Grossing and reporting of bone tumor specimens in surgical oncology: Rationale with current evidence and recent updates.

Primary bone tumors, including sarcomas, are rare tumors and require a multidisciplinary approach, including inputs from a radiologist, pathologist, medical oncologist, and surgical and radiation oncologist, for optimal management. Over the years, there has been a paradigm shift toward the treatment of bone sarcomas, from radical resections to conservative surgical procedures, to achieve improved clinical and functional outcomes. This has led to receiving and processing various types of specimens in orthopedic oncopathology. Grossing and reporting of bone tumors require expertise. This review focuses upon the types of biopsies, grossing techniques of various specimens in orthopedic oncology and reporting, with rationale and recommendations from pathologists, actively involved in reporting and pursuing a special interest in bone tumors, based on current evidence. Furthermore, there is a section on some of the updates in the diagnosis of bone tumors, based on the recent fifth edition of the World Health Organization classification of tumors of soft tissues and bone.

Grossing and reporting of a soft tissue tumor specimen in surgical pathology: Rationale, current evidence, and recommendations.

Soft tissue tumors, including sarcomas are complex and diagnostically challenging tumors. This is as a result of their heterogeneity and overlapping clinicopathological, immunohistochemical and also molecular features, the latter to some extent. More than 80 types of sarcoma have been described. Current management, which is best offered at centers with active multidisciplinary care, is based on balancing oncologic and functional outcomes in such cases. This has transcended into the types of specimens received for grossing these rather uncommon tumors. Over the years, diagnostic specimens have reduced in their sizes from, open biopsies to core needle biopsies. These specimens need to be adequately and judiciously triaged for ancillary techniques, such as molecular testing. Conservative surgeries have led to resected specimens for marginal assessment. Lately, post neoadjuvant (chemotherapy or radiation therapy)-treated resection specimens of soft tissue sarcomas are being submitted for surgical pathology reporting. This article focuses on the grossing of soft tissue tumors, including sarcomas, in terms of types of specimens, grossing techniques including rationale, tissue triage, reporting, and recommendations from the surgical pathologists actively engaged in reporting musculoskeletal tumors, based on current evidence.

Clinicopathologic features of four rare types of chordomas, confirmed by brachyury immunostaining.

BACKGROUND: A wide clinicopathologic spectrum of a chordoma exists. Brachyury constitutes as its most useful diagnostic immunohistochemical (IHC) marker. METHODS: During a 7-year-period, 4 unusual histopathologic types of chordomas were identified. Immunohistochemistry was performed by polymer technique. RESULTS: Clinicopathologic features of the 4 cases are as follows: Cases 1 and 2: Two tumors occurred in the sacrococcygeal and lumbosacral regions of a 42-year-old male and a 34-year-old female, respectively. Histopathologic examination showed areas of classical chordoma; juxtaposed to a high-grade, spindle cell sarcoma. By IHC, cytokeratin (CK), epithelial membrane antigen (EMA), S-100 protein, and brachyury were found to be distinctly positive in the differentiated chordomatous areas. Both these cases were diagnosed as dedifferentiated chordomas. The first patient, postresection and adjuvant radiation therapy (RT), died after 14 months of therapy. Case 3: A 58-year-old male presented with pain in his sacral region and urinary incontinence. Imaging disclosed a sacral mass. Histopathologic examination showed physaliphorous cells intimately admixed with, markedly pleomorphic cells, scattered mitotic figures, and focal tumor necrosis. By IHC, the tumor cells were positive for CK, AE1/AE3, S-100 protein, brachyury, and INI1/SMARCB1. The diagnosis of a poorly differentiated chordoma was offered. Despite surgical resection and adjuvant RT, the patient died within 18 months. Case 4: A 58-year-old male presented with a soft tissue lesion in his left leg. Histopathologic examination showed physaliphorous cells, embedded in a myxohyaline stroma. By IHC, the tumor cells were positive for EMA, S-100 protein, brachyury, and INI1. Diagnosis of an extra-axial, soft tissue chordoma was offered. CONCLUSIONS: These four unusual chordomas, confirmed by brachyury immunoexpression, constitute as one of the first such documentation from our country, revealing a wide clinicopathologic spectrum of chordomas. Dedifferentiated and poorly differentiated chordomas are associated with an aggressive clinical course. Further diagnostic implications are discussed herewith.

