Extranodal follicular dendritic cell sarcoma of the lung.

Follicular dendritic cell sarcoma (FDCS) is a rare, mesenchymal neoplasm that may be nodal or extranodal in location. Lung involvement is rare. It is a slow-growing, painless tumor with a frequent capacity to recur and metastasize. We present a case of extranodal FDCS of the lung with an unusual presentation. A 34-year-old man presented with the complaints of haemoptysis and chest pain. A large left perihilar mass with endobronchial component was found on radiological evaluation. On endobronchial biopsy and mediastinal tru-cut biopsy, differential diagnoses of an inflammatory myo-fibrohistiocytic lesion and leiomyosarcoma were provided on the basis of morphological features of bipolar spindled cells arranged in intersecting fascicles and storiform patterns and immunophenotyping. A pneumonectomy was performed for the mass on which further immunohistochemical evaluation with CD21, CD35, and D2-40 finally helped form a diagnosis of FDCS. The patient recovered well from the surgery and has been on follow-up ever since. Owing to the rarity of this condition and its non-specific clinical features, FDCS is often misdiagnosed in the absence of appropriate immunohistochemistry. An of awareness of its morphological features and immunophenotype is, thus, necessary to provide early treatment and follow-up in order to prevent its recurrence and metastasis.

Superficial CD34-Positive Fibroblastic Tumor: A Newly Recognized Entity With Overlapping Features of PRDM10-Rearranged Soft Tissue Tumors.

Superficial CD34-positive fibroblastic tumor (SCPFT) is a recently identified, infrequent, low-grade mesenchymal neoplasm, first identified in 2014. Although it is relatively new to the field, SCPFT has been gaining prominence in surgical pathology practice because of its distinctive features. As of now, there are limited reported cases of SCPFT, with fewer than 100 instances documented in scientific literature. This distinctive blend of rarity and intriguing variability in presentation emphasizes the significance of identifying and understanding this uncommon entity, facilitating precise diagnosis and optimal management. In this article, we aimed to present a notable case of SCPFT in a male in his 20s who presented with a distinct subcutaneous mass measuring 2.4 × 1.8 cm at the medial aspect of the knee joint. The patient reported no significant medical history or trauma to the affected area. MRI of the knee showed a well-defined 2.4 × 1.8 cm subcutaneous mass with no definite communication with the underlying ligament or meniscus. The histopathological examination revealed spindle cell neoplasm arranged in intersecting fascicles, accompanied by arborizing blood vessels. Neoplastic spindle cells exhibited marked nuclear pleomorphism, and abundant and eosinophilic cytoplasm, with focal areas of granular, glassy, and lipidized cytoplasm. Nuclear pseudo inclusions and a few mitotic figures (1-2 per high-power field) were noted. Inflammatory infiltrates were identified within the neoplasm, comprising eosinophils and lymphocytes, highlighting an immune response within the tumor microenvironment. The surgical margin exhibited involvement with the tumor infiltrates, with the neoplastic cells extending into the adjacent fat tissue. This finding indicates local tumor spread and potential challenges in achieving complete resection. Immunohistochemical staining showed positive staining for CD34, corroborating the diagnosis of a CD34-positive fibroblastic tumor. Focal positive staining for pan-CK was noted. Staining for CD31, smooth muscle actin (SMA), desmin, S100, and anaplastic lymphoma kinase (ALK) was negative, supporting the diagnosis. The Ki67 proliferation index was low.

The KAT6B::KANSL1 Fusion Defines a New Uterine Sarcoma With Hybrid Endometrial Stromal Tumor and Smooth Muscle Tumor Features.

