Assessing Morphological Diversity of Acinic Cell Carcinoma of Salivary Glands at a Tertiary Care Hospital in Pakistan.

INTRODUCTION: Acinic cell carcinoma (AciCC) is a rare clinical entity and a salivary gland malignancy. It is associated with wide histological variations in the cytomorphological patterns. METHODS: Sixty cases diagnosed as AciCC from 2002 to 2023 were assessed for diverse cytomorphological patterns. RESULTS: The mean age of patients at the time of diagnosis was 44.35±16.8 years ranging from 15 to 81 years. Females comprised 58.3% for a F: M ratio of 1.4:1. Fifty three cases (88.3%) occurred in the parotid gland, two cases in the nasal region (3.3%), and one case each in the soft plate and upper lip (1.7%). The location of the remaining three cases was not specified. The most common presenting complaint was a well-defined facial swelling associated with pain. The average tumor size was 3.8±1.9 cm. The most predominant architectural pattern was solid (83.3%) followed by microcystic (60%), then follicular (41.7%), papillary cystic (14.3%), and tubulocystic (28.6%), and AciCC with de-differentiation/high-grade transformation was reported in three cases (5%). In 83.3% of the cases (50 out of 60), we noticed a mixture of two or more growth patterns. Other degenerative changes included prominent lymphoid stroma, hemorrhage, and cystic change. CONCLUSION: Awareness and recognition of diverse cytomorphological patterns of AciCC, especially in institutions of a developing country where there is limited availability of highly specific and sensitive immunohistochemical stains or molecular diagnostics, are crucial and essential.

Role of SOX10 Immunohistochemical Expression in Diagnosing Triple Negative Breast Cancer and Its Correlation With Clinicopathological Features.

BACKGROUND: Triple-negative breast cancer (TNBC) poses a diagnostic challenge for histopathologists due to the reduced frequency of breast-specific markers. SOX10 has emerged as a useful diagnostic marker for TNBC. The aim of our study was to determine the frequency of SOX-10 immunohistochemical (IHC) expression in our cohort and assess its correlation with clinicopathological and histological features. MATERIALS AND METHODS: We included 72 primary TNBC cases. Specimens included tru-cut biopsies and excision specimens. We stained whole slide sections of these specimens with SOX10 antibody and calculated its frequency (%) of expression and H-score. We applied the chi-square test to assess the correlation between SOX10 expression and clinicopathological and histological features such as the patient's age, specimen type, tumor size, histological type, histological grade, nuclear pleomorphism, mitotic count, tumor-infiltrating lymphocytes (TILs), necrosis, calcification, lymphovascular invasion (LVI), lymph node involvement, T stage, and N stage. RESULTS: SOX10 expression was observed in 42 (58.3%) cases with a median H-score of 57.5. The expression was significantly higher in tru-cut biopsy specimens as compared to excision specimens (73.5 vs 41.7%) and TILs negative tumors as compared to TILs positive tumors (64.3% vs 27.3). Metaplastic carcinoma showed reduced expression when compared with non-metaplastic tumors (35.7% vs 63.8%), but statistical significance was not achieved. No correlation was observed with the patient's age, tumor size, histological type, histological grade, nuclear pleomorphism, mitotic count, necrosis, calcification, LVI, lymph node involvement, T stage, and N stage. CONCLUSION: SOX10 was expressed in more than half of the TNBC cases of our study which not only highlights its diagnostic utility but advocated its application in combination with other breast-specific markers. The expression didn't correlate with the majority of clinicopathological and histological features, but correlation with tru-cut biopsy specimens and absence of TILs draws attention towards possible roles of proper fixation and host immunity, respectively.

Clinicopathological features of dysembryoplastic neuroepithelial tumor: a case series.