Clinicopathological Features of a Series of 27 Cases of Post-Denosumab Treated Giant Cell Tumors of Bones: A Single Institutional Experience at a Tertiary Cancer Referral Centre, India.

Giant cell tumor of bone (GCTB) is mostly a benign tumor, but associated with recurrences and metastasis. Lately, denosumab is being utilized in the treatment of certain GCTBs. Twenty-seven tumors, analyzed in the present study, occurred in 16 males and 11 females (M: F = 1.45:1), in the age-range of 16 to 47 years (mean = 29.5, median = 29). Most tumors were identified in the tibia(6) and femur(6), followed by the humerus(3), radius(3), pelvis(3), fibula(3), sacrum(1), metacarpal(1) and metatarsal(1) bones. There were 18(66.6 %) primary and 9(33.3 %) recurrent tumors. Exact tumor size (19 cases) varied from 3.7 to 15 cm (mean = 7.8, median = 6.4). Eight of the 19 tumors (42.1 %) had size more than or equal to 8 cm. On histopathologic examination of post-denosumab treated specimens, more than half cases (15)(55.5 %) revealed complete absence of osteoclast-like giant cells (OCLGs) and 12 cases revealed residual OCLGCs. In addition, there was replacement by fibro-osseous tissue, including reactive woven bone or osteoid in most cases, followed by variable amount of spindle cells, hyalinisation, fibrosis and chronic inflammatory cells, including lymphocytes, macrophages and plasma cells. Post-treatment follow-up (25 cases, 92.5 %), over 7-27 months duration (median = 18), revealed 20 cases continuously disease-free. Five patients developed recurrences at 9, 12, 13, 14 and 18 months, respectively. Out of these, who underwent repeat surgical intervention, 4 patients are alive with no evidence of disease and a single patient, planned for a second surgery, is alive-with-disease. Denosumab was mostly offered to patients with large sized, borderline salvageable tumors, in order to decrease the morbidity of index surgical procedure, that led to disappearance of OCLGCs in most cases. Post-denosumab treated GCT cases appear as low grade osteosarcomas on histopathologic examination, but lack the clinical behaviour of an osteosarcoma, therefore may be considered as pseudo malignant bony lesions.

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.

Osteoclast-rich, proximal-type epithelioid sarcoma: clinicopathologic features of 3 unusual cases expanding the histomorphological spectrum.

Epithelioid sarcoma (ES) displays a wide clinicopathologic spectrum. On histopathology, osteoclast-like giant cells have been rarely described in these tumors. A 45-year-old gentleman presented with a perineal swelling of 6-month duration. Radiologic imaging disclosed a large, highly vascular tumor mass in his perineal region that was diagnosed elsewhere as pigmented villonodular synovitis. A 58-year-old lady presented with a recurrent tumor in her right inguinolabial region for which she underwent multiple tumor resections in the past. A 33-year-old lady presented with a right inguinal swelling of 1-month duration that was diagnosed elsewhere as a non-Hodgkin lymphoma on fine needle aspiration cytology. Histopathologic examination of tumors in all the 3 cases revealed epithelioid to "rhabdoid-like" cells arranged in a diffuse pattern interspersed with many osteoclast-like giant cells. The first tumor also revealed focal pseudoangiosarcomatous areas and heterotopic bone formation. By immunohistochemistry, tumor cells in all 3 cases were positive for AE1/AE3, epithelial membrane antigen, and CD34 and were completely negative for INI1/SMARCB1. CD68 immunostaining in 2 tumors highlighted osteoclast-like giant cells. Osteoclast-rich, proximal-type ES are unusual tumors, indicative of an expanding spectrum of ESs. Awareness of this histopathologic pattern and diagnostic confirmation with necessary immunohistochemical stains is crucial to avoid misinterpretation, as these tumors are clinically aggressive and are treated with wide local excision and optional adjuvant radiation therapy.