Neoplasms harboring a KAT6B/A::KANSL1 fusion were initially reported as benign (leiomyomas) and malignant (leiomyosarcomas, low-grade endometrial stromal sarcomas [LG-ESSs]) uterine neoplasms. However, they may represent an emerging entity characterized by clinical aggressiveness contrasting with a rather reassuring microscopic appearance. Here, we aimed to confirm that this neoplasm is a distinct clinicopathologic and molecular sarcoma and identify criteria that should alert pathologists and lead to KAT6B/A::KANSL1 fusion testing in routine practice. Therefore, we conducted a comprehensive clinical, histopathologic, immunohistochemical, and molecular study, including array comparative genomic hybridization, whole RNA-sequencing, unsupervised clustering, and cDNA mutational profile analyses of 16 tumors with KAT6B::KANSL1 fusion from 12 patients. At presentation, patients were peri-menopausal (median, 47.5 years), and the primary tumors were located in the uterine corpus (12/12, 100%), with an additional prevesical location in 1 (8.3%) of 12 cases. The relapse rate was 33.3% (3/9). All tumors (16/16, 100%) showed morphologic and immunohistochemical features overlapping between leiomyoma and endometrial stromal tumors. A whirling recurrent architecture (resembling fibromyxoid-ESS/fibrosarcoma) was found in 13 (81.3%) of 16 tumors. All tumors (16/16, 100%) exhibited numerous arterioliform vessels, and 13 (81.3%) of 18 had large hyalinized central vessels and collagen deposits. Estrogen and progesterone receptors were expressed in 16 (100%) of 16 and 14 (87.5%) of 16 tumors, respectively. Array comparative genomic hybridization performed on 10 tumors classified these neoplasms as simple genomic sarcomas. Whole RNA-sequencing on 16 samples and clustering analysis on primary tumors found that the KAT6B::KANSL1 fusion always occurred between exons 3 of KAT6B and 11 of KANSL1; no pathogenic variant was identified on cDNA, all neoplasms clustered together, close to LG-ESS, and pathway enrichment analysis showed cell proliferation and immune infiltrate recruitment pathway involvement. These results confirm that the sarcomas harboring a KAT6B/A::KANSL1 fusion represent a distinct clinicopathologic entity, close to LG-ESS but different, with clinical aggressiveness despite a reassuring morphology, for which the KAT6B/A::KANSL1 fusion is the molecular driver alteration.

CT of retroperitoneal solitary fibrous tumor.

Solitary fibrous tumors are rare tumors of pluripotent fibroblastic or myofibroblastic origin that generally arise among older individuals, with a mean age of onset ranging from 55 to 65 years. Though typically associated with pleural involvement, solitary fibrous tumors can emerge in virtually every anatomic location within the body. Although most solitary fibrous tumors are benign, approximately 20% may exhibit malignant features such as local invasion, recurrence, and metastases. In this article, we report the case of a 58-year-old male with a diagnosis of a retroperitoneal solitary fibrous tumor. We analyze computed tomography imaging findings and additionally correlate imaging features with the patient's unique pathological and genotypic findings to optimize diagnosis.

Application of immunohistochemical studies in diagnosing emerging superficial mesenchymal neoplasms.

Molecular diagnostics, with the subsequent development of novel immunohistochemical markers, continues to advance and expand the field of soft tissue pathology. As such, the ever-evolving molecular diagnostic landscape will continue to shape and refine our understanding and classification of neoplasms. This article reviews the current literature on various tumors of mesenchymal origin, including fibroblastic/fibrohistiocytic, adipocytic, vascular, and tumors of uncertain origin. We aim to give the reader a detailed understanding and pragmatic approach to various new and established immunohistochemical stains in diagnosing these neoplasms and also discuss various pitfalls with significant repercussions.

Utility of Retrospective Molecular Analysis in Diagnostically Challenging Mesenchymal Neoplasms.

