Orbital masses as a rare presentation of Rosai-Dorfman disease: Clinicopathologic characterization of five cases.

Rosai-Dorfman disease (RDD) is a rare, non-Langerhans cell histiocytosis. Most cases present with marked, non-tender lymphadenopathy due to the proliferation of atypical histiocytes. A minority of cases involves extranodal sites and can present as bone lesions, skin rashes, pulmonary nodules, and rarely orbital masses. Orbital involvement in RDD is rare and may infrequently present as an isolated tumor mass without lymphadenopathy. This study aims to better characterize this uncommon presentation of this rare disease. Five cases of orbital RDD were identified from the last 18 years and the clinical characteristics of each case were compared with histopathological findings. Three men and two women ages 12-36 presented with complaints of eye swelling and/or vision changes. One patient had a history of neurofibromatosis type I and inflammatory pseudotumors while the other four had no signs of systemic disease or other sites of extranodal involvement at the time of presentation. Masses ranged in size from 1.0 cm to 3.5 cm and primarily involved the superior orbit. Resected lesions all displayed characteristic findings of admixed atypical histiocytes, lymphocytes, and plasma cells with a fibrotic background. Emperipolesis was seen in all cases. Immunostaining for S100 and CD68 was diffusely positive in the histiocyte population. Clinical follow-up was obtained for 4 of 5 patients: all four were disease-free at 1 to 15 years after resection. RDD should be considered in the differential for patients with orbital masses, even in the absence of lymphadenopathy or signs of systemic disease.

Polypoid Kaposi Sarcoma Involving the Lower Gastrointestinal Tract: Clinicopathologic Study of 15 Cases.

CONTEXT.­: Gastrointestinal manifestations of Kaposi sarcoma are rare but may cause morbidity. Lower gastrointestinal involvement is particularly rare and lesions may resemble conventional bowel polyps. OBJECTIVE.­: To study 15 patients who presented with lower gastrointestinal tract Kaposi sarcoma with polypoid architecture. DESIGN.­: The surgical pathology files of the departments of pathology at multiple institutions were searched for cases of Kaposi sarcoma forming polyps in the lower gastrointestinal tract (jejunum, colon, rectum); 15 cases with such features were identified. Clinicopathologic information was extracted from the medical record and documented by reviewing individual hematoxylin-eosin stained slides. RESULTS.­: The patients were 13 men and 2 women aged 26-80 years (median = 44 years). Gastrointestinal tract involvement was multifocal in 11 cases and unifocal in 4. The tumors involved the rectum, recto-sigmoid junction, cecum, ascending colon, transverse colon, and descending colon and presented as polypoid lesions measuring 0.2-2.1 cm. Six patients had upper gastrointestinal tract involvement in addition to lower gastrointestinal lesions. Histologically the tumors were characterized in 6 cases by a dense spindle cell proliferation in the lamina propria; however, the remaining cases showed only a subtle fascicular spindle cell proliferation in the lamina propria that did not form an expansile mass. CONCLUSIONS.­: Biopsies of gastrointestinal polyps showing absence of the common features of hyperplastic or adenomatous polyps, particularly in immunocompromised patients, should be carefully examined for the presence of a stromal spindle cell proliferation. Use of immunohistochemical stains, particularly human herpesvirus-8, can help in establishing the correct diagnosis.

Nodular Fasciitis of the Buccal Mucosa with a Novel USP6 Gene Rearrangement: A Case Report and Review of the Literature.