BACKGROUND: Dysembryoplastic neuroepithelial tumors are rare benign supratentotrial epilepsy-associated glioneuronal tumors of children and young adults. Patients have a long history of seizures. Proper surgical resection achieves long term seizure control. We describe the clinicopathological features of dysembryoplastic neuroepithelial tumor cases reported in our practice and review the published literature. METHODS: All cases of Pakistani ethnicity were diagnosed between 2015 and 2021 were included. Slides were reviewed and clinicopathological features were recorded. Follow-up was obtained. Extensive literature review was conducted. RESULTS: Fourteen cases were reported. There were 12 males and 2 females. Age range was 9-45 years (mean 19 years). Majority were located in the temporal and frontal lobes. Duration of seizures prior to resection ranged from 2 months to 9 years with mean and median duration of 3.2 and 3 years, respectively. Histologically, all cases demonstrated a multinodular pattern, specific glioneuronal component, and floating neurons. Simple and complex forms comprised seven cases each. No significant nuclear atypia, mitotic activity, or necrosis was seen. Ki-67 proliferative index was very low. Cortical dysplasia was noted in adjacent glial tissue in four cases. Follow-up ranged from 20 to 94 months. Seizures continued following resection in all but one case but were reduced in frequency and intensity. In one case, seizures stopped completely following surgery. CONCLUSION: Clinicopathological features were similar to those in published literature. However, a marked male predominance was noted in our series. Seizures continued following resection in all but one case but were reduced in frequency and intensity. This series will help raise awareness among clinicians and pathologists in our part of the world about this seizure-associated tumor of children and young adults.

Events in CNS Tumor Pathology Post-2016 WHO CNS: cIMPACT-NOW Updates and Other Advancements: A Comprehensive Review Plus a Summary of the Salient Features of 2021 WHO CNS 5.

Introduction: The 2016 World Health Organization Classification (WHO) of Tumors of the Central Nervous System (CNS) represented a major change. It recommended an "integrated diagnosis" comprising histologic and molecular information facilitating a more precise diagnosis of specific CNS tumors. Its goal was to provide greater diagnostic precision and reproducibility resulting in more clinical relevance and predictive value, ultimately leading to better patient care. Advances in molecular classification, mostly resulting from DNA methylation array profiling of CNS tumors, were occurring at a very rapid pace and required more rapid integration into clinical practice. Methods: cIMPACT-NOW updates and other recent papers plus salient features of 2021 WHO CNS5 in this comprehensive write-up were reviewed. Results: CNS tumor classification needs to be updated at a rapid pace and mechanisms put into place to guide diagnosticians and clinicians in the interim period if major changes in the classification of tumor types came to light. Recognizing the need to integrate these into clinical practice more rapidly and without inordinate delay, the International Society of Neuropathology (ISN) 2016 sponsored an initiative called cIMPACT-NOW. Discussion and/or Conclusion: Goal of cIMPACT-NOW was to provide clarification regarding contentious issues arising in the wake of the 2016 WHO CNS update as well as report new advancements in molecular classification of CNS tumors and new tumor entities emerging as a result of these advancements. cIMPACT-NOW updates: It thus laid the foundation for the 5th edition of the WHO Classification of CNS tumors (2021 WHO CNS 5). We have discussed cIMPACT updates in detail in this review. In addition, molecular diagnostics including DNA methylation-based classification of CNS tumors and the practical use of molecular classification in the prognostication and treatment of CNS tumors is discussed. Finally, the salient features of the new CNS tumor classification are summarized.

Anaplastic Large-cell Lymphoma Involving Gastrointestinal Tract: A Clinicopathologic Study of 25 Cases of a Rare Tumor at a Rare Site.

Background. Anaplastic large-cell lymphoma (ALCL) is an uncommon lymphoma divided into anaplastic lymphoma kinase (ALK) positive, ALK negative, and breast implant-associated (BIA) ALCL. Gastrointestinal tract involvement is very rare and may be difficult to diagnose. Its recognition is crucial as prognostic ramifications are different. Objectives. To describe clinicopathological features of ALCL involving the gastrointestinal tract. Materials and Methods. Slides were reviewed. Diagnosis was confirmed. Histological and immunohistochemical features were described. Results.Twenty-five tumors were diagnosed during the study period. Ages ranged from 14 to 65 years (mean 41 years). Mean age for ALK-negative and ALK-positive patients were 49 and 17 years, respectively. Twenty-one were males and 4 were females. Eighteen involved small intestine. Mean tumor size was 4.2 cm. All showed diffuse sheets of large anaplastic cells with pleomorphic nuclei, abundant pink cytoplasm, and strong positivity for CD30. Epithelial membrane antigen was positive in 17 tumors and keratin was negative in all. Eighteen tumors were ALK negative. Out of 14 patients with follow-up, 12 died within a few months of diagnosis. Seven had stage IE, 5 had stage IIE, and 2 had stage IV disease. Two patients were alive at 35 and 60 months. Twelve received chemotherapy. Conclusion. A marked male predominance was noted. Small intestine was the commonest site of involvement. Majority were ALK negative. ALK-negative tumors occurred in older patients and ALK positive in younger patients. Prognosis was poor. ALCL should be included in the differential diagnosis of anaplastic epithelioid cell neoplasms in the gastrointestinal tract.