Introduction: Molecular analysis plays a growing role in the diagnosis of mesenchymal neoplasms. The aim of this study was to retrospectively apply broad, multiplex molecular assays (a solid tumor targeted next-generation sequencing [NGS]) assay and single nucleotide polymorphism [SNP] microarray) to selected tumors, exploring the current utility and limitations. Methods: We searched our database (2010-2020) for diagnostically challenging mesenchymal neoplasms. After histologic review of available slides, tissue blocks were selected for NGS, SNP microarray, or both. DNA and RNA were extracted using the AllPrep DNA/RNA FFPE Kit Protocol on the QIAcube instrument. The NGS platform used was the TruSight Tumor 170 (TST-170). For SNP array, copy number variant (CNV) analysis was performed using the OncoScanTM CNV Plus Assay. Results: DNA/RNA was successfully extracted from 50% of tumors (n = 10/20). Specimens not successfully extracted included 6 core biopsies, 3 incisional biopsies, and 1 resection; 4 were decalcified (3 hydrochloric acid, 1 ethylenediaminetetraacetic acid). Higher tumor proportion and number of tumor cells were parameters positively associated with sufficient DNA/RNA extraction whereas necrosis and decalcification were negatively associated with sufficient extraction. Molecular testing helped reach a definitive diagnosis in 50% of tumors (n = 5/10). Conclusions: Although the overall utility of this approach is limited, these molecular panels can be helpful in detecting a specific "driver" alteration.

Prophylactic oophorectomy and aromatase inhibitors for premenopausal deep angiomyxoma: A case report and literature review.

Deep angiomyxoma is a rare, infiltrative, hormone-dependent, benign-mesenchymal neoplasm that occurs in the deep soft tissues of the perineal regions. In total, 33% females with newly diagnosed deep angiomyxoma will typically relapse within 5 years after the standard treatment of radical resection. Postoperative hormone therapy is frequently administered to prevent recurrence, but the role of prophylactic oophorectomy in premenopausal women remain to be fully elucidated. In the present report, a 42-year-old Japanese woman was referred for a refractory Bartholin's cyst that is 14 cm in diameter. Based on the results of imaging (unenhanced CT and MRI) and histopathology, deep angiomyxoma was suspected, but no definitive diagnosis was possible. Tumor resection and bilateral salpingo-oophorectomy were performed before the postoperative diagnosis was confirmed to be deep angiomyxoma. The patient received an aromatase inhibitor (2.5 mg letrozole daily) as adjuvant hormonal therapy. There was no evidence of recurrence at the 1-year postoperative follow-up. In conclusion, prophylactic oophorectomy and postoperative adjuvant therapy with aromatase inhibitors may be a promising treatment option for deep angiomyxoma to optimize the outcome of surgical treatment. Long-term follow-up is required to monitor for the late and/or local recurrence of deep angiomyxoma and possible adverse effects of adjuvant hormonal therapy.

Cytopathology of rare gastric mesenchymal neoplasms: A series of 25 cases and review of literature.

BACKGROUND: Gastrointestinal stromal tumour (GIST) is the most common mesenchymal neoplasm arising in the stomach. However, a number of other rare mesenchymal neoplasms do occur at this anatomic site, which often presents a diagnostic challenge for cytopathologists on endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). Our study aims to selectively present the clinico-radiological and cytopathological characteristics of these rare "non-GIST" neoplasms, as well as their differential diagnoses. MATERIAL AND METHODS: We performed a 20 year retrospective search in the cytopathology database of our two large medical institutions for non-GIST mesenchymal neoplasms arising in the stomach and diagnosed on EUS-FNA. Data regarding the patients' demographics and radiological findings were analysed. All available cytopathology specimens were reviewed. The cytomorphological characteristics and the accompanying immunohistochemical stains, when available, were subsequently analysed. RESULTS: Twenty-five cases of gastric mesenchymal tumours were selectively included in the study after excluding all cases of GIST (n = 113) diagnosed on FNA. These cases included 10 leiomyomas (40%), eight schwannomas (32%), five glomus tumours (20%), one perivascular epithelioid cell neoplasm, and one desmoid tumour. The specimen cellularity was variable and ranged from hypocellular to highly cellular. Most smears were composed of spindle cells with a few showing epithelioid morphology. Cell blocks were available in 20 cases and a range of immunohistochemical ancillary studies were performed. DOG-1, c-KIT, smooth muscle actin (SMA), and S100-protein were the most common immunomarkers done. CONCLUSION: Our study highlights important cytomorphological characteristics of rare mesenchymal neoplasms arising in the stomach. In the appropriate clinical setting and with the help of immunohistochemistry, an accurate diagnosis of these neoplasms can be achieved.