Nodular fasciitis is a rare but benign fibroblastic proliferation that typically presents as a solitary lesion with rapid growth and variable mitotic activity. The lesions usually occur on the extremities and occasionally in the head/neck region. Involvement of the buccal mucosa is extremely rare with only few reports in the literature; in this case report, we describe a 41 year old female who presented with a 6-month history of a stable intraoral lump at the junction of the upper and lower lip. Fine needle aspiration revealed an atypical spindle cell population with plump cells. The surgical excision demonstrated a well circumscribed tan-white firm nodule. Histologic examination revealed a spindle cell proliferation that grew in short, intersecting fascicles with focal storiform architecture. The lesion had a pushing border that was not overtly infiltrative and the stroma contained focal myxoid changes giving a "tissue culture" appearance to the cells. Immunohistochemical testing showed the tumor cells were vimentin (+), SMA (+), weakly Calponin (+), and desmin (-), cytokeratin (-), AE1/AE3 (-), S100 (-), ALK (-), STAT6 (-), and beta-catenin (-). Fluorescence in-situ hybridization (FISH) revealed a USP6 gene rearrangement with an atypical probe pattern. Next generation sequencing identified a novel SPTAN1::USP6 fusion gene confirming the diagnosis of buccal nodular fasciitis. Identification of the characteristic histologic features and USP6 gene rearrangements helped support the diagnosis. A review of the literature identified 25 cases of nodular fasciitis involving the buccal mucosa. The occurrence of this tumor in an unusual location may pose difficulties for diagnosis.

Inflammatory Giant Cell Carcinoma of the Lung: Clinicopathologic, Immunohistochemical, and Next-generation Sequencing Study of 14 Cases.

A distinctive histological variant of poorly differentiated, sarcomatoid, non-small cell lung carcinoma characterized by a discohesive population of giant tumor cells associated with prominent interstitial inflammatory cell infiltrates is described. The tumors occurred in 7 women and 7 men, 42 to 72 years of age (mean: 56 y). They predominantly affected the upper lobes and measured 1.3 to 9 cm in greatest diameter (mean: 4.6 cm). The tumor cells were characterized by large pleomorphic nuclei with prominent nucleoli, ample cytoplasm, and frequent abnormal mitoses, and were surrounded by a dense inflammatory cell infiltrate, often associated with emperipolesis. Immunohistochemical stains were positive in the tumor cells for cytokeratin AE1/AE3 and CK8/18 and negative for TTF1, napsin A, p40, and CK5/6. Next-generation sequencing was performed in all cases using the Oncomine Precision Assay; the most common abnormalities found included TP53 mutations (9 cases) and AKT1 amplification (8 cases), followed by KRAS mutations (4 cases) and MAP2K1/2 mutations (4 cases). Clinical follow-up was available in 13 patients. Three patients presented with metastases as the initial manifestation of disease; 8 patients died of their tumors from 6 months to 8 years (mean: 2.7 y); 3 patients were alive and well from 4 to 6 years; and 2 patients had metastases when last seen but were lost to follow-up thereafter. The importance of recognizing this distinctive and aggressive variant of non-small cell lung carcinoma lies in avoiding confusion with a sarcoma or other types of malignancy.

Insulinoma-Associated Protein-1 Expression in Lymphoepithelial Carcinoma of the Thymus: A Potential Pitfall for Diagnosis With Neuroendocrine Carcinomas of the Thymus.

CONTEXT.­: Insulinoma-associated protein-1 (INSM1) is a recently developed immunohistochemical marker claimed to be highly specific and sensitive for the diagnosis of neuroendocrine malignancies. Recent studies, however, have demonstrated that this marker can also be expressed in non-neuroendocrine neoplasms including squamous cell carcinoma of the thymus. OBJECTIVE.­: To examine INSM1 expression in lymphoepithelial thymic carcinomas. DESIGN.­: Thirty-four cases of lymphoepithelial carcinoma of the thymus were examined by immunohistochemistry or in situ hybridization for INSM1, synaptophysin, chromogranin, CD5, CD117, Epstein-Barr virus-encoded small ribonucleic acid (EBER), and Ki-67. Basic clinical information was abstracted from the medical record. RESULTS.­: The patients were 14 women and 20 men, aged 20 to 85 years. The tumors arose in the anterior mediastinum without any previous history or evidence of malignancy at other sites. Immunohistochemical staining showed moderate to strong positivity of the tumor cells for INSM1 in 65% of cases (22 of 34), focal weak positivity in 20% (7 of 34), and negative staining in 5 cases. Chromogranin staining was focally and weakly positive in 1 case, and synaptophysin showed only focal weak positivity in scattered tumor cells in 12 cases. No significant correlation could be identified between the pattern and intensity of staining for INSM1 and staining for CD5, CD117, and Ki-67. CONCLUSIONS.­: INSM1 positivity in lymphoepithelial carcinoma of the thymus may represent a pitfall for diagnosis, particularly in small biopsy samples. Awareness of this finding may be of importance to avoid misdiagnosis of neuroendocrine malignancy.