Clinicopathological spectrum of a series of Merkel cell carcinomas diagnosed at a tertiary cancer referral center in India, with current concepts.

Merkel cell carcinoma (MCC) is a rare, clinically aggressive primary cutaneous neuroendocrine carcinoma. The present series describes clinicopathological features of 16 MCCs diagnosed at a tertiary cancer referral center. Sixteen MCCs occurred in 10 men and 6 women (M/F = 1.6:1), between the ages 37 and 74 years (mean, 58.3; median, 58.6), commonly in lower extremities (7) (43.7%) and head and neck sites (5) (31.2%), followed by upper extremities (3) (18.7%) and abdominal wall (1). Tumor size varied from 0.5 to 9.9 cm. Histopathologically, most tumors were composed of round to oval cells, mostly arranged diffusely with hyperchromatic nuclei, including "sudden" pleomorphism in some tumors. Variable features included coexisting Bowen disease (2/16), along with squamous, pseudoglandular, and rhabdomyoblastic dedifferentiation, all in a single tumor. Immunohistochemically, tumor cells were positive for at least a single epithelial marker in all 16 cases (100%) cases, including CK20, mostly paranuclear "dot-like" (12/13, 92.3%); CK (8/9, 88.8%), AE1/AE3 (3/3, 100%), and CK7 (1/6, 16.6%), along with neuroendocrine markers (16/16, 100%), including synaptophysin (11/13, 84.6%), chromogranin (12/15, 80%), and CD56 (4/4, 100%). Among other immunohistochemical markers, positive CKIT/CD117 was positive in 3 of 3 tumors. Surgical resection was performed in 11 (100%) of 11 cases, with adjuvant chemotherapy offered in a single case. Two cases with large-sized tumors, along with another case developed lymph node metastasis, including 1 who later developed pulmonary metastasis. Two patients were free of disease and 2 were alive with disease. Merkel cell carcinomas exhibit a diverse histopathological spectrum, including coexisting Bowen disease and, rarely, rhabdomyoblastic dedifferentiation, in some cases. Optimal immunohistochemical markers include CK20, synaptophysin, chromogranin, and CD56 for a timely diagnosis. Surgical resection is the treatment mainstay. Large-sized tumors and MCCs showing dedifferentiation portend a relatively more aggressive clinical course. Other recent developments in this tumor are discussed herewith.

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.

Clinicopathological and molecular spectrum of ewing sarcomas/PNETs, including validation of EWSR1 rearrangement by conventional and array FISH technique in certain cases.

