Angiomatoid fibrous histiocytoma: Clinicopathological spectrum of five cases, including EWSR1‑CREB1 positive result in a single case.

Background: Angiomatoid fibrous histiocytoma (AFH) is an unusual soft tissue tumor (STT), characterized by recurrences, but rarely metastasis. Later, certain molecular signatures have been identified underlying this tumor, which at times, is either underdiagnosed as a benign vascular tumor, or over diagnosed as a high‑grade pleomorphic sarcoma, including a malignant fibrous histiocytoma. Materials and Methods: Over a 14‑year‑period, five diagnosed cases of AFH were analyzed. Results: Five tumors occurred in three males and two females, over a wide age‑range (median = 21, mean = 30 years); mostly in the extremities (4) (80%). Microscopically, most tumors were circumscribed, comprising large, blood‑filed spaces with surrounding histiocytic cells and a “cuff” of lymphoplasmacytic cells. Three tumors revealed solid growth pattern with polygonal to spindle cells, including myxoid matrix in one of these tumors. On molecular analysis, this tumor exhibited EWS‑CREB transcript. Immunohistochemically, various tumors were positive for CD68 (n = 2/2), epithelial membrane antigen (n = 3/4), CD99/MIC2 (n = 2/3), and desmin (n = 1/4). All tumors were surgically excised. On follow‑up (n = 2), a single patient, who underwent wide‑excision was free‑of‑disease (24 months), while another patient had a recurrence 4 months post tumor excision. Conclusions: This forms as the first documented series on clinicopathological features of AFH, a rare STT, from our country. Significant clinicopathological features include younger age, extremities as commonest site and histopathological appearance of blood‑filled spaces with surrounding “cuff” of histiocytic cells and lymphocytes. Tumors with unusual histopathological tumor patterns require molecular confirmation. Surgical resection remains the treatment mainstay.

Intraosseous myoepithelioma: A rare, distinct tumor entity

Primary musculoskeletal myoepithelial tumors (METs) are distinctly rare tumors and are being increasingly recognized as a result of improved diagnostic criteria and objective confirmation with immunohistochemical markers, including epithelial markers. Recent studies have unraveled distinct molecular mechanisms underlying these tumors. Herein, we present our second diagnosed case of an intraosseous MET that occurred in the tibia of a 37-year-old lady. The case is discussed with regards to current clinicopathological perspectives on these rather uncommon tumors, including our personal experience.

Immunohistochemical validation of TLE1, a novel marker, for synovial sarcomas.

Background & objectives: Logistic and financial constraints limit application of several available immunohistochemical (IHC) markers and molecular analysis in every case of synovial sarcoma, diagnosed in our settings. Recently, TLE1 has been recognized as a robust IHC marker for diagnosing a synovial sarcoma. Here, we present IHC features of synovial sarcomas, including TLE1 expression in these cases and in some other tumours. Methods: Conventional sections from 42 synovial sarcomas (30 retrospective & 12 prospectively diagnosed) were subjected to TLE1 IHC staining, including 21 tumours confirmed with molecular testing. TLE1 immunostaining was graded from 0, 1+, 2+, 3+, with 2+ or 3+ grades interpreted as positive staining. Results: Of the 42 tumours, 26 (61.9%) were of monophasic spindle cell type, 13 biphasic type (30.9%), two (4.7%) calcifying type and remaining one (2.3%) was a poorly differentiated synovial sarcoma. On immunohistochemistry (IHC), tumours were positive for epithelial membrane antigen (EMA) (26/34, 76.4%), cytokeratin (CK)7 (6/10, 60%), CK/MNF116 (6/21, 28.6%), B cell lymphoma 2 (BCL2) (36/37, 97.3%), cluster of differentiation molecule 99 (MIC2) (23/31, 74.1%) and transducin-like enhancer of split 1 (TLE1) (40/42, 95.2%), while negative for CD34 in all 21 tumours, wherever performed. TLE1 was also positive in tumour controls, including schwannomas (5/5, 100%), neurofibromas (2/2, 100%), malignant peripheral nerve sheath tumors (2/12, 17%) and Ewing sarcomas (4/10, 40%). TLE1 sensitivity for diagnosis of synovial sarcomas was 95.2 per cent. Its overall specificity was 63.7 per cent, whereas with regards to tumors forming its closest differential diagnoses, its specificity was 72 per cent. Interpretation & conclusions: Although molecular confirmation is the diagnostic gold standard for synovial sarcoma, TLE1, in view of its high sensitivity may be a useful marker within the optimal IHC panel comprising EMA, BCL2, MIC2, CD34 and CK7, especially on small biopsy samples, for substantiating a diagnosis of synovial sarcoma. Awareness of TLE1 expression in other tumours and its correct interpretation are necessary.