Outcome of Primary Lung Salivary Gland-Type Carcinoma: A Population-Based Study.

Introduction. Primary pulmonary salivary gland-type carcinomas are rare malignancies arising from minor salivary gland tissue in the lower respiratory tract. Given their rarity, constituting <1% of all primary lung malignancies, their epidemiological features and outcomes remain poorly documented. This study analyzed data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database to identify primary pulmonary salivary gland carcinomas, including the most prevalent tumor types. Methods. All patients diagnosed with mucoepidermoid carcinoma, adenoid cystic carcinoma, and epithelial-myoepithelial carcinoma, with the lung designated as the primary site between 1975 and 2019, were subject to analysis. Overall and disease-specific survival were calculated using Kaplan-Meier curves and Cox proportional hazards models. Results. The study identified 323 mucoepidermoid carcinoma, 284 adenoid cystic carcinoma, and 6 epithelial-myoepithelial carcinoma diagnosed as pulmonary salivary gland-type carcinoma. An analysis of age distribution revealed a unimodal pattern for both mucoepidermoid carcinoma and adenoid cystic carcinoma, with most patients diagnosed after age 40. Most patients were Caucasians (77% for mucoepidermoid carcinoma and 83% for adenoid cystic carcinoma). Both disease-specific and overall survival were worse for patients diagnosed at the age of 60 years or above. Race or sex did not significantly impact patient survival. High-grade mucoepidermoid carcinoma demonstrated a significantly worse prognosis than low or intermediate-grade mucoepidermoid carcinoma. Conclusion. A comprehensive review of clinical and epidemiological features of pulmonary salivary gland-type carcinomas reveals that the age of diagnosis and tumor grade are the most significant factors in determining patient survival.

Pseudosquamous Adenocarcinoma of the Lung: Clinicopathologic and Immunohistochemical Study of 10 Cases.

Pseudosquamous adenocarcinoma of the lung is an unusual morphologic variant of poorly differentiated non-small cell lung carcinoma that superficially resembles a squamous cell carcinoma. We have examined 10 cases of these tumors in 4 women and 6 men, aged 47 to 93 years. The tumors were all peripheral and measured from 1.5 to 5.5 cm. All cases were characterized by solid nests of large polygonal tumor cells containing atypical nuclei with abundant cytoplasm and sharp cell borders, adopting a pavement-like architecture that simulated squamous cell carcinoma. Some cases demonstrated intracytoplasmic hyaline inclusions suggestive of keratinization. The nests of tumor cells often showed central comedo-like areas of necrosis. Intercellular bridges were not seen in any of the cases. The tumors often displayed marked clearing of the cytoplasm enhancing their epidermoid appearance. In 4 cases, the solid pseudosquamous areas were seen to merge with a focal lepidic adenocarcinoma component, and in 1 case, abortive microscopic foci of acinar differentiation were also noted within the tumor. One case showed focal sarcomatoid spindle cell areas. The tumor cells were negative for p40 and CK5/6 and labeled with TTF1 or Napsin-A, confirming an adenocarcinoma phenotype. Clinical follow-up information was available in 8 patients; 6 patients died of their tumors between 6 months to 11 years after diagnosis (mean: 3.1 y). One patient died of complications related to surgery and one patient with a low-stage tumor died at 27 years from other causes. Solid pattern adenocarcinomas can be confused for squamous cell carcinoma and may require immunohistochemistry to determine their true phenotype.

