inflammatory infiltrate was characterized by immunohistochemical staining for CD4, CD8, CD20, and CD68. Associations and correlations between immunohistochemical staining pattern and the parasitic load, and patterns of inflammation were determined. Results: The majority of biopsies showed a CD8+/CD4- T lymphocyte predominant infiltrate (84%, n = 42). A CD68 predominant infiltrate was seen in 16%(n = 8). The mean percentage of CD8+, CD4+, CD20+, and CD68+ inflammatory cells in the biopsies were 56.1% (SD = 16.5%), 2.6% (SD = 4.5%), 12.3% (SD = 10.9%), and 25.7% (SD = 15.8%) respectively. There was no association between the predominant inflammatory cell and the degree of inflammation (P = .173), presence of high RPI (P = .922), MRI(P = .367) or presence of granuloma (P = .247).The percentage of CD4+ cells showed a positive correlation with granuloma formation (Correlation coefficient = .411, P = .03). The percentage of CD20+ cells in the infiltrate showed a positive correlation with the degree of inflammation (Correlation coefficient = .491, P = .02) and the RPI (Correlation coefficient = .334, P = .018). Discussion and Conclusion: Skin biopsies from cutaneous leishmaniasis due to L. donovani infection showed a CD8+/CD4- predominant infiltrate. This is similar to the findings of studies on cutaneous leishmaniasis due to some other species and suggests that the cytotoxic T cell response plays a role in infections due to L. donovani.

Solid pseudopapillary neoplasm of the pancreas with multiple liver metastases successfully managed with staged resection.

Due to the rarity of the disease, there are no guidelines or consensus for the management of solid pseudopapillary neoplasm of the pancreas with liver metastasis. We describe a patient with solid pseudopapillary neoplasm of the pancreas with multiple liver metastases who was successfully managed with staged resection. A previously healthy 50-year-old female presented to the clinic with dull epigastric pain. The contrast-enhanced computed tomography showed a well-defined cystic lesion at the distal body and tail of the pancreas with multiple liver deposits. A core needle liver biopsy was suspicious of a hepatic epithelioid hemangioendothelioma. A distal pancreatectomy with splenectomy and a left hemi-hepatectomy were performed with a subsequent staged right posterior sectionectomy to address the inadequate future liver remnant. The final histology with immunohistochemistry revealed a pancreatic solid pseudopapillary neoplasm. The patient had satisfactory surgical and oncological outcomes with no recurrence. As these are slow growing tumours, appropriately spaced staged liver resection was feasible to allow hypertrophy of the liver remnant and physiological recovery of the patient. The discrepancy in the histology and cross-sectional imaging led to a pre-operative diagnostic dilemma, and the final diagnosis was reached after surgical resection. Thus, resectable metastatic solid pseudopapillary neoplasm of the pancreas may be offered a primary curative radical surgery before considering other treatment modalities.

Response and Survival Estimates of Patients With Plasma Cell Myeloma in a Resource-Constrained Setting Using Protocols From High-Income Countries: A Single-Center Experience From Sri Lanka.

PURPOSE: There is a significant disparity in global cancer care and outcome between countries. Progress in the treatment of symptomatic plasma cell myeloma (PCM) in high-income countries is not seen in low- and middle-income countries. MATERIALS AND METHODS: This is was a retrospective cohort study of all patients diagnosed with PCM between May 1, 2013, and September 30, 2021, at the first hemato-oncology center in Sri Lanka. We aimed to provide data on clinicopathologic characteristics, response, and survival estimates. RESULTS: A total of 79 patients with PCM received first-line therapy during the study period. The median age was 64 years, and approximately one third (33%) of patients were older than 70 years. There were 42 (53%) males and 37 females. Hypercalcemia, renal impairment, anemia, and bone disease were detected in 36.7%, 38%, 72.1%, and 81%, respectively. Thirty-nine, 34, and six patients received a combination of cyclophosphamide, thalidomide, and dexamethasone; bortezomib, thalidomide, and dexamethasone; and other treatments, respectively. The overall response rate (≥ partial response) was approximately 97% for both cyclophosphamide, thalidomide, and dexamethasone and bortezomib, thalidomide, and dexamethasone. Twenty-three (29%) of these patients died during the study period, but only 14 (18%) died due to PCM or associated sepsis. After a median follow-up of 40.6 months (range, 35.2-59.07 months), the median overall survival was 84.2 months (95% CI, 60.87 to not available). The 5-year estimated overall survival was 65%. CONCLUSION: To our knowledge, this is the only well-characterized study on long-term survival of patients with PCM in Sri Lanka. We have shown that it is possible to successfully apply Western treatment and supportive care protocols to the local population. These published data will help to benchmark and improve the treatment and develop blood cancer care in the local setting.