Expanding the spectrum of GLI1-altered mesenchymal tumors-A high-grade uterine sarcoma harboring a novel PAMR1::GLI1 fusion and literature review of GLI1-altered mesenchymal neoplasms of the gynecologic tract.

GLI1-altered mesenchymal tumors comprise a group of seemingly unrelated entities, including pericytoma with t(7;12) translocation, plexiform fibromyxoma, gastroblastoma, malignant epithelioid neoplasm with GLI1 rearrangements, and GLI1-amplified mesenchymal neoplasms. Herein, we report a high-grade uterine sarcoma harboring a novel PAMR1::GLI1 fusion and present a literature review of GLI1-altered mesenchymal neoplasms of the gynecologic tract. A 57-year-old female presented with an abdomino-pelvic mass, felt since a decade prior. Magnetic resonance imaging showed a heterogenous myometrial mass extending beyond the serosa. The patient underwent oncologic surgical resection. Gross examination revealed a perforated multi-nodular uterine tumor (21 cm) with a firm white and soft fleshy cut surface, featuring hemorrhage and necrosis. The tumor was morphologically heterogenous, disclosing frankly sarcomatous areas composed of pleomorphic spindle and focally epithelioid cells, intermingled with a component of low-grade spindle cells arranged in fascicles. There was a rich vascular network and zones of necrosis with peripheral amianthoid-like collagen plaques. Lymphovascular invasion and metastasis to lymph nodes and omentum were present. The tumor was immunopositive for CD10 and cyclinD1, and negative for cytokeratins, myogenic, melanotic, and hormonal markers. ArcherTM Fusion Sarcoma Assay detected PAMR1(exon1)::GLI1(exon4) fusion, confirmed on RT-PCR and Sanger sequencing. The patient received chemo-radiotherapy, however, developed metastatic recurrence and demised 18 months post-surgery. Altogether, this is a rare and diagnostically challenging case of a uterine sarcoma harboring a novel GLI1 fusion. Emerging GLI/Hedgehog inhibitors provide clinical relevance to recognizing these tumors in modern pathology.

Mesenchymal neoplasms of the urinary bladder: a comprehensive review with focus on cross-sectional imaging findings.

Mesenchymal neoplasms of the urinary bladder are exceedingly rare and display remarkable diversity. These tumors demonstrate distinct pathological features as well as variable biological behavior and cross-sectional imaging findings. The rarity of tumors, nonspecific symptoms and seemingly normal cystoscopic findings (particularly with small and exophytic tumors) frequently lead to misdiagnosis or missed diagnosis. While some tumors display characteristic cross-sectional imaging findings that may suggest a diagnosis, imaging findings are mostly nonspecific. Histopathological examination is required for accurate diagnosis, management and prognostication. The purpose of this article is to review the cross-sectional imaging findings of a diverse spectrum of mesenchymal tumors of the urinary bladder.

[Lipoblastoma-like tumor of the vulva: A case report and review of the literature]. / Tumor vulvar similar a lipoblastoma: descripción de un nuevo caso y revisión de la literatura.

Lipoblastoma-like tumor of the vulva (LBLTV) was first described as a benign mesenchymal neoplasia; it was not recognized as a separate diagnosis in the 2013 WHO classification of soft-tissue tumors. To date, only 19 cases have been reported. LBLTV differential diagnosis includes other tumors of the vulvoperineal region and tumors with adipocytic differentiation, most of which are benign and thus a misdiagnosis has few clinical consequences. However, LBLTV may also mimic some aggressive lipomatous neoplasms. We describe a case of LBLTV in a 28 year-old woman and review the literature.