Over the years, a wide clinicopathological spectrum has been identified within Ewing family of tumors (EFTs). As these tumors are chemosensitive, their correct and timely identification is necessary. The aims of this study were (1) to present the diverse clinicopathological and molecular profile of EFTs in our settings, (2) to identify a pragmatic approach for diagnosing EFTs, especially for application of ancillary techniques, namely RT-PCR for specific transcripts (EWS-FLI1, EWS-ERG) and FISH for EWSR1 gene rearrangement, in certain cases and (3) to show the utility of tissue microarray in establishing a new FISH test. Fifty-eight EFTs were identified in 38 males and 20 females within an age-range of 1-65 years (median, 16), mostly in lower extremities (14) (24.1 %). Therapeutically, most patients underwent neoadjuvant chemotherapy with subsequent surgery. Histopathologically, diagnosis of EFTs was initially offered in 41/58 (70.6 %) tumors. On review, 59 % tumors showed diffuse pattern, while 41 % displayed rosettes. Immunohistochemically, tumor cells were mostly diffusely positive for CD99 (48/52) (92.3 %); FLI-1 (17/18) (94.4 %); variably for BCL2 (16/18) (88.8 %), synaptophysin (6/20) (35 %), S100-P (2/7) (28.5 %), CD56 (2/5) (40 %), NSE (2/5) (40 %), calponin (3/4) (75 %), EMA (5/24) (20.8 %) and CK (3/24) (12.5 %), the latter two mostly focally. Fifty five tumors were EWS-FLI1 positive, while a single tumor was EWS-ERG positive. Sensitivity for PCR was 61 %. EWSR1 rearrangement was detected by FISH in 12/13 Ewing sarcomas/PNETs. Sensitivity for EWSR1 test was 92.3 % and specificity was 100 %. Thirty-eight tumors, including 14 molecular confirmed EFTs and 21 other tumors were tested for EWSR1 rearrangement. Among 21 unrelated tumors, EWSR1 rearrangement was detected in few myoepithelial tumors, occasional desmoplastic small round cell tumor and an extraskeletal myxoid chondrosarcoma. Further, a tissue microarray with a separate set of 8 EFTs, confirmed at another laboratory was analysed for validation of EWSR1 rearrangement test. 23/28 (82.1 %) tissue cores of the tissue microarray, stained by FISH were interpretable, including EWSR1 rearrangement, detected in 20/28 tissue cores; not detected in 3 liver cores and uninterpretable in 5 (17.8 %) cores. Classical EFTs can be diagnosed with diffuse, membranous CD99 positivity, intranuclear FLI1 positivity and LCA negativity in malignant round cells. In unconventional cases, it is indispensable to reveal the concomitant fusion m-RNA by RT-PCR. In case of negative molecular results, it is necessary to prove EWSR1 rearrangement by FISH. These tests should be interpreted with clinicopathological correlation. Tissue microarrays for FISH are useful during validation of a new test, especially when sarcomas like EFTs show less genetic heterogeneity within tumor cells.

Immunohistochemical validation of INI1/SMARCB1 in a spectrum of musculoskeletal tumors: an experience at a Tertiary Cancer Referral Centre.

The purpose of this study was to evaluate and validate immunohistochemical (IHC) expression of INI1/SMARCB1 in various musculoskeletal tumors in the light of the established literature. Twenty-seven cases of epithelioid sarcoma (ES); 4 of extrarenal rhabdoid tumor (ERRT) of soft tissue and 97 other tumors, including 16 cases of synovial sarcoma (SS), were evaluated for IHC expression of INI1 on formalin-fixed, paraffin-embedded tissue sections of various biopsies. Out of 128 tumors, INI1/SMARCB1 staining was completely lacking in cases of ES (23/27) (85.1%), ERRTs (4/4) (100%), myoepithelial tumors (4/14) (28.5%) and in (1/16) (6.2%) cases of SS. Fourteen out of 15 SSs displayed a reduced staining pattern. Other 67 studied tumors were INI1-positive. Sensitivity for complete INI1 negativity in ES was 85.1%, and specificity with respect to its differentials, excluding ERRTs, was 94.8%. Complete lack of INI1 immunostaining in most ESs indicates its value as a diagnostic marker for ESs, including those occurring at rare sites; in ERRTs and in some myoepithelial tumors, within an appropriate clinicopathological context, in all kinds of biopsies. ES, at least in some cases, is immunohistochemically the most closely related tumor to an ERRT. A unique pattern of reduced INI1 expression in a SS is useful during triage of some cases for molecular testing. Its expression should be interpreted in the tumor cells, rather than intermixed stromal cells and or inflammatory cells that retain INI1 expression.

Metastatic paraganglioma presenting as a primary shoulder mass.