A diagnostic conundrum; Kimura's disease mimicking eosinophilic granulomatosis with polyangiitis.

Kimura's Disease (KD) is a benign, relapsing chronic inflammatory condition often seen in young Asian males, manifesting as recurrent swellings in skin and subcutaneous tissues especially in the head and neck region. Eosinophilic granulomatosis with polyangitis (EGPA) is a debilitating multisystem vasculitic condition which causes high morbidity due to cavitating lung lesions, neuropathy and renal impairment. Eosinophilia is common to both conditions. We, herein present a young Asian male with KD who presented with isolated recurrent nasopharyngeal mucosal swelling with eosinophilia. Biopsy of the lesion showed necrotizing vasculitis and eosinophilic granulomata mimicking EGPA. Nevertheless, he did not have any other characteristic systemic features of EGPA. Targeted evaluation through multidisciplinary approach helped secure the diagnosis of KD. KD has a wide range of presentation. The three cardinal histopathologic features in KD are eosinophilic inflammation, vascular proliferation and stromal fibrosis. However, vasculitis, granulomata and variable degree of necrosis can be present as in this case. He responded well to a course of steroids followed by Mycophenolate Mofetil. This minimized iatrogenic morbidity to the patient resulting from use of highly toxic immunomodulators which are not necessary in KD unlike in EGPA.

An epithelioid haemangioma of the ulnar artery masquerading as an aneurysm.

Epithelioid haemangiomas are rare benign vascular tumors that usually present as subcutaneous nodules in the head and neck area. Occasionally these tumors can arise in a peripheral artery. When it does so, it is often confused with an aneurysmal dilatation of the respective vessel. In these circumstances, surgical resection with vascular reconstruction is the preferred treatment option.

Applicability of protocols from high-income countries in a resource limited setting; real world data of histopathology, clinical features and long-term outcome of Hodgkin Lymphoma in Sri Lanka.

Background:: There is a significant disparity in global cancer care and out-come between countries. We aimed to provide data on characteristics, average cost of treatment and survival estimates in patients with Hodgkin Lymphoma in Sri Lanka. Methods: All patients diagnosed with Hodgkin Lymphoma between 01.05.2013 and 01.10.2020 were included in the analysis. Findings: Classical Hodgkin Lymphoma(cHL) diagnosed in 85%; 68% presented with B symptoms and 61% had advanced stage of disease. Treatment was discontinued by 23% either before or just after starting treatment of whom 72% percent were females. The complete response (CR) rate of patients who continued treatment was 86% while the estimated five-year survival rate is 92%. Seventeen percent of these patients died but only two percent due to Hodgkin Lymphoma or associated treatment in the group which continued treatment compared to 45% in the group who defaulted treatment (p-value 0.0002). Five-year survival rate of patients who defaulted treatment was 50% while patients who continued treatment have an estimated five-year survival rate of 90%. Average cost of first line treatment was between US$ 2280 and US$ 7642. First treatment failure may incur substantially higher health care costs. Interpretation: This is the only well characterized study on long-term survival of patients with Hodgkin Lymphoma in Sri Lanka. We have shown that it is possible to successfully apply western treatment and supportive care protocols to the local population. This published data will help to bench mark and improve the treatment and develop blood cancer care in the local setting.

Applicability of Western protocols in resource-limited setting: Real-world data of long-term outcome of intensive treatment of adult acute myeloid leukaemia in Sri Lanka.