Non-small cell lung carcinoma with clear cell features: a clinicopathologic, immunohistochemical, and molecular study of 31 cases.

Non-small cell lung carcinoma with predominantly clear cell features is a rare histologic presentation of lung carcinoma. We have examined 31 cases of lung carcinomas showing extensive clear cell features. The patients were 10 women and 21 men aged 47-92 years (mean: 70 years). The tumors showed a predilection for the right upper and lower lobes and measured from 0.8 to 9.5 cm (mean: 4.2 cm). By immunohistochemistry, 9 cases were typed as adenocarcinoma, 19 cases as squamous cell carcinoma, and 3 showed a "null" phenotype with complete loss of markers for adenocarcinoma or squamous cell carcinoma. Most cases that typed as adenocarcinoma showed a solid growth pattern. A subset of the solid adenocarcinoma cases showed a distinctive "pseudosquamous" morphology. Next-generation sequencing was performed in 20 cases and showed a variety of molecular alterations. The most common abnormalities were found in the TP53 gene (9 cases), FGFR gene family (8 cases), KRAS (5 cases), AKT1 (5 cases), and BRAF (3 cases). Clinical follow-up was available in 21 patients; 16/21 patients died of their tumors from 6 months to 12 years after initial diagnosis (mean: 4.2 years, median: 1.5 years). Four patients were alive and well from 4 to 27 years (mean: 11.5 years, median: 7.5 years); all were pathologic stage 1 or 2. NSCLC with clear cell features can display aggressive behavior and needs to be distinguished from various other tumors of the lung that can show clear cell morphology. The identification of targetable molecular alterations in some of these tumors may be of value for therapeutic management.

Maackia amurensis seed lectin (MASL) and soluble human podoplanin (shPDPN) sequence analysis and effects on human oral squamous cell carcinoma (OSCC) cell migration and viability.

Maackia amurensis lectins serve as research and botanical agents that bind to sialic residues on proteins. For example, M. amurensis seed lectin (MASL) targets the sialic acid modified podoplanin (PDPN) receptor to suppress arthritic chondrocyte inflammation, and inhibit tumor cell growth and motility. However, M. amurensis lectin nomenclature and composition are not clearly defined. Here, we sought to definitively characterize MASL and its effects on tumor cell behavior. We utilized SDS-PAGE and LC-MS/MS to find that M. amurensis lectins can be divided into two groups. MASL is a member of one group which is composed of subunits that form dimers, evidently mediated by a cysteine residue in the carboxy region of the protein. In contrast to MASL, members of the other group do not dimerize under nonreducing conditions. These data also indicate that MASL is composed of 4 isoforms with an identical amino acid sequence, but unique glycosylation sites. We also produced a novel recombinant soluble human PDPN receptor (shPDPN) with 17 threonine residues glycosylated with sialic acid moieties with potential to act as a ligand trap that inhibits OSCC cell growth and motility. In addition, we report here that MASL targets PDPN with very strong binding kinetics in the nanomolar range. Moreover, we confirm that MASL can inhibit the growth and motility of human oral squamous cell carcinoma (OSCC) cells that express the PDPN receptor. Taken together, these data characterize M. amurensis lectins into two major groups based on their intrinsic properties, clarify the composition of MASL and its subunit isoform sequence and glycosylation sites, define sialic acid modifications on the PDPN receptor and its ability to act as a ligand trap, quantitate MASL binding to PDPN with KD in the nanomolar range, and verify the ability of MASL to serve as a potential anticancer agent.

CHRNA6 RNA In Situ Hybridization Is a Useful Tool for the Diagnosis of Extraskeletal Myxoid Chondrosarcoma.