Malignant transformation in a hybrid schwannoma/perineurioma: Addition to the spectrum of a malignant peripheral nerve sheath tumor.

Benign nerve sheath tumors include schwannomas, neurofibromas and perineuriomas. The malignant counterpart of a nerve sheath tumor is designated as a malignant peripheral nerve sheath tumor (MPNST). Lately, benign nerve sheath tumors comprising more than one component have been described, including hybrid schwannomas/perineuriomas. However, malignant transformation in a hybrid schwannoma/perineurioma has not been documented so far. Herein, we present a rare case of a young adult male who presented with a soft tissue mass in his right thigh that was excised elsewhere and submitted to us for histopathological review. One of the tissue sections displayed histopathological features of a hybrid schwannoma/perineurioma, including alternate arrangement of benign schwann and perineurial cells, reinforced with S100-P and epithelial membrane antigen positivity, respectively, along with low MIB1 and negative p53 immunostaining. The other two tissue sections showed a spindly sarcomatous tumor that was immunohistochemically positive for S100-P, CD34, p53 and exhibited high MIB1 (30-40%). Diagnosis of a MPNST arising in a hybrid schwannoma/perineurioma was made. This unusual case forms yet another addition to the spectrum of a MPNST.

Malignant peripheral nerve sheath tumors: Clinicopathological profile of 63 cases diagnosed at a tertiary cancer referral center in Mumbai, India.

Background: A malignant peripheral nerve sheath tumor (MPNST) is a rare sarcoma, characterized by an aggressive course and forms a diagnostic challenge, in view of its varied histomorphology. The present study is a comprehensive analysis, including histopathological spectrum of 63 MPNSTs that forms a substantial study from an Indian perspective. Materials and Methods: Clinicopathological features of 63 MPNSTs, diagnosed during a period from January 2002 to December 2006, at a tertiary cancer referral center in Mumbai, India, were analyzed. Statistical analysis was carried out using SPSS (version 14) and STRATA. Difference in events was noted in 50 cases with selected variables. Disease free survival (DFS) was calculated by Kaplan-Meir analysis at the end of 1 year. Results: More cases were identified in > 30 years age (36 cases, 57.14%) group; in men (46 cases, 73%), and were deep-seated (38, 60.3%). Ten cases (15.9%) showed stigmata of multiple neurofibromatosis type 1. Average tumor (T) size was 9.9 cm, with 72.9% cases having T size > 5 cm. More cases were of high grade (56, 88.8%) and high stage (22, 34.9%). Histopathologically, most cases showed hypo- and hypercellular areas (marbleized appearance) of doubly indented spindle cells. Two cases showed epithelioid differentiation. Heterologous elements in the form of osteoid, chondroid, pigmented neuroectodermal (1 case), glandular (1 case) and rhabdomyoblastic differentiation (1 case) were identified in 14 cases (22.2%). S-100 protein positivity was noted in 38/54 cases (70.3%). Maximum cases (45, 71.4%) underwent surgery, including wide excisions and amputations (R0) in 20 cases, marginal excisions (R1) in 4, and intracapsular excision (R2) in 1 case. Nineteen cases underwent adjuvant treatment. A total of 29 cases (46%) showed recurrences and 22 (34.9%) showed multifocality and/or metastasis. Four patients succumbed to the disease in 1 year. The DFS was 53.1%. Cases ≤30 years of age (P- value = 0.007), T size > 5 cm, and with high grade (P = 0.18) and stage (P = 0.00) showed more recurrences, metastasis, and death. Conclusions: A MPNST has multifaceted histomorphology. Its objective identification necessitates the incorporation of clinicopathological features and IHC with S-100 protein. Younger age, high grade and stage, and increased T size significantly relate to aggressive disease. Wide excision forms the optimal treatment with options of adjuvant CT/RT in individual cases.

A giant solitary fibrous tumor of the pleura: Diagnostic implications in an unusual case with literature review.

A solitary fibrous tumor of the pleura (SFTP) is an uncommon tumor, in contrast to a relatively common mesothelioma in pleura. Its average size varies from 6 to 8 cm. We report herein a case of a giant SFTP in a 53-year-old man who presented with cough since five years along with chest pain on the left side and progressive dyspnea since two months. Radiological findings revealed a large pleural mass measuring 25 cm in its largest dimension, filling the pleural cavity with effusion. Biopsy showed a spindle cell tumor with areas of dense sclerosis. Subsequent excision unraveled a large multinodular, grey-white tumor, histologically, composed of spindle cells in a 'patternless' arrangement in dense collagenous stroma with areas of hyalinization. Focal areas showed hypercellularity with atypia and mitoses, but less than 4/10 High-Power Field, unassociated with necrosis. On immunohistochemistry, tumor cells showed diffuse positivity with vimentin, CD34 and BCL2 along with cytoplasmic positivity for MIC2 (CD99), whereas cytokeratin, EMA, calretinin and HBME-1 were negative. Diagnosis of an SFTP was substantiated over a close differential of a desmoplastic mesothelioma. In view of atypical features, a close follow-up of the case was recommended.