Amplification of the PLAG-family genes-PLAGL1 and PLAGL2-is a key feature of the novel tumor type CNS embryonal tumor with PLAGL amplification.

Pediatric central nervous system (CNS) tumors represent the most common cause of cancer-related death in children aged 0-14 years. They differ from their adult counterparts, showing extensive clinical and molecular heterogeneity as well as a challenging histopathological spectrum that often impairs accurate diagnosis. Here, we use DNA methylation-based CNS tumor classification in combination with copy number, RNA-seq, and ChIP-seq analysis to characterize a newly identified CNS tumor type. In addition, we report histology, patient characteristics, and survival data in this tumor type. We describe a biologically distinct pediatric CNS tumor type (n = 31 cases) that is characterized by focal high-level amplification and resultant overexpression of either PLAGL1 or PLAGL2, and an absence of recurrent genetic alterations characteristic of other pediatric CNS tumor types. Both genes act as transcription factors for a regulatory subset of imprinted genes (IGs), components of the Wnt/ß-Catenin pathway, and the potential drug targets RET and CYP2W1, which are also specifically overexpressed in this tumor type. A derived PLAGL-specific gene expression signature indicates dysregulation of imprinting control and differentiation/development. These tumors occurred throughout the neuroaxis including the cerebral hemispheres, cerebellum, and brainstem, and were predominantly composed of primitive embryonal-like cells lacking robust expression of markers of glial or neuronal differentiation (e.g., GFAP, OLIG2, and synaptophysin). Tumors with PLAGL1 amplification were typically diagnosed during adolescence (median age 10.5 years), whereas those with PLAGL2 amplification were diagnosed during early childhood (median age 2 years). The 10-year overall survival was 66% for PLAGL1-amplified tumors, 25% for PLAGL2-amplified tumors, 18% for male patients, and 82% for female patients. In summary, we describe a new type of biologically distinct CNS tumor characterized by PLAGL1/2 amplification that occurs predominantly in infants and toddlers (PLAGL2) or adolescents (PLAGL1) which we consider best classified as a CNS embryonal tumor and which is associated with intermediate survival. The cell of origin and optimal treatment strategies remain to be defined.

TFG::MET-rearranged soft tissue tumor: A rare infantile neoplasm with a distinct low-grade triphasic morphology.

This article presents 2 cases of TFG::MET-rearranged mesenchymal tumor, an extremely rare molecular subset among an emerging group of mesenchymal neoplasms with kinase gene (NTRK, BRAF, RET and others) alterations. Both tumors were congenital, occurred in female patients and presented as huge masses on the trunk and thigh, measuring 18 and 20 cm in the largest dimension. Both cases showed identical areas with a distinctive triphasic morphology resembling fibrous hamartoma of infancy (FHI), consisting of haphazardly arranged ovoid to spindled cells traversed by variably cellular and hyalinized fascicles admixed with (most likely non-neoplastic) adipose tissue. In other areas, a high-grade infantile fibrosarcoma/malignant peripheral nerve sheath tumor-like (IFS/MPNST-like) morphology was present in both cases. While the first case co-expressed CD34 and S100 protein, the other case did not. When combined with the three previously reported MET-rearranged cases (of which two harbored TFG::MET fusion), 3/5 and 3/4 of MET-rearranged and TFG::MET fusion-associated tumors, respectively exhibited similar triphasic FHI-like low-grade morphology. This points toward the existence of a relatively distinct morphological subset among kinase-fusion-associated tumors which seems to be strongly associated with MET fusions. It seems some of these low-grade cases may transform into a high-grade variant with IFS/MPNST-like morphology as has been observed in other tumors with kinase gene fusions. While most cases seem to follow an indolent clinical course, the recognition of these tumors is clinically relevant as MET tyrosine kinase inhibitors might represent an effective treatment option for clinically aggressive or unresectable cases.