Extraskeletal myxoid chondrosarcoma (EMC) is an uncommon mesenchymal neoplasm characteristically composed of uniform-appearing round to spindle-shaped cells with eosinophilic cytoplasm and abundant myxoid extracellular matrix. Although the majority of cases harbor a pathognomonic t(9;22) translocation that fuses EWSR1 with the orphan nuclear receptor NR4A3, there are less common variants that partner NR4A3 with TAF15, TCF12, or TFG. By immunohistochemistry, EMC has features of both cartilaginous and neuroendocrine differentiation, as evidenced by inconsistent expression of S100 protein and synaptophysin or INSM1, respectively, in a subset of cases. Given the limitations of available immunohistochemical stains for the diagnosis of EMC, we analyzed genome-wide gene expression microarray data to identify candidate biomarkers based on differential expression in EMC in comparison with other mesenchymal neoplasms. This analysis pointed to CHRNA6 as the gene with the highest relative expression in EMC (96-fold; P = 8.2 × 10-26) and the only gene with >50-fold increased expression in EMC compared with other tumors. Using RNA chromogenic in situ hybridization, we observed strong and diffuse expression of CHRNA6 in 25 cases of EMC, including both EWSR1-rearranged and TAF15-rearranged variants. All examined cases of histologic mimics were negative for CHRNA6 overexpression; however, limited CHRNA6 expression, not reaching a threshold of >5 puncta or 1 aggregate of chromogen in >25% of cells, was observed in 69 of 685 mimics (10.1%), spanning an array of mesenchymal tumors. Taken together, these findings suggest that, with careful interpretation and the use of appropriate thresholds, CHRNA6 RNA chromogenic in situ hybridization is a potentially useful ancillary histologic tool for the diagnosis of EMC.

Selected Case From the Arkadi M. Rywlin International Pathology Slide Seminar: Involvement of Skin and Soft Tissue by Erdheim-Chester Disease.

Erdheim-Chester disease is a rare form of non-Langerhans cell histiocytosis that preferentially involves long bones but can affect a variety of other organs. Initial presentation with extraskeletal involvement is not unusual and is most commonly observed in the central nervous system, heart, retroperitoneum, lungs, and skin. Initial presentation of the disease as a subcutaneous soft tissue mass is exceedingly rare and may pose difficulties for diagnosis. We describe a case of Erdheim-Chester disease that initially presented as a cutaneous and subcutaneous soft tissue mass in the right posterior shoulder of a 52-year-old man.

Sclerosing epithelioid fibrosarcoma of bone with hybrid features: clinicopathologic, radiologic, and molecular analysis of three cases.

Sclerosing epithelioid fibrosarcoma (SEF) occurring as a primary bone tumor is exceptionally uncommon. Even more rare are cases of SEF that show morphologic overlap with low-grade fibromyxoid sarcoma (LGFMS). Such hybrid lesions arising within the bone have only rarely been reported in the literature. Due to their variegated histomorphology and non-specific radiologic features, these tumors may pose diagnostic difficulties. Herein we describe three molecularly confirmed primary bone cases of sclerosing epithelioid fibrosarcoma that demonstrated prominent areas showing the features of LGFMS and with areas resembling so-called hyalinizing spindle cell tumor with giant rosettes (HSCTGR). Two patients were female and one was male aged 26, 47, and 16, respectively. The tumors occurred in the femoral head, clavicle, and temporal bone. Imaging studies demonstrated relatively well-circumscribed radiolucent bone lesions with enhancement on MRI. Cortical breakthrough and soft tissue extension were present in one case. Histologically the tumors all demonstrated hyalinized areas with SEF-like morphology as well as spindled and myxoid areas with LGFMS-like morphology. Two cases demonstrated focal areas with rosette-like architecture as seen in HSCTGR. The tumors were all positive for MUC4 by immunohistochemistry and cytogenetics, fluorescence in-situ hybridization, and next-generation sequencing studies identified EWSR1 gene rearrangements confirming the diagnosis in all three cases.Hybrid SEF is exceedingly rare as a primary bone tumor and can be difficult to distinguish from other low-grade spindled and epithelioid lesions of bone. MUC4 positivity and identification of underlying EWSR1 gene rearrangements help support this diagnosis and exclude other tumor types.

Molecular pathology as basis for timely cancer diagnosis and therapy.