Tumor vulvar similar a lipoblastoma: descripción de un nuevo caso y revisión de la literatura / Lipoblastoma-like tumor of the vulva: A case report and review of the literature

El tumor vulvar similar a lipoblastoma (LBLTV) fue descrito inicialmente como una neoplasia mesenquimal benigna. Desde entonces, se han reportado únicamente 19 casos. Además, esta entidad no ha sido reconocida aún como diagnóstico separado en la clasificación de la OMS (2013) de los tumores de tejido blando. El diagnóstico diferencial de LBLTV incluye otros tumores de la región vulvoperineal, así como tumores con diferenciación adipocítica, la mayoría de ellos benignos. Por tanto, un diagnóstico erróneo aporta pocas consecuencias clínicas. Sin embargo, LBLTV puede imitar también algunas neoplasias lipomatosas agresivas. Describimos aquí un nuevo caso de LBLTV en una mujer de 28 años, así como una revisión de la literatura.(AU)

Lipoblastoma-like tumor of the vulva (LBLTV) was first described as a benign mesenchymal neoplasia; it was not recognized as a separate diagnosis in the 2013 WHO classification of soft-tissue tumors. To date, only 19 cases have been reported. LBLTV differential diagnosis includes other tumors of the vulvoperineal region and tumors with adipocytic differentiation, most of which are benign and thus a misdiagnosis has few clinical consequences. However, LBLTV may also mimic some aggressive lipomatous neoplasms. We describe a case of LBLTV in a 28 year-old woman and review the literature.(AU)

[Soft tissue tumours with FN1 (Fibronectin 1) fusion gene]. / Tumeurs des tissus mous avec fusion du gène FN1 (Fibronectine 1).

Translocations involving FN1 gene have been described in several tumours, which share the presence of a cartilaginous matrix with or without calcifications and a good prognosis. They encompass: soft tissue chondroma, synovial chondromatosis, calcifying aponeurotic fibroma, phosphaturic mesenchymal tumour and a new spectrum of tumours: "the calcified chondroid mesenchymal neoplasms". We review all the clinical, histopathological and molecular data of these tumours and discuss the differential diagnoses.

Role of the Immunohistochemical ZEB1 Expression in Uterine Mesenchymal Neoplasms.

The distinction of mesenchymal tumors of the uterus is a frequent diagnostic challenge in gynecologic pathology. Especially, distinguishing low-grade endometrial stromal sarcoma (ESS) from leiomyoma or distinguishing low-grade ESS from high-grade ESS can be difficult. Epithelial-mesenchymal transition (EMT) is a physiological and pathological process in which epithelial cells lose their morphological features, become elongated and acquire mesenchymal traits. The signaling pathway of Zinc finger E-box binding homeobox 1 (ZEB1) is one of the most significant pathways involved in the EMT process and it has a crucial role in cancer progression, metastasis, and therapy resistance. We studied a series of 69 uterine mesenchymal neoplasms including 18 endometrial stromal sarcomas (10 cases of low grade and 8 cases of high grade endometrial stromal sarcomas), 26 leiomyosarcomas (8 cases of grade 1 and 19 cases of grade 2-3 leiomyosarcomas), 15 leiomyomas, and 10 rhabdomyosarcomas, using an antibody ZEB1. We graded the leiomyosarcomas depending on the FNCLCC grading system. It was observed that leiomyosarcoma was more intensely stained with ZEB1 than leiomyoma (P < 0.001) and high-grade ESS was significantly more intensely stained with ZEB1 protein than low-grade ESS (P < 0.004). It also was observed that high-grade leiomyosarcoma was significantly more intensely stained with ZEB1 protein than low-grade leiomyosarcoma (P < 0.000). Our data suggest that Zeb1 can be used to differentiate high-grade sarcomas from their low-grade counterparts as well as benign and malignant smooth muscle tumors of the uterus.

Mesenchymal/non-epithelial mimickers of neuroendocrine neoplasms with a focus on fusion gene-associated and SWI/SNF-deficient tumors.

