M. V. C. De Silva

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=0.01 3), 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

Identification of poorly differentiated synovial sarcoma: a comparison of clinicopathological and cytogenetic features with those of typical synovial sarcoma.

Aims:  Poorly differentiated areas in synovial sarcomas (SS) are known to be associated with a poorer prognosis. The aim of our study was to describe the morphological spectrum of poorly differentiated synovial sarcomas (PDSS) and refine the criteria for their recognition.

Bladder cancer in Sri Lanka: Experience from a tertiary referral center

Background: Bladder cancer is one of the most common malignancies occurring worldwide. No published data exists on bladder cancer in Sri Lanka. The objective of the study was to determine the clinicopathological characteristics of histologically confirmed transitional cell carcinoma (TCC) of the bladder in Sri Lanka.

Fibromyxoid areas and immature osteoid are associated with recurrence of primary aneurysmal bone cysts.

Aims:  Primary aneurysmal bone cysts have a high recurrence rate following curettage. The aim of this study was to determine clinicopathological features associated with recurrence of aneurysmal bone cysts.

Incidence of bladder cancer in sri lanka: analysis of the cancer registry data and review of the incidence of bladder cancer in the South asian population.

Purpose To investigate the incidence of bladder cancer (BC) in Sri Lanka and to compare risk factors and outcomes with those of other South Asian nations and South Asian migrants to the United Kingdom (UK) and the United States (US). Materials and Methods The incidence of BC in Sri Lanka was examined by using two separate cancer registry databases over a 5-year period. Smoking rates were compiled by using a population-based survey from 2001 to 2009 and the relative risk was calculated by using published data. Results A total of 637 new cases of BC were diagnosed over the 5-year period. Sri Lankan BC incidence increased from 1985 but remained low (1.36 and 0.3 per 100,000 in males and females) and was similar to the incidence in other South Asian countries. The incidence was lower, however, than in migrant populations in the US and the UK. In densely populated districts of Sri Lanka, these rates almost doubled. Urothelial carcinoma accounted for 72%. The prevalence of male smokers in Sri Lanka was 39%, whereas Pakistan had higher smoking rates with a 6-fold increase in BC. Conclusions Sri Lankan BC incidence was low, similar to other South Asian countries (apart from Pakistan), but the actual incidence is likely higher than the cancer registry rates. Smoking is likely to be the main risk factor for BC. Possible under-reporting in rural areas could account for the low rates of BC in Sri Lanka. Any genetic or environmental protective effects of BC in South Asians seem to be lost on migration to the UK or the US and with higher levels of smoking, as seen in Pakistan.

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

Study Type – Prevalence (retrospective cohort)

A rare type of primary cutaneous amyloidosis: amyloidosis cutis dyschromica

Primary cutaneous amyloidosis, as it name denotes, is the deposition of amyloid in the previously normal skin without any systemic involvement. Several subtypes are described out of which macular and lichen are more common. The rare forms include nodular and tumifactive types. Amyloidosis cutis dyschromica is a rare form of primary cutaneous amyloidosis with only very few reported cases worldwide. The cardinal cutaneous feature is the generalized mottled hyper and hypopigmentation. Similar to other dyschromic conditions, this disease too is more common in the South East Asian region. Diagnosis of various types of dyschromatoses is often a challenge to the clinician. Therefore, the awareness of this rare entity among Dermatologists and Histopathologists, especially in the ethnic region where it is not commonly seen, is important.

Paraneoplastic pemphigus associated with inflammatory myofibroblastic tumor.

Case report A 23-year-old female patient diagnosed with erythema multiforme based on an oral biopsy performed 3 months previously presented with painful oral ulceration, a vesicular skin eruption and fever. The patient was treated with oral Acyclovir (Neon Antibiotics, Mumbai, India) for 7 days based on a clinical diagnosis of varicella. The patient had no past history of blistering disorders or oral ulcers. There was no history of loss of appetite, weight loss or other constitutional symptoms. There was no family history of autoimmune or bullous diseases. The patient continued to develop extensive stomatitis, especially involving the lips (Fig. 1), together with flaccid blisters and target lesions of the trunk and target lesions of the palms and soles, which later progressed to tense blisters. The nails became dystrophic with subungual pus formation and subsequent shedding. The patient had painful genital ulcers and erosive lesions of the eyelids with corneal ulceration. Systemic examination was unremarkable, with no lymphadenopathy, hepatosplenomegaly or abdominal masses. A biopsy of the skin lesion showed intraepidermal blister formation associated with suprabasal acantholysis. The dermis contained a mild perivascular lymphocytic infiltrate. Direct immunofluorescence of perilesional skin showed epidermal cell surface and basement membrane zone staining with IgG and C3. Indirect immunofluorescence showed circulating anti-IgG antibodies with a titre of 1/400 on normal skin, monkey esophagus and rat bladder substrates, consistent with paraneoplastic pemphigus. An ultrasound scan of the abdomen was performed in search of an underlying tumor. This revealed a retroperitoneal mass size 7.5 × 7 cm, anterior to and separate from the left kidney. This finding was later confirmed by a CT scan, which showed a well-defined, homogenous mass. An ultrasound guided tru-cut biopsy of the abdominal tumor showed a lesion composed of haphazardly arranged bland spindle cells intermixed with an intense inflammatory reaction rich in lymphocytes with a lesser number of plasma cells, eosinophils and occasional mast cells (Fig. 2). Immunohistochemistry showed positivity of the spindle cells for desmin and smooth muscle actin. There were CD68 +ve macrophages and S100 +ve dendritic cells. The lymphocytes comprised a mixture of B cells (CD20 +ve) and T cells (CD3 +ve). The spindle cells were negative for CD21, CD23, CD35, and ALK-1. The proliferative marker Ki-67 (MIB-1) showed moderate proliferative activity. The histology and immunohistochemical features were in keeping with the diagnosis of an inflammatory myofibroblastic tumor. Response to intravenous dexamethasone and cyclophosphamide pulse therapy was poor. The tumor could not be surgically removed owing to the poor general condition of

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.

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.