There are no published data on long-term survival and applicability of treatment protocols from developed countries in acute myeloid leukaemia (AML) in Sri Lanka. Eighty-seven AML patients were reviewed; there were 56 newly diagnosed patients between 18 and 65 years. Thirty-one out of 33 who started treatment achieved complete remission after first cycle of treatment. The induction mortality was one of 33. Twelve out of 20 patients who completed treatment are alive at the time of analysis. The estimated 5-year overall survival rate is 0.629. Strict infection control and treatment and superior clinical experience may have contributed towards better outcome.

Histopathology of Cutaneous Leishmaniasis Caused by Leishmania donovani in Sri Lanka.

Cutaneous leishmaniasis (CL) is a neglected tropical disease that is gaining importance in Sri Lanka and internationally. The clinical presentation, pathology, and method of parasite elimination in CL vary according to the species. Leishmania donovani is the causative organism for leishmaniasis in Sri Lanka. This collaborative cross-sectional study describes the clinicopathological features of cutaneous leishmaniasis among personnel of the tri-forces serving in the North and East of the country. The histology of fifty cases of CL confirmed by at least two methods (slit skin smear, lesion aspirate, tissue impression, and histology) was reviewed. The parasitic load was assessed semiquantitatively. The histological features were correlated with the clinical presentation and organism load. The majority (89.8%; n = 44) presented with a single lesion mostly located in the upper limb (69.4%). The lesion types included papule (34.7%), nodule (32.7%), and an ulcer (30.6%). The evolution time of lesions averaged 31.55 weeks. Epidermal changes were observed in 49 of the biopsies and included hyperkeratosis (90.0%; n = 45), acanthosis (44.0%; n = 22), atrophy (34.0%; n = 17), and interface change (66%; n = 33). Dermal changes were seen in all cases and were characterized by a lymphohistioplasmacytic inflammatory infiltrate of variable intensity with ill-formed granuloma in 19 cases (38%) and well-formed epithelioid granulomas in 22 cases (44%). Focal necrosis was present in 20% (n = 10). Leishmania amastigote forms were observed in 88% (n = 44). Transepidermal elimination (P = 0.025), granuloma (P = 0.027) formation, and type of lesion (P = 0.034) were significantly associated with the organism load. Granuloma formation was associated with a reduction in organism load, indicating that the macrophage activation played an important role in the control of the organism.

Intrauterine Foley catheter for 48 versus 24 hours for cervical ripening: A randomized controlled trial.

OBJECTIVE: To compare the safety of keeping an intrauterine Foley catheter for 48 hours versus 24 hours for cervical ripening. METHODS: A randomized controlled trial was conducted at the De Soysa Hospital for Women, Sri Lanka from April 1 to December 31, 2014 (trial registration: SLCTR/2014/006). Low-risk women with a Bishop score ≤5 at 40 weeks + 5 days of gestation were allocated to either 24-hour (n=107; Group A) or 48-hour (n=94; Group B) groups. Proportions developing spontaneous onset of labor (SOL), neonatal status, pre- and post-procedure C-reactive protein (CRP), cervical smears, and placental histology in those who experienced SOL were compared. RESULTS: In Group A, 35 (32.7%) experienced SOL, against 54 (57.4%) in Group B (P<0.001, odds ratio 2.78, 95% confidence interval 1.56-4.93). There was no difference in mean length of active labor (7.48 vs 7.69 hours), cesarean delivery (16% vs 14%), bacterial vaginosis rates in post-induction cervical smear (10.3% vs 6.7%), mean CRP increase (4.08 vs 3.91 IU), evidence of chorioamnionitis (5.7% vs 11.1%), mean 1 and 5-minute Apgars, number of neonates with pyrexia (8.4 vs 8.5%), and admission to the Special Care Baby Unit (15% vs 12.8%). CONCLUSION: Group B experienced a statistically significant increase in SOL, without increasing infectious and neonatal morbidity.

Clinicopathological patterns and outcomes of urothelial bladder malignancies in Sri Lankan patients.