Comprehensive Molecular Profiling of Sinonasal Teratocarcinosarcoma Highlights Recurrent SMARCA4 Inactivation and CTNNB1 Mutations.

Sinonasal teratocarcinosarcoma (TCS) is a rare tumor defined by intermixed neuroepithelial, mesenchymal, and epithelial elements. While its etiology was historically ambiguous, we recently reported frequent SMARCA4 loss by immunohistochemistry, suggesting that TCS might be related to SMARCA4-deficient sinonasal carcinomas. However, other molecular alterations including CTNNB1 mutation have been reported in TCS, and its full genetic underpinnings are unclear. Here, we performed the first comprehensive molecular analysis of sinonasal TCS to better understand its pathogenesis and classification. We collected 30 TCS including 22 cases from our initial study. Immunohistochemical loss of SMARCA4 was seen in 22 cases (73%), with total loss in 18 cases (60%). ß-catenin showed nuclear localization in 14 cases (64%) of the subset tested. We selected 17 TCS for next-generation sequencing with enrichment for partial or intact SMARCA4 immunoexpression. We identified inactivating SMARCA4 mutations in 11 cases (65%) and activating CTNNB1 mutations in 6 cases (35%), including 5 cases with both. Of 5 cases that lacked SMARCA4 or CTNNB1 mutation, 2 harbored other SWI/SNF complex and Wnt pathway alterations, including 1 with SMARCB1 inactivation and 1 with concomitant APC and ARID1A mutations, and 3 had other findings, including DICER1 hotspot mutation. These findings confirm that SMARCA4 inactivation is the dominant genetic event in sinonasal TCS with frequent simultaneous CTNNB1 mutations. They further underscore a possible relationship between TCS and sinonasal carcinomas with neuroendocrine/neuroectodermal differentiation. However, while SMARCA4 and ß-catenin immunohistochemistry may help confirm a challenging diagnosis, TCS should not be regarded as a molecularly defined entity.

Intracranial mesenchymal tumors with FET-CREB fusion are composed of at least two epigenetic subgroups distinct from meningioma and extracranial sarcomas.

'Intracranial mesenchymal tumor, FET-CREB fusion-positive' occurs primarily in children and young adults and has previously been termed intracranial angiomatoid fibrous histiocytoma (AFH) or intracranial myxoid mesenchymal tumor (IMMT). Here we performed genome-wide DNA methylation array profiling of 20 primary intracranial mesenchymal tumors with FET-CREB fusion to further study their ontology. These tumors resolved into two distinct epigenetic subgroups that were both divergent from all other analyzed intracranial neoplasms and soft tissue sarcomas, including meningioma, clear cell sarcoma of soft tissue (CCS), and AFH of extracranial soft tissue. The first subgroup (Group A, 16 tumors) clustered nearest to but independent of solitary fibrous tumor and AFH of extracranial soft tissue, whereas the second epigenetic subgroup (Group B, 4 tumors) clustered nearest to but independent of CCS and also lacked expression of melanocytic markers (HMB45, Melan A, or MITF) characteristic of CCS. Group A tumors most often occurred in adolescence or early adulthood, arose throughout the neuroaxis, and contained mostly EWSR1-ATF1 and EWSR1-CREB1 fusions. Group B tumors arose most often in early childhood, were located along the cerebral convexities or spinal cord, and demonstrated an enrichment for tumors with CREM as the fusion partner (either EWSR1-CREM or FUS-CREM). Group A tumors more often demonstrated stellate/spindle cell morphology and hemangioma-like vasculature, whereas Group B tumors more often demonstrated round cell or epithelioid/rhabdoid morphology without hemangioma-like vasculature, although robust comparison of these clinical and histologic features requires future study. Patients with Group B tumors had inferior progression-free survival relative to Group A tumors (median 4.5 vs. 49 months, p = 0.001). Together, these findings confirm that intracranial AFH-like neoplasms and IMMT represent histologic variants of a single tumor type ('intracranial mesenchymal tumor, FET-CREB fusion-positive') that is distinct from meningioma and extracranial sarcomas. Additionally, epigenomic evaluation may provide important prognostic subtyping for this unique tumor entity.

