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.

Pasteurization of bone for tumour eradication prior to reimplantation – An in vitro & pre-clinical efficacy study.

Background & objectives: In current era of limb-salvage therapy, pasteurization of bone sarcomas is receiving growing attention as a potential extracorporeal treatment and cost-effective alternative to allografts and radiation before surgical reimplantation. Detailed in vitro and in vivo pre-clinical study to evaluate efficacy of pasteurization to eradicate malignant cells has not been reported yet. The present study was carried out to assess the efficacy of pasteurization to kill tumour cells both in vitro and in vivo. Methods: Surgically resected specimens of osteosarcomas (n=4) were cut into equal halves and one section was pasteurized by heating at 60°C to 65°C for 40 min. Paired samples before and after pasteurization were studied in vitro for DNA ploidy, evaluation of histological change and elimination of mitotic activity. These tissues were transplanted in immune-deficient NOD-SCID mice to evaluate effect on tumour-generating ability, presence of human nuclei, osteopontin and cytokine/chemokines released in tumour-transplanted mice. Results: Non-pasteurized tumour samples had viable tumour cells which exhibited significant growth in culture, increased proliferative ability and clonogenic potential while respective pasteurized tumour tissues did not grow in culture and did not exhibit clonogenicity. Flow cytometry revealed that propidium iodide positive dead cells increased significantly (P<0.01) post pasteurization. Seven of 12 non-pasteurized tumour transplanted mice demonstrated tumour-forming ability as against 0 of 12 in pasteurized tumour transplanted mice. Solid tumour xenografts exhibited strong expression of anti-human nuclei and osteopontin by immunohistochemistry as well as secretary human interluekin-6 (IL-6) while pasteurized mice failed to express these markers. Interpretation & conclusions: This study has provided a basis to establish pasteurization as being efficacious in ensuring tumour eradication from resected bone tumour specimens. Pasteurized tumour bearing bone can thus safely be used to reconstruct large defects after tumour resection.

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.

Splenic angiomatoid nodular transformation in child with inflammatory pseudotumor-like areas.

Reports of sclerosing angiomatoid transformation (SANT) in the pediatric age group are rare. We present a case of SANT in an 11-year-old child with a history of trauma presenting with rapidly growing splenic lesion since 2 months. A partial splenectomy revealed a well-demarcated nodular lesion 5 × 4 × 4 cm with central area of fibrosis. Most part of the lesion showed ill-defined nodules or diffuse areas of plump epithelioid appearing endothelial units that marked with CD31, but the internodular stroma was inflammatory pseudotumor (IPT)-like with a mitotic count of 1-2/10 hpf. The angiomatoid nodules were diffusely positive for CD31, CD163, and CD68; however, they were negative for CD34, CD30, smooth muscle actin, and CD8. Epstein-Barr virus-encoded RNA in situ hybridization (EBER-ISH) was negative. The MIB1 labeling was fairly high in the IPT area but low in the angiomatoid areas. After the diagnosis of SANT, the patient has had an uneventful follow-up for more than 3 years since surgery. The morphologic findings in the case being discussed reaffirm the finding that SANT may have an IPT component and it can be seen even in pediatric age group.

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.

Primary endobronchial synovial sarcoma confirmed by SYT-SSX1 fusion gene transcript by reverse transcriptase polymerase chain reaction.

Primary sarcomas of lung are rare compared to metastatic sarcomas. Herein, we report a rare case of primary pulmonary synovial sarcoma with polypoid endobronchial growth in a 35-year-old lady who presented with cough and dyspnea. A malignant pulmonary tumor was suspected and left pneumonectomy was performed. Grossly, a non-encapsulated polypoidal endobronchial tumor measuring 6 cm in greatest diameter, with a solid, tan-white cut surface was identified. Microscopically, tumor was characterized by a proliferation of oval to spindle-shaped cells arranged in sheets and fascicles. Focal hemangiopericytomatous pattern was noted. Immunohistochemically, tumor cells were positive for vimentin, BCL-2, MIC-2 and calponin and focally positive for pancytokeratin and epithelial membrane antigen. A subsequent molecular analysis performed using reverse transcriptase-polymerase chain reaction with RNA extracted from paraffin-embedded tissue, revealed SYT/SSX1 fusion gene which confirmed the diagnosis of synovial sarcoma. The utility of immunohistochemistry and molecular techniques in diagnosis of such a rare case is stressed and the relevant literature is discussed.

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.

Immunohistochemistry in surgical pathology practice: a current perspective of a simple, powerful, yet complex, tool.

Immunohistochemistry (IHC) is a powerful tool in the surgical pathologists' armamentarium. The requests for IHC and the list of monoclonal antibodies have increased tremendously in the past decade. Issues concerning technical reproducibility, uniformity of interpretation, inter-laboratory comparability, and quality assurance are assuming greater importance due to the increased availability of IHC and its impact on diagnosis and therapy. An attempt has been made to give a current perspective of this simple and yet, in some aspects, a complex tool.

Calcifying fibrous pseudotumour: a case report.

Calcifying fibrous pseudotumor with psamomma bodies (CFT) is a distinct soft tissue lesion characterized by lymphoplasmacytic collections in a rich collagenous background with abundant calcification. It was recognized first in peripheral axial soft tissues. Recently reports of this lesion in an intrabdominal location have raised speculations about it being a myofibroblastic tumor. However, this has been discounted on several objective grounds. Its recognition is important for the excellent prognosis, once adequately excised. This case report exemplifies one such case with a long-term disease-free follow-up and discusses the other clinicopathologic entities it may be confused with.

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.

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.

Well-differentiated adenocarcinoma of the rectosigmoid colon associated with psammoma bodies: a case report.

This report documents an unusualfinding of scattered psammomatous-type calcification in a well-differentiated adenocarcinoma of the rectosigmoid colon in a 54-year-old woman. The clinical relevance of this histologic feature is discussed, in light of review of the literature.

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.