INTRODUCTION: Studies on bladder cancer in Sri Lanka have shown varying results in relation to clinicopathological characteristics and data on outcomes is limited. This study was aimed to describe the clinicopathological characteristics and outcomes of histologically confirmed urothelial bladder malignancies and to compare with previous studies. METHODS: A retrospective analysis of prospectively collected data of 314 newly diagnosed primary bladder malignancies between January-2007 and January-2017, was performed. After excluding the non-urothelial cancers, 289(92%) urothelial cancers (males=245, 84.8%, mean age = 65.4±SD10.9 years) were analysed. Data on clinical presentation, cystoscopic findings, histopathology and outcomes were studied. RESULTS: The majority (87.9%, n=254) presented with haematuria with a median duration of symptoms of 1 month. Non-muscle invasive cancers were seen among 64.4% (pTa:n=87(30.1%),pT1:n=99(34.3%)). The pT1 high grade (pT1-HG) tumours were seen in 17.5%. Muscle invasive bladder cancer (MIBC) were seen in 35.6%(n=103). The majority were high grade tumours (n=156,54%). Urothelial MIBC were significantly associated with solid tumours (p<0.001), high grade (p<0.001) and size>3cm (p<0.001). Comparison with previous studies showed a decline in the proportion of MIBC while the pT1-HG tumours are on the rise. Of those followed up, 52.5% developed recurrences with a median duration of 4 months (interquartile range (IQR): 3-12 months). Eighteen (9%) progressed to a higher stage with a median duration of 17 months (IQR:3.75-41.75). CONCLUSIONS: Urothelial cancer in the study population was 92%. Higher proportion of MIBC, high grade tumours and pT1-HG tumours were noted. The recurrence rate was high. Future studies should focus on the causative factors for this trend.

Idiopathic Scrotal Calcinosis: A Case Report of a Rare Entity.

Scrotal calcinosis is a benign condition where multiple calcified nodules are found within the dermis of the scrotal skin. It is a rare condition which is usually asymptomatic and has no clear aetiology although several theories have been proposed in the aetiopathogenesis. We report a 55-year-old man with extensive scrotal calcinosis. Surgical excision of the affected scrotal skin was curative.

Large schwannoma of the femur - a common tumor at an unusual site: a case report and review of the literature.

BACKGROUND: Schwannomas are benign nerve sheath tumors and are most frequently encountered as soft tissue tumors of peripheral nerves of the head and neck or the extensor extremities. Osseous involvement is very uncommon with fewer than 200 cases described in the world literature, the majority of which arise in the skull (including mandible), vertebrae, and sacrum. Long bone involvement is highly unusual and of the approximately 20 cases described thus far, only five have been documented to arise in the femur. We describe an unusually large schwannoma of the femur which was discovered incidentally and was diagnosed only after biopsy, given the rarity of this tumor at that particular site. Following prophylactic internal fixation and bone grafting, our patient remains well and disease-free, 2.5 years later. CASE PRESENTATION: A 56-year-old Sri Lankan woman was discovered to have a large lytic lesion in her lower femur on routine X-ray following a fall. A history and physical examination, along with selective imaging and tissue sampling, were necessary to arrive at the diagnosis of schwannoma of the femur. The clinical presentation, radiology, pathology, and surgical management are discussed and contrasted with the other five cases documented in the literature. The tumor was successfully treated with evacuation through a lateral surgical approach and internal fixation. She remains well and disease-free 2.5 years later. CONCLUSIONS: We present the case of an unusually large lytic lesion found incidentally in the femur of a 56-year-old woman, which was subsequently diagnosed to be a schwannoma on biopsy. Its exceptional rarity in long bones makes it less likely to be considered in an initial differential diagnosis, and we stress the importance of tissue biopsy for diagnosis.

Neurofibroma invading into urinary bladder presenting with symptoms of obstructed defecation and a large perineal hernia.

BACKGROUND: Pelvic floor hernias pose a diagnostic and a treatment challange. Neurofibromatosis is a rare systemic disease, and urinary tract involvement is rare. CASE PRESENTATION: Here we report a case of a 54-year-old female with multiple neurofibromatosis who presented with features of obstructed defecation and was found to have a large perineal hernia. At surgery, we found an unusual herniation of a large neuropathic bladder and rectum through a perineal defect. She underwent reduction cystoplasty and repair of the pelvic floor using a prolene mesh. Subsequent histopathological examination confirmed a large neurofibroma infiltrating the urinary bladder. CONCLUSION: Neurofibromatosis of the bladder is rare it should be considered as a differential diagnosis in patients presenting with symptoms of obstructed defecation.