Diagnostic Utility of TLE1 (Transducer-Like Enhancer of Split 1) in Distinguishing Synovial Sarcoma from Mimicking Tumors.

BACKGROUND: Synovial sarcoma (SS) is a high-grade spindle cell tumor that accounts for 5% to 10% of soft tissue sarcomas. The majority originate from the deep intramuscular soft tissues of extremities with common sites including knee, ankle and feet. Immunohistochemical (IHC) stain TLE1 (transducer-like enhancer of split 1) is a potent diagnostic marker for distinguishing SS from mimicking tumors. METHODOLOGY: The study was performed on 177 tumor cases, including 89 SS and 88 non-synovial sarcoma (N-SS) cases which were diagnosed at Department of Pathology and Laboratory Medicine, Aga Khan University Hospital, from July 2019 to June 2020. Hematoxylin and eosin (H&E) and IHC stained glass slides of these cases were reviewed. TLE1 expression was assessed based on the Remmele scoring system. RESULTS: Eighty-nine cases of SS and 88 cases of N-SS were included in the study. SS cases included 42 (47.2%) monophasic subtype, 6 (6.7%) biphasic subtype and 41 (46.1%) poorly differentiated subtype. Major tumor types in N-SS cases were 27 (30.7%) Ewing sarcoma (ES), 13 (14.8%) leiomyosarcoma, 10 (11.4%) undifferentiated sarcoma (US), 8 (9.1%) fibrosarcomatous dermatofibrosarcoma protuberans and 7 (8%) malignant peripheral nerve sheath tumor cases. Mean patients' age for SS cases was 26.14 years and for N-SS cases was 32.64 years. All 89 SS cases showed positive TLE1 expression. Out of 88 N-SS cases, 71 (80.7%) were TLE1 negative and 17 (19.3%) showed positive expression. CONCLUSION: This study shows that TLE1 is a very sensitive and relatively specific IHC marker for SS. TLE1 expression can be observed in other soft tissue sarcomas but diffuse strong TLE1 expression is highly specific for SS. The diagnosis should not solely rely on TLE1 expression and morphologic features but should include soft tissue specific lineage markers to avoid misdiagnosis.

Metastatic renal cell carcinoma to pancreas and gastrointestinal tract: a clinicopathological study of 3 cases and review of literature.

BACKGROUND: Renal Cell Carcinoma (RCC) metastasizes in approximately 20-30% cases. The most common sites for metastases are the lungs, bones, liver, and brain. Metastases of RCC in the gastrointestinal tract (GIT) are very rare. Metastatic RCC has a poor prognosis. We herein present a case series of three patients with metastatic disease in the colon, duodenum, and pancreas following complete resection of RCC. METHODS: Hematoxylin and Eosin and immunohistochemical slides of 3 cases of RCC metastatic to GIT were reviewed. These cases were diagnosed between 2002 and 2019 at French Medical Institute for Mothers and Children (FMIC), Kabul, Afghanistan, and Aga Khan University Hospital (AKUH), Karachi, Pakistan. We also present a detailed review of published literature. RESULTS: We reviewed cases of three patients, two females and one male, with a mean age of 57.3 years (range 40-67 years) who underwent nephrectomy for RCC. They developed metastases in the colon, pancreas, and duodenum, respectively 12-168 months (median time 156 months) following primary tumor resection. The patient with metastatic RCC in colon presented with abdominal pain and constipation. An ulcerated mass was found on colonoscopy 30 cm from the anal verge. Diagnosis of RCC with rhabdoid features was confirmed in both primary and metastatic tumors. The second patient developed a metastatic nodule in the head of pancreatic while the third patient developed metastatic nodules in the duodenum and pancreas which were detected by Computed Tomography (CT) scanning. Histopathological examination confirmed the presence of clear cell RCC in the metastatic nodules in both cases. CONCLUSION: Metastatic RCC should be considered in the differential diagnosis of mass in the gastrointestinal (including pancreaticobiliary) tract especially in presence of a past history of RCC. These patients should be screened thoroughly by physical examination and appropriate imaging studies.