Chondrosarcoma of bone: does the size of the tumor, the presence of a pathologic fracture, or prior intervention have an impact on local control and survival?

AIMS AND OBJECTIVES: We studied 45 patients with chondrosarcoma, without metastasis at diagnosis, who were surgically treated between January 2000 and December 2004 to evaluate the risk factors associated with local recurrence and metastasis. MATERIALS AND METHODS: Fourteen (31%) patients had had some major prior intervention, either in the form of an open biopsy or a curettage / unplanned excision, before presenting to us. Eight patients had pathologic fractures at presentation. None of the patients received adjuvant chemotherapy or radiotherapy. The follow-up duration ranged from 8-75 months. All survivors had a minimum follow-up of 36 months (range 36-75 months). RESULTS: There were 11 grade 1 (24.5%), 23 grade 2 (51%), and 11 grade 3 (24.5%) chondrosarcomas. Thirty-two (71%) patients had tumors that were larger than 8 cm in the greatest dimension. Margins were adequate in 31 patients. Twenty-five patients had disease relapse; there were four local failures, nine distant failures, and 12 combined failures. At the time of the last review, 12 patients had died, 11 were alive with disease, and 22 were free of disease. The cumulative event-free survival was 44% and the overall survival was 73%. CONCLUSION: Grade of tumor, size of tumor, and adequacy of resection might be important predictors of outcome. Local recurrence is a prelude to distant metastasis and portends poor ultimate survival. The presence of a pathological fracture could indicate biologically aggressive disease, and limb salvage in these cases should be advised with caution. Even in cases where there has been a prior unplanned intervention, local control can be achieved by subsequent adequate resection.

Epithelioid sarcoma of the foot with subsequent lesion in hand: metastatic lesion or second primary?

Epithelioid sarcomas (ES) are rare tumors of soft tissue that have a propensity to occur in the extremities. Epithelioid sarcomas are known to metastatise to draining lymph nodes and commonly to the lungs. Herein, a case of epithelioid sarcoma which recurred in an unusual site namely the distal phalanx of left middle finger, six months post amputation of the primary lesion in the left foot is being reported. The ipsilateral inguinal lymph node showed metastatic deposits. The tumor at both these sites had similar histology and an identical immunohistochemical (IHC) pattern showing reactivity to cytokeratin (CK), epithelial membrane antigen (EMA), vimentin (Vim) and CD34. This case is presented to record an unusual occurrence of ES in the distal phalanx of middle finger with an ES of foot. The metastasis of ES to the distal acral bones has not been documented till date.

Metastatic adenocarcinoma presenting as an inguinal hernia: a case report and review of literature.

A 61 year old man presented with an inguinal hernia with no other significant symptoms. Histopathological examination of the hernial sac revealed metastatic deposits of a mucin secreting adenocarcinoma which was confirmed by subsequent tumor marker levels. Patient was put on chemotherapy for disseminated adenocarcinoma and is tolerating it well. This case emphasizes the need to carefully examine all hernial sacs received for pathological examination.

CD10 in diffuse uterine leiomyomatosis: a case report along with a few comments on histogenesis.

Diffuse uterine leiomyomatosis (DUL) is a rare entity with an unknown etiopathogenesis. A 24 years old female presented with abdominal discomfort and menorrhagia. Clinical and ultrasonographic examination revealed an enlarged uterus. The hysterectomy specimen showed a symmetrically enlarged uterus with a bosselated external surface. The cut surface showed multiple nodules of varying sizes diffusely involving the myometrium. Microscopically, the nodules were leiomyomas of varying degrees of cellularity. Some of the leiomyomas showed an increased vascularity either in the form of congeries of blood vessels with a lobular arrangement or occasionally as foci of 2-3 vessels. The vessels were surrounded by whorls of spindle cells. On immunohistochemistry the leiomyomas expressed vimentin, smooth muscle actin (SMA), desmin and CD10: the cells whorling around the blood vessels expressed vimentin, SMA and focally desmin and were negative for CD10 and HMB-45. The aim of this paper is to document that CD10 is expressed in diffuse uterine leiomyomatosis and discuss the histogenesis of DUL.

Mesenchymal chondrosarcoma: a series of 23 cases.

A total of 23 cases of mesenchymal chondrosarcoma were studied from the histopathology records spanning 23 years. There were 16 men and 7 women afflicted with this tumor and their mean age was 28.1 years. The radiological features, histology and treatment outcomes have been studied. Osseous and extra-osseous mesenchymal chondrosarcomas are compared and the differential diagnosis discussed.