Paragangliomas uncommonly metastasize, including to the bones, wherein these tumors are designated as malignant paragangliomas. A 56-year-old man presented with pain and immobility in his right arm for 1 year. He had a history of controlled hypertension and diabetes mellitus for 2 years. He had also been taking anti-anxiety medications for 25 years. His shoulder imaging revealed an expansile, lytic, destructive lesion in the glenoid cavity, measuring 4.6 × 3.9 × 3.2 cm, involving the adjacent bones and soft tissues. A whole-body PET-CT scan revealed a hypermetabolic destructive mass in the right glenoid cavity and another lesion in his abdomen in the aortocaval region. Initial biopsy and subsequent scapular resection microscopically revealed a multinodular tumor with polygonal cells arranged in a nesting and diffuse pattern, in a vascularized and sclerotic stroma. Tumor cells displayed moderate to abundant, eosinophilic to clear cytoplasm, fine nuclear chromatin, focal intranuclear inclusions, and scattered mitotic figures. Immunohistochemically, tumor cells were positive for vimentin, synaptophysin, chromogranin, and CD56 and negative for AE1/AE3, CK, EMA, CD10, SMA, Melan A, HMB-45, desmin, and S100-P. Biopsy of the abdominal mass revealed foci of tumor cells resembling the scapular tumor. Diagnosis of a malignant paraganglioma was finally offered. The patient's post-operative blood pressure is controlled. Currently, his urinary vanillylmandelic acid and metanephrine levels are normal. He is asymptomatic 11 months post-surgery and is on follow-up. This unusual case is presented to increase a diagnostic index of suspicion for a malignant paraganglioma, including at unconventional musculoskeletal sites. The diagnostic challenge and therapeutic implications are discussed herewith.

Histopathological, immunohistochemical and molecular spectrum of myoepithelial tumours of soft tissues.

Primary soft tissue myoepithelial tumours (METs) are rare. Recent studies have shown EWSR1 rearrangement in certain METs. We present clinicopathological, immunohistochemical and molecular features of 14 primary soft tissue METs. Fourteen tumours, five benign and nine malignant, occurred in 12 men and two women, with an age range of 18-60 years (mean, 39.2); in upper extremities, four (29 %); chest wall, three (21 %); paraspinal region, three (21 %); pelvis, two (14 %) and lower extremities, two (14 %). Tumour size varied from 2 to 21.6 cm (mean, 8.7). Microscopically, most tumours were at least focally circumscribed. Morphological heterogeneity was noted, commonest patterns being cord-like and diffuse arrangement of polygonal cells in a myxoid stroma. By immunohistochemistry, tumours were positive for epithelial membrane antigen (EMA) (10/12, 83 %), cytokeratin (CK)/MNF116 (3/12, 25 %), p63 (7/10, 70 %), CD10 (4/6, 67 %), calponin (6/6, 100 %), S-100P (11/13, 85 %), glial fibrillary acidic protein (GFAP) (6/12, 50 %), smooth muscle actin (SMA) (3/9, 33 %), INI1/SMARCB1 (6/10, 60 %), brachyury (0/11), CD34 (0/5) and vimentin (4/4, 100 %), implying 93 % positivity for at least one epithelial marker. EWSR1 gene rearrangement was detected in 3/6 (50 %) METs (one benign and two malignant) and in an eccrine porocarcinoma which was included for reasons of comparison. Outcome details were available for six patients all surgically treated; three tumours (two malignant and one benign) resected with unknown marginal status recurred; two patients died and a single patient with myoepithelial carcinoma, who underwent a wide excision, is disease-free. This study illustrates the wide morphological spectrum of soft tissue METs, including benign and malignant subtypes. EMA and S-100P are optimal markers that should be supplemented with broad spectrum keratins, such as AE1/AE3, along with p63, GFAP and calponin in case of need but the results must be correlated with morphological features. Brachyury is useful in separating parachordoma/myoepithelioma from chordoma. EWSR1 rearrangement mostly occurs in METs that are deep-seated, irrespective of benign or malignant behaviour. Most malignant METs are INI1 negative.

Unusual clinical behaviour of thymoma with recurrent myasthenia gravis.

A 58-year old man with thymoma and myasthenia gravis (MG) had undergone thymectomy 8 years ago with histopathologically confirmed non-invasive WHO-type AB thymoma. After 5 years of complete remission, symptoms of MG resurfaced, and a recurrent anterior mediastinal mass was detected for which he received radiotherapy. He presented to us 3 years later with productive cough and exertional dyspnoea; the positron emission tomography-computed tomography scan revealed a metabolically active pulmonary nodule in the right lung as the only site of disease for which a right lower lobectomy was done. Microscopy established an intrapulmonary WHO-type B2 thymoma and the patient is currently asymptomatic on steroids, anticholinesterase and immunosuppressant therapy. We discuss the variable and unpredictable course of thymomas; the possibility of transformation into more aggressive types with each recurrence, association with recurrent MG post-thymectomy and presentation several years later with metastatic disease.