Low-grade fibromyxoid sarcoma of the parapharyngeal space: an unusual location.

Low-grade fibromyxoid sarcoma (LGFMS) is an uncommon soft-tissue malignancy. LGFMS preferentially affects trunks and extremities of young adults; however, occasional cases have been reported in different sites of head and neck region including oral cavity, larynx and oropharynx. LGFMS usually exhibit areas of collagenised and myxoid stroma with appearance of spindle cells in whorling pattern. It is a challenge to diagnose it accurately as most of the time it is misdiagnosed as benign neoplastic entity of spindle cells. There have been only few isolated cases of LGFMS reported in head and neck region and LGFMS originating from the parapharyngeal space has never been reported before. We recently experienced a case of low grade fibomyxoid sarcoma in parapharyngeal space of neck. LGFMS have the propensity to locally recur and to metastasise. Due to its rarity in head and neck region, there are no well-established treatment and follow-up guidelines.

Intracranial mesenchymal tumor with FET-CREB fusion-A unifying diagnosis for the spectrum of intracranial myxoid mesenchymal tumors and angiomatoid fibrous histiocytoma-like neoplasms.

Intracranial mesenchymal tumors with FET-CREB fusions are a recently described group of neoplasms in children and young adults characterized by fusion of a FET family gene (usually EWSR1, but rarely FUS) to a CREB family transcription factor (ATF1, CREB1, or CREM), and have been variously termed intracranial angiomatoid fibrous histiocytoma or intracranial myxoid mesenchymal tumor. The clinical outcomes, histologic features, and genomic landscape are not well defined. Here, we studied 20 patients with intracranial mesenchymal tumors proven to harbor FET-CREB fusion by next-generation sequencing (NGS). The 16 female and four male patients had a median age of 14 years (range 4-70). Tumors were uniformly extra-axial or intraventricular and located at the cerebral convexities (n = 7), falx (2), lateral ventricles (4), tentorium (2), cerebellopontine angle (4), and spinal cord (1). NGS demonstrated that eight tumors harbored EWSR1-ATF1 fusion, seven had EWSR1-CREB1, four had EWSR1-CREM, and one had FUS-CREM. Tumors were uniformly well circumscribed and typically contrast enhancing with solid and cystic growth. Tumors with EWSR1-CREB1 fusions more often featured stellate/spindle cell morphology, mucin-rich stroma, and hemangioma-like vasculature compared to tumors with EWSR1-ATF1 fusions that most often featured sheets of epithelioid cells with mucin-poor collagenous stroma. These tumors demonstrated polyphenotypic immunoprofiles with frequent positivity for desmin, EMA, CD99, MUC4, and synaptophysin, but absence of SSTR2A, myogenin, and HMB45 expression. There was a propensity for local recurrence with a median progression-free survival of 12 months and a median overall survival of greater than 60 months, with three patients succumbing to disease (all with EWSR1-ATF1 fusions). In combination with prior case series, this study provides further insight into intracranial mesenchymal tumors with FET-CREB fusion, which represent a distinct group of CNS tumors encompassing both intracranial myxoid mesenchymal tumor and angiomatoid fibrous histiocytoma-like neoplasms.

Histomorphometric Analysis of Pre- and Post-Denosumab-Treated Giant Cell Tumor of Bone.