Precision and personalized therapeutics have witnessed significant advancements in technology, revolutionizing the capabilities of laboratories to generate vast amounts of genetic data. Coupled with computational resources for analysis and interpretation, and integrated with various other types of data, including genomic data, electronic medical health (EMH) data, and clinical knowledge, these advancements support optimized health decisions. Among these technologies, next-generation sequencing (NGS) stands out as a transformative tool in the field of cancer treatment, playing a crucial role in precision oncology. NGS-based workflows are employed across a range of applications, including gene panels, exome sequencing, and whole-genome sequencing, supporting comprehensive analysis of the entire cancer genome, including mutations, copy number variations, gene expression profiles, and epigenetic modifications. By utilizing the power of NGS, these workflows contribute to enhancing our understanding of disease mechanisms, diagnosis confirmation, identifying therapeutic targets, and guiding personalized treatment decisions. This manuscript explores the diverse applications of NGS in cancer treatment, highlighting its significance in guiding diagnosis and treatment decisions, identifying therapeutic targets, monitoring disease progression, and improving patient outcomes.

Clinicopathologic features, tumor immune microenvironment and genomic landscape of EBV-related and EBV-unrelated poorly differentiated nonkeratinizing squamous cell carcinoma of the thymus.

OBJECTIVES: Knowledge regarding thymic EBV-related poorly differentiated nonkeratinizing squamous cell carcinoma (PDNKSCC), also known as lymphoepithelial carcinoma (LEC), is extremely limited due to its rarity. MATERIALS AND METHODS: This multi-institutional study enrolled 85 patients with thymic PDNKSCC. DNA in situ hybridization was performed to evaluate the EBV status of all 85 cases. Immunohistochemistry and next generation sequencing were performed to compare the differences in the clinicopathological and molecular features between EBV-related and EBV-unrelated PDNKSCC. Tumor-infiltrating lymphocytes (TILs) were also analyzed by these methods. RESULTS: The 85 cases were classified into 27 EBV-related PDNKSCCs (31.8 %) and 58 EBV-unrelated PDNKSCCs (68.2 %) according to the EBV status, and 35 Lymphoepithelioma pattern (LP) (41.2 %) and 50 desmoplastic pattern (DP) (58.8 %) according to the histological characteristics. Compared to the EBV-unrelated PDNKSCC, EBV-related PDNKSCC showed a younger patient predominance and more commonly displayed a LP subtype. Additionally, LP-type cases were divided into two groups: Group 1 (EBV-related, 20/85) and Group 2 (EBV-unrelated, 15/85); the DP-type cases were divided into Group 3 (EBV-unrelated, 43/85) and Group 4 (EBV-related, 7/85). The four Groups showed a significant association with patients' OS and PFS. EBV-related PDNKSCC had significantly higher PD-L1 + tumor cells (TCs) and PD-L1 + and CD8 + immune cells (ICs) than EBV-unrelated PDNKSCC. The tumor microenvironment immune type (TMIT) I (PDL1-Tumor+/CD8-High) was more common in EBV-related PDNKSCC, especially in Group 1(LP and EBV related) with more than 90 % cases belonged to TMIT I. Molecular analysis demonstrated that EBV-related PDNKSCC had a significantly higher tumour mutational burden and frequency of somatic mutations than EBV-unrelated cases. CONCLUSIONS: EBV-related PDNKSCC, especially the Group 1, could be a candidate for immunotherapy and EBV positivity may provide an indication for the selection of targeted therapy due to their high tumour mutational burden.

Calcified Chondroid Mesenchymal Neoplasm: Exploring the Morphologic and Clinical Features of an Emergent Entity With a Series of 33 Cases.