Lymphangiosarcoma arising after 33 years within a background of chronic filariasis: a case report with review of literature.

Cutaneous angiosarcoma or lymphangiosarcoma represents an uncommon aggressive tumor known to arise on a background of chronic lymphedema secondary to various etiologies, principally following surgery or irradiation. There have been rarely reported cases of angiosarcoma following infective conditions that eventuate with lymphatic stasis. We report a case of angiosarcoma arising after 33 years within a background of filariasis. Awareness of this association can lead to early diagnosis and appropriate treatment of this potentially fatal malignant tumor.

Alveolar soft part sarcoma 'revisited': clinicopathological review of 47 cases from a tertiary cancer referral centre, including immunohistochemical expression of TFE3 in 22 cases and 21 other tumours.

BACKGROUND: Alveolar soft part sarcoma accounts for 0.5-1.0% of soft tissue sarcomas in the United States. At our Hospital, it constitutes 1.8% of the newly diagnosed soft tissue sarcomas. Lately, TFE3 has been found to be a useful immunohistochemical marker for diagnosing this sarcoma. METHODS: We reviewed 47 cases of alveolar soft part sarcoma that were either treated at Tata Memorial Hospital, Mumbai, India, or were referred in consultation from various parts of India. TFE3 immunohistochemical staining was performed on 22 alveolar soft part sarcomas and on 21 other tumours. RESULTS: Unlike most other large series, 58% of patients were males and 40% were females. The ages ranged from 2 to 54 years (median 24 years). Tumours were located in the deep soft tissues of lower extremities (54%), upper extremities (13%), head and neck (11%), retroperitoneum (10%), chest wall (6%), pelvis (4%), and were positive for TFE3 (20/22, 91%), desmin (3/18, 16%), myoglobin (1/6, 17%) and smooth muscle actin (1/9, 11%). TFE3 was positive in tumour controls that comprised paragangliomas (3/4), translocation related renal cell carcinoma (1/1), adrenocortical carcinoma (1/3) and granular cell tumour (1/3). Treatment consisted of primary surgical excision, metastatectomy, chemotherapy and radiotherapy. Seven tumours (24%) recurred locally and 21 of 29 (72%) metastasised, mainly to the lungs. Follow-up information (5-108 months, median 27.5 months) was available for 22 patients. No patients died in the relatively short follow-up period. CONCLUSIONS: TFE3 is a useful immunohistochemical marker for diagnosis of an alveolar soft part sarcoma. Awareness of other tumours expressing TFE3 is vital. Alveolar soft part sarcoma has a high metastasis rate but relatively good short-term survival. Surgical excision with follow-up forms the present management.

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.

Radioprotective effect of Ocimum sanctum and amifostine on the salivary gland of rats after therapeutic radioiodine exposure.

The current study investigated the radioprotective effect of Ocimum sanctum on the salivary gland of rats administered radioiodine ((131)I) and compared its efficacy with a known radioprotectant, amifostine. The experimental rats were divided in four groups and sacrificed in three different batches at 1, 3, and 6 months of time interval after 18.5 MBq/100g (i.p.) (131)I exposure. Six months duration batch received (131)I exposure twice with the gap of 3 months. Two groups of experimental rats were presupplemented with O. sanctum (40 mg/kg for 5 days, orally) and amifostine (200 mg/kg, s.c) before (131)I exposure separately. Increased Technetium-99m-pertechnetate ((99m)TcO(4)(-)) uptake at 30 minutes post injection in salivary glands of only (131)I exposed rats may imply delay in clearance at 6 months of exposure in comparison to their counterparts sacrificed at 1 month. Parotid gland histology showed atrophy with lipomatosis in only (131)I exposed rats at 3 and 6 months of duration. O. sanctum and amifostine presupplemented and subsequently exposed to (131)I rats at 3 and 6 months duration exhibited comparable histopathology with controls. Our study indicates possible radioprotective effect of O. sanctum and amifostine against high-dose (131)I exposure.