Context. Denosumab is a monoclonal antibody against RANK ligand. Its administration in giant cell tumor of bone (GCTB) cases results in elimination of giant cells and new bone formation. Neoplastic stromal cells of GCTB harbor mutation of histone 3.3 and have pre-osteoblastic properties and thus express SATB2. Objectives. To (1) analyze histological changes in post-denosumab-treated GCTB, (2) analyze expression of H3.3G34W and SATB2 in pre- and post-denosumab-treated samples, and (3) to discuss why changes occur in the expression of not only H3.3G34W but also SATB2. Materials and Methods. Hematoxylin and eosin slides of 19 cases of denosumab-treated GCTB were reviewed. Immunohistochemical stains H3.3G34W and SATB2 were performed. The number of positive mononuclear cells were counted and graded. Results. Complete absence of osteoclast-like giant cells (OCLGCs) was noted in most cases along with a fibro-osseous component merging with peripheral shell of reactive bone. Irregular trabeculae of woven bone and osteoid with focal osteoblastic rimming was seen. Spindle cells were arranged predominantly in fascicular pattern. Morphometric analysis of H3.3G34W showed a mean of 68.8% positive stromal cells in pretreatment and a mean of 26.9% positive stromal cells in posttreated specimens with a statistically significant P value (.001). Mean percentage of SATB2-positive stromal cells in the pre- and posttreatment specimens was 36.46% and 20.8%, respectively. Conclusions. Our study validates that denosumab treatment results in marked reduction of OCLGCs with increased osteoblastic activity. Decreased expression of H3.3G34W in posttreatment may be a result of decreased antigenicity of neoplastic mononuclear cells. No significant change in SATB2 expression was noted.

Malignant peripheral nerve sheath tumour of thyroid: a diagnostic dilemma.

Malignant peripheral nerve sheath tumours of thyroid are rare entities that can present a diagnostic dilemma. We present the case of a patient who presented with neck mass with a history of multiple neck surgeries and airway compression. The patient's previous histopathology was mistaken for Riedel's thyroiditis in an outside hospital, which delayed appropriate treatment leading to suffering on part of the patient and frustration on part of the physician. We emphasise that rare malignancies should be considered in rapidly growing neck masses that are causing airway compression, and histopathology of such tumours should be reported by expert pathologists.

Anal extraskeletal osteosarcoma in a man: a case report and review of the literature.

BACKGROUND: Osteosarcoma is a common malignancy of bone that usually occurs in individuals in the age range of 0-24 years. Extraskeletal osteosarcoma is a rare tumor presentation which originates in non-bony tissues. Extraskeletal osteosarcoma comprises 2-5% of all osteosarcomas and less than 1% of all soft tissue sarcomas. As compared to bone-derived osteosarcoma, extraskeletal osteosarcoma occurs in older age groups. Extraskeletal osteosarcoma has a poorer prognosis than bone osteosarcoma. To the best of our knowledge, this is the first case of extraskeletal osteosarcoma in the anal region. CASE PRESENTATION: A 70-year-old Hazara man presented to a private hospital with the chief complaints of constipation, bloody defecation, and pain during defecation of 1.5 months' duration. His past history was unremarkable. A digital rectal examination showed a solid growth in the middle part of his anus. A colonoscopic examination was done and showed a solid mass in his anal region. A computed tomography scan revealed an irregular mural thickening in the anal canal with heterogeneous enhancement. The maximum length of the involved segment was measured to be 4.5 cm. No suspicious lesions were noted in other organs. An abdominoperineal resection was performed on our patient. A 22 cm in length resected segment of his colon, consisting of the lower sigmoid, rectum, and anus was sent to us for histopathological examination. Gross examination revealed a polypoid dark-gray tumor measuring 5 × 3 × 2 cm. The cut section revealed gray and white appearance with firm-to-hard consistency and foci of ossification. Microscopic examination revealed normal anorectal mucosa and a spindle cell malignant neoplasm with osteoid formations. No evidence of epithelial carcinoma was noted. Immunohistochemical stains were positive for stabilin-2 and negative for cytokeratin, which confirmed the diagnosis of osteosarcoma. CONCLUSION: Extraskeletal osteosarcoma of the colon is rare and presence of the tumor in the rectum and anal region is extremely rare. Radiology, colonoscopy, and histopathology with immunostaining are required for the diagnosis. The accurate diagnosis of extraskeletal osteosarcoma is important as it has a different regimen of treatment with poorer prognosis compared to primary osteosarcoma of the bone.

Synchronous Well-differentiated Endometrioid Adenocarcinoma and Leiomyosarcoma of the Uterus With Pulmonary Metastasis in a 50-Yr-Old Woman: A Case Report and Review of Literature.