Acute tubular necrosis in a patient with paroxysmal nocturnal hemoglobinuria.

Acute renal failure (ARF) is a well-recognized complication of paroxysmal nocturnal hemoglobinuria (PNH). The predominant mechanism is intravascular hemolysis resulting in massive hemoglobinuria ARF. We report a case of acute tubular necrosis (ATN) developed in the absence of overwhelming evidence of intravascular hemolysis in a 21-year-old man with anemia, who was eventually diagnosed to have PNH. The patient presented with rapidly deteriorating renal functions in the background of iron deficiency anemia, which was attributed to reflux esophagitis. There was no clinical or laboratory evidence of intravascular hemolysis. Renal biopsy revealed ATN with deposition of hemosiderin in the proximal tubular epithelial cells. Diagnosis of PNH was confirmed with a positive Ham's test and flow cytometry. Our case emphasizes the need to consider ATN as a possible cause for ARF in patients suspected to have PNH even in the absence of overwhelming evidence of intravascular hemolysis.

Comparison of the configuration of the posterior bifurcation of the posterior communicating artery between fetal and adult brains: A study of a Sri Lankan population.

OBJECTIVE: The purpose of this study was to examine the degree of contribution from the vertebrobasilar and carotid systems to the origin of the PCA in fetal autopsy brains of last trimester of pregnancy and to compare with published data on the configuration of adult and fetal brains in a population of Sri Lankan origin. MATERIALS AND METHODS: The external diameter of the PcomA, pre-communicating part (P1), and the post-communicating part (P2) of posterior cerebral artery (PCA) of 34 fetal brain in the last trimester of pregnancy (30 to 40 weeks of gestation) was measured using a stereomicroscope equipped with a micrometer calibrator. RESULTS: The blood supply to the occipital lobe mainly via the PCA was seen in 25 (59%) of fetal brains as compared to that in the literature 220 (93%) in adults brains and the blood supply to the occipital lobe mainly via the internal carotid artery (ICA) was seen in 16 (34%) of fetal brains as compared to 25 (7%) of adults brains (P < 0.0001), transitional configuration where the PcomA is equal in diameter to P1 segment of the PCA was seen in 5 (7.4%) of fetal brains and 8 (2%) of adults brains. CONCLUSIONS: The present study reveals that from the newborn to the adult there is shift from carotid system to the vertebrobasilar system, this justifies further studies on different racial and geographic regions which may give a clearer picture about the cerebral hemodynamics from childhood to adult.

Gastrointestinal stromal tumors (GIST): C-kit mutations, CD117 expression, differential diagnosis and targeted cancer therapy with Imatinib.

Gastrointestinal stromal tumors (GISTs) have been recognised as a biologically distinctive tumor type, different from smooth muscle and neural tumors of the gastrointestinal tract. They constitute the majority of gastrointestinal mesenchymal tumors. They are defined and diagnosed by the expression of a protooncogene protein called CD117 detected by immunohistochemistry. It is now believed that GISTs originate from gastrointestinal pacemaker cells known as interstitial cells of Cajal, that control gut motility or from a precursor of these cells. The identification of mutations mostly in exon 11 and to a lesser extent in exons 9 and 13 of the c-kit protooncogene coding for c-kit (CD117) in many GISTs, has resulted in a better understanding of their oncogenic mechanisms. The finding of remarkable antitumor effects of the molecular inhibitor, imatinib (Glivec trade mark ) in metastatic and inoperable GISTs, has necessitated accurate diagnosis of GISTs and their distinction from other gastrointestinal mesenchymal tumors. To achieve this, pathologists need to be familiar with the spectrum of histological appearances shown by GISTs and have a high index of suspicion for these tumors. This review summarises recent advances in knowledge regarding the histogenesis, pathology, molecular biology, genetics and differential diagnosis of GISTs and the basis for the novel targeted cancer therapy with imatinib.