Langerhans' cell histiocytosis: a clinicopathological study of 50 cases.

To analyze the clinicopathologic features and outcome of patients with Langerhans cell histiocytosis (LCH). Fifty cases of LCH accrued over a 15-year period were analyzed and classified as having unifocal, multifocal, or multisystem disease. Events regarding progression, relapse, or death were noted. The 50 cases comprised of 34 men and 16 women. 92% of the patients were less than 15 years of age and 46% were less than 2 years. Involvement by LCH was unifocal in 22, multifocal in 8, and multisystem in 20. Bone was the commonest site (92%), followed by lymph node (30%). The histological features were relatively uniform regardless of the clinical severity, and consisted of Langerhans cells, eosinophils, histiocytes, plasma cells, giant cells and fibrosis. The treatment consisted of surgery, chemotherapy, and/or radiotherapy. Response to treatment was poor in patients with multisystem disease. The histology of LCH is very characteristic and patients with age less than 2 years are more likely to have increased risk or morbidity and mortality, due to widespread disease.

Chondroblastoma of bone--not a " benign disease": clinico-pathologic observations on sixty cases.

Chondroblastomas (CBL) account for less than 1% of all bone tumors. A 46 year review (1955-2000) of bone tumors yielded 60 cases of CBL. This paper reviews their histology, radiology, clinical presentation and emphasizes that this seemingly benign lesion is capable of aggressive behaviour. Histopathology slides and radiographs of sixty patients were studied and clinical details and follow-up were obtained. There were 44 males and 16 females, aged between 10 to 30 years. Long bones were involved in 81.4% of the cases, tibia being the commonest site. Symptoms comprised pain (60%), local swelling (25%) and joint symptoms (5%) or a combination of these. Radiologically, an oval sharply demarcated lytic lesion predominantly in the epiphysis was noted in 50% of the cases. On microscopy all lesions revealed chondroblasts having irregular grooved nuclei and osteoclasts with 80% of the tumors showing chondroid differentiation and calcification. Treatment comprised curetting (34 cases), wide excision (21 cases), radical excision (1 case) and was unknown in 4 cases. Follow-up ranging from 2 to 26 years was available in 83.3% of the patients; six (10%) had local recurrence (at 6 months, 8 months, 1 year, 2 years, 3 years and 5 years), two (3.3%) developed lung metastasis (synchronous in one and at 18 months in the other) and spontaneous malignant transformation occurred in one (1.4%) patient after 9 years; subsequent to three local recurrences. CBL, though seemingly benign, can behave in an aggressive manner. Since there are no reliable histological features to predict biologic behaviour, regular long term follow-up is recommended.

Rosette formation in osteosarcoma.

Rosette formation is a rare, recently reported variation in osteogenic sarcoma and is thought to be associated with a poor prognosis. We report two cases of rosette forming osteosarcoma, one with poor response and other with total necrosis following chemotherapy. Pathologists should be aware of rosette formation in osteosarcoma to avoid misdiagnosis as other rosette forming tumors of bone especially PNET/Ewings sarcoma. In our opinion rosettes in an osteosarcoma should be documented both from a differential diagnostic point of view and also to elucidate definitive prognostic implications.

Epithelioid hemangioendothelioma of bone--a clinicopathologic and immunohistochemical study of 7 cases.

Epithelioid hemangioendothelioma is a rare vascular tumor of bone. Between 1987-1999, seven cases of epithelioid hemangioendothelioma were recorded. The histopathological evaluation was done with hematoxylin and eosin stain and immunohistochemical stains along with the analysis of clinical data and X-ray findings. There were 4 males, 3 females between 15 to 48 years of age with complaints of pain and swelling. Long bones were involved in five of the seven patients and one was multifocal. Radiologically all seven patients showed osteolytic lesions. The histologic hall mark was the presence of eosinophilic, epithelioid cells with intracytoplasmic vacuoles. The tumor may be histologically confused with metastatic carcinoma, chondromyxoid fibroma and osteogenic sarcoma. Immunohistochemical reactivity was as follows: Vimentin (6/6 cases), Factor VIII related antigen (4/6 cases), Ulex Europeaus (5/6 cases), CD31 (3/5 cases), CD34 (3/5 cases), epithelial membrane antigen (1/6 cases), cytokeratin (none). Treatment comprised curettage (4 cases), wide excision (2 cases), below knee amputation (1 case) and post operative radiotherapy (2 cases). At follow-up, (available in 4 patients) two were without disease at 18 months and 120 months. Of the remaining two, one developed local recurrence after 36 months; while the other died of lung metastasis (18 months). A lytic bone shadow, the presence of plump eosinophilic often vacuolated cells on a myxoid background and immunohistochemistry together help in the correct recognition of this tumor.