Calcified chondroid mesenchymal neoplasm is a term proposed for tumors with a spectrum of morphologic features, including cartilage/chondroid matrix formation, that frequently harbor FN1 gene fusions. We report a series of 33 cases of putative calcified chondroid mesenchymal neoplasms, mostly referred for expert consultation out of concern for malignancy. Patients included 17 males and 16 females, with a mean age of 51.3 years. Anatomic locations include the hands and fingers, feet and toes, head and neck, and temporomandibular joint; 1 patient presented with multifocal disease. Radiologic review showed soft tissue masses with variable internal calcification, which occasionally scalloped bone but in all cases appeared indolent/benign. Tumors had a mean gross size of 2.1 cm and a homogenous rubbery to fibrous/gritty tan-white cut surface. Histology demonstrated multinodular architecture with a prominent chondroid matrix and increased cellularity towards the periphery of the nodules. The tumor cells were polygonal with eccentric nuclei and bland cytologic features and showed a variable amount of increased spindled / fibroblastic forms in the perinodular septa. The majority of cases had notable grungy and/or lacy calcifications. A subset of cases demonstrated at least focal areas of increased cellularity and osteoclast-like giant cells. Herein, we confirm the distinct morphologic and clinicopathologic features associated with this entity with the largest series to date, with a focus on practical diagnostic separation from similar chondroid neoplasms. Awareness of these features is critical in avoiding pitfalls, including a malignant diagnosis of chondrosarcoma.

Pleomorphic Rhabdomyosarcoma: A Systematic Review with Outcome Analysis and Report of a Rare Abdominal Wall Lesion.

Introduction. Pleomorphic rhabdomyosarcoma (RMS) is an aggressive and rare malignant neoplasm with a poor prognosis. As its name suggests, this tumor exhibits extensive pleomorphism with features of skeletal muscle differentiation. Due to its rarity, its diagnosis is often a clinical and pathological challenge. Since only small case series and a few scattered case reports exist in the literature, the impact of different demographic features, tumor site, and/or treatment modality on patient outcomes has yet to be extensively studied. Methods. We report a case of a pleomorphic RMS presenting atypically as an abdominal wall mass. We have also analyzed the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) database to determine the factors affecting the outcome of this neoplasm. Moreover, we present a review and summary of pleomorphic RMS cases arising from the abdominal wall reported in the English language literature. Results. We found two hundred and forty-two cases of pleomorphic RMS in the SEER database. The majority of the patients were diagnosed after the age of 40, with the age of diagnosis showing a unimodal distribution. The majority of the patients were Caucasian (82%) and male (59%). Age of diagnosis, tumor stage, and surgical management significantly affected the patients' outcome, while patients' ethnicity, sex, or tumor site did not affect the outcome. We only found five previously reported cases of pleomorphic RMS arising from the abdominal wall. Conclusions. Pleomorphic RMS arising from the abdominal wall is extremely rare. Our data sheds light on the factors affecting the outcome of pleomorphic RMS. We have also discussed the challenges involving the histopathological diagnosis of this rare neoplasm and how to best approach this task.

Epithelioid and Clear Cell Solitary Fibrous Tumors: Clinicopathologic, Immunohistochemical, and Molecular Genetic Study of 13 Cases.

Solitary fibrous tumors (SFTs) are ubiquitous soft tissue neoplasms known for their protean histology and potentially aggressive behavior. Although most cases are composed of a monotonous proliferation of spindle cells, some tumors show unusual cytologic features. We have studied 13 SFTs that were characterized by a predominant population of round epithelioid cells with abundant eosinophilic cytoplasm and clear cell changes. The tumors occurred in 8 women and 5 men, aged 36 to 80 years (mean=63 y), and were located within the orbit (3), lower extremity (3), retroperitoneum (2), abdominal cavity (2), and superficial soft tissues of the neck, pelvis, and pubis (1 each). The tumors measured from 3.5 to 24.5 cm. Using a risk assessment system, 6 cases were stratified as low-risk tumors; 3 of these showed no evidence of recurrence or metastases from 6 to 18 years, and 1 tumor in the orbit recurred and led to the patient's demise. Five cases were of intermediate risk; clinical follow-up showed no evidence of recurrence or metastases from 3 to 4 years in 3 patients, and 1 patient suffered a recurrence 4 years after diagnosis. Two cases were high risk; 1 patient died after 1 year and the second patient experienced local recurrence at 4 years. Immunohistochemical studies showed nuclear positivity for STAT6 in 10 cases. CD34 immunohistochemistry was positive in 11 cases. A NAB2::STAT6 rearrangement was present in all cases. Epithelioid and clear cell SFT should be considered in the differential diagnosis of soft tissue neoplasms with epithelioid and clear cell morphology.