The most common synchronous gynecologic malignancies are endometrial and ovarian cancers. However, synchronous endometrial adenocarcinoma and uterine leiomyosarcoma are extremely rare. We report the case of a 50-yr-old woman who was diagnosed with concomitant endometrial adenocarcinoma and uterine leiomyosarcoma. The sarcomatous neoplasm was positive for anti-smooth muscle actin and CD10, and focally positive for Cytokeratin AE1/AE3 and Cytokeratin Cam 5.2. She underwent total abdominal hysterectomy with bilateral salpingoopherectomy followed by radiation, brachytherapy, and chemotherapy. Three years later, she presented with cough and dyspnea and was found to have pulmonary metastasis. These tumor cells were positive for anti-smooth muscle actin, Cytokeratin AE1/AE3, Cytokeratin Cam 5.2, and epithelial membrane antigen, and therefore a diagnosis of lung metastasis from myometrial leiomyosarcoma was made. She received chemotherapy postoperatively. Currently, the patient has multiple lung metastases, is on Megestrol Acetate and is clinically well. This is the first reported case of concomitant uterine malignancies with pulmonary metastases and a long follow-up of 9 yr. It is important to rule out carcinosarcoma as a differential diagnosis in such patients.

Atypical lipomatous tumour/well-differentiated liposarcoma and de-differentiated liposarcoma in patients aged ≤ 40 years: a study of 116 patients.

AIMS: Limited data exist on atypical lipomatous tumour (ALT)/well-differentiated liposarcoma (WDL) and de-differentiated liposarcoma (DDLPS) in children and young adults. METHODS AND RESULTS: Cases of ALT/WDL/DDLPS arising in patients aged ≤ 40 years were collected from multiple institutional and consultation archives. A total of 116 cases of ALT/WDL (75) and DDLPS (41) were identified, representing fewer than 5% of these tumours seen at our institutions during this time-period. The patients (59 male/57 female) ranged in age from 8 to 40 years. Sites included deep central (abdomen/retroperitoneum/pelvis/groin) (n = 60), extremity (n = 42), trunk (n = 5), head/neck (n = 8) and mediastinum (n = 1). De-differentiated patterns included: high-grade pleomorphic sarcoma, myxofibrosarcoma-like, heterologous rhabdomyoblastic differentiation, low-grade spindle cell sarcoma and homologous lipoblastic differentiation. Forty-one patients experienced a local recurrence and 11 patients with DDLPS developed metastasis. ALT arising in the extremities had lower recurrence rates than deep central WDL (5-year recurrence-free survival 88.9% versus 59.0%; P = 0.002), while patients with deep central DDLPS experienced significantly more adverse events compared to WDL at this site (5-year event-free survival 11.9% versus 59.0%) (P < 0.0001). Seven (of eight) head/neck tumours had follow-up available; five recurred, and one patient (DDLPS) with recurrence also experienced a metastasis. The single mediastinal tumour (DDLPS) recurred and metastasised. CONCLUSION: ALT/WDL and DDLPS occurring in patients aged ≤ 40 years is rare, but exhibits similar morphological features to its counterparts in older adults, including potential for heterologous and homologous de-differentiation in the latter. Although case numbers are limited, tumours arising in the head and neck exhibit high rates of adverse events, suggesting that classification as WDL rather than ALT is more appropriate.

Ossifying fibromyxoid tumor: a rare case.

Ossifying fibromyxoid tumour (OFMT) is a rarely occurring soft tissue neoplasm of mesenchymal origin. It is a rarely found tumour with intermediate behaviour and differentiation. Although it is mostly benign, malignant variants also exist. We are presenting a case of 32-year-old man presented in clinic with complaints of painless swelling in left distal thigh. After reviewing his X-ray, a diagnostic biopsy was planned which came out to be suspicious of solitary fibrous tumour. Other radiological workup was done and the patient was planned to undergo wide margin excision. The final histopathology showed a diagnosis of OFMT of soft tissue, atypical variant. The patient is under follow-up and is disease free. This type of tumour possesses potential of local recurrence and metastases; therefore, it is important to keep a long-term follow-up of patient.