Desmoplastic Adamantinoma-like Thymic Carcinoma: Clinicopathologic, Immunohistochemical, and Molecular Study of 5 Cases.

Five cases of a heretofore unreported rare variant of thymic carcinoma characterized by a striking resemblance to adamantinoma of the mandible are described. The tumors occurred in 4 women and 1 man aged 58 to 76 years (mean: 67.8 y); they arose in the anterior mediastinum and measured from 5.3 to 12.0 cm in greatest diameter (mean: 8.9 cm). Presenting symptoms included chest pain, shortness of breath, and in 2 patients, pleural effusion. One tumor was asymptomatic and discovered incidentally. Histologically, the tumors were extensively desmoplastic, and the cellular proliferation was characterized by multiple islands of squamous epithelium with striking peripheral palisading of nuclei and central areas containing clear cells resembling a stellate reticulum. Areas of preexisting spindle cell thymoma were identified in 2 cases; these areas gradually merged with the higher-grade component of the lesion. Cystic changes were noted in 3 cases. Immunohistochemical studies in 3 cases showed the tumor cells were positive for cytokeratins, p40 and p63, and all showed a high proliferation rate (>50% nuclear positivity) with Ki-67. Next-generation sequencing was performed in 2 cases that showed amplification of the AKT1 gene (copy numbers 6 and 13). Clinical follow-up in 3 patients showed recurrence and metastasis after 1 and 2 years; 1 patient passed away 2 years after diagnosis due to the tumor. Desmoplastic adamantinoma-like thymic carcinoma represents an unusual histologic variant of thymic carcinoma that needs to be distinguished from metastases from similar tumors to the mediastinum.

Atypical thymomas with squamoid and spindle cell features: clinicopathologic, immunohistochemical and molecular genetic study of 120 cases with long-term follow-up.

Thymomas are rare tumors characterized by a broad range of morphologic appearances that can sometimes give rise to difficulties for classification. We have studied a series of 120 thymoma patients in whom the tumors were characterized by sheets of atypical epithelial cells with squamoid and/or spindle cell features. They occurred in 63 men and 57 women and presented as a discrete mass in the anterior mediastinum measuring 2-23 cm (mean: 8.2 cm). Patients' ages ranged from 14 to 86 years (mean: 57.8) and most had symptoms referable to a mass lesion. 20 patients had myasthenia gravis or other autoimmune disorder. 76 cases were characterized by a predominant population of round to polygonal tumor cells while 32 cases were characterized by atypical oval or spindle cells. 12 cases showed mixed features and 16 cases showed the development of thymic carcinoma arising from thymoma. All cases were positive for p40/p63 and cytokeratin AE1/AE3. 23 cases were positive for CD5 (25%), and 13 for CD117 (14%). MIB1 showed a significant increase in proliferative activity (mean = 11.6%). Next generation sequencing in 47 cases did not disclose any variants amenable to current targeted therapies. Clinical follow up ranging from 2 to 29 years showed a progressive increase in aggressive behavior and fatality rate with advancing stage. Overall survival was 87% at 5 years, 67% at 10 years, and 23% at 20 years. Completeness of resection and staging were the most significant parameters for survival. The more aggressive tumors followed a protracted clinical course with multiple recurrences and metastases over a long period of time (mean = 19.8 years from time of initial relapse to death). Atypical thymomas are a distinct category of thymic epithelial neoplasm characterized by a slowly progressive clinical course with increased potential for metastases, transformation to a higher-grade malignancy, and fatal outcome in some cases.