Mimickers of neuroendocrine neoplasms (NEN) include a number of important pitfall tumors. Here, we describe our experience with mesenchymal mimics of NENs to illustrate their spectrum and draw the attention particularly to a group of mesenchymal/non-epithelial neoplasms (MN) that combine epithelioid histology with neuroendocrine (NE-) features and peculiar genetic abnormalities. In a consultation series of 4498 cases collected between 2009 and 2021, 2099 neoplasms expressing synaptophysin and/or chromograninA were reviewed and analyzed. A total of 364 (18%) were diagnosed as non-NENs, while the remaining tumors were NEN. The group of mesenchymal/non-epithelial neoplasms with NE-features (MN-NE) included 31/364 (8%) cases. These mostly malignant neoplasms showed an epithelioid morphology. While all but one tumor expressed synaptophysin, mostly patchy, only 10/29 (34%) co-expressed chromograninA. A total of 13/31 (42%) of the MN-NE showed EWSR1-related gene fusions (6 Ewing sarcomas, 5 clear cell sarcomas, and 1 desmoplastic small round cell tumor, 1 neoplasm with FUS-CREM gene fusion) and 7 (23%) were SWI/SNF (SMARCB1 or SMARCA4)-deficient neoplasms. The remaining MN-NE included synovial sarcoma, sclerosing epithelioid mesenchymal neoplasm, melanoma, alveolar soft part sarcoma, solitary fibrous tumor, and chordoma. A total of 27/31 MN-NE were from the last 8 years, and 6 of them were located in the pancreas. Eleven MN-NE were initially diagnosed as neuroendocrine carcinomas (NECs). MN-NE with epithelioid features play an increasing role as mimickers of NECs. They mostly belong to tumors with gene fusions involving the EWSR1 gene, or with SWI/SNF complex deficiency. Synaptophysin expression is mostly patchy and chromograninA expression is infrequent in MN-NE of this series and data extracted from literature.

Non-gastrointestinal stromal tumours soft tissue sarcomas: an update.

Soft tissue sarcomas (STS) encompass a diverse family of neoplasms of mesenchymal origin, marked by significant heterogeneity in terms of physiopathology, molecular characterisation, natural history and response to different therapies. This review aims to summarise the current strategies for the management of patients with STS, including surgery, systemic treatments and radiation therapy, along with considerations applicable to the most frequent subtypes, as well as particularities associated with less common and specific histologies. It also provides insights into upcoming strategies to tackle this challenging group of diseases.

Rare malignant glomus tumor of the stomach with liver metastases.

We report a case of a 72-year-old male admitted in our Unit with anemia and a 10 cm liver neoplasm. Computed tomography scan showed 2 lesions respectively in the II, III and, VIII segment of the liver. Surgical resection of the larger liver mass was performed and the tumor appeared as a solid-cystic mass and a diagnosis of malignant mesenchymal tumor not otherwise specified, was made. One month later a Computed tomography scan detected a dishomogeneous gastric mass, 6 cm in diameter, in the greater curvature, confirmed by esophagogastroduodenoscopy. The pathological diagnosis from endoscopic biopsy revealed a mesenchymal tumor requiring surgical removal for accurate diagnosis. The patient underwent relaparotomy and gastric resection and the pathological findings gave a diagnosis of a rare malignant glomic tumor of the stomach confirmed by the revision of previously performed hepatic resection classified as secondary lesion.

Mazabraud's Syndrome: A Case Report and Up-To-Date Literature Review.

OBJECTIVE: Mazabraud's syndrome is a rare form of bone fibrous dysplasia associated with intramuscular myxomas. Fibrous dysplasia, is generally localized to pelvis and femur and it results in a fragile bone with deformities, pain, pathological fractures and functional impairment. Intramuscular myxomas, are rare benign mesenchymal neoplasms that exceptionally may evolve to malignant forms. METHODS: This case report describes a 66-year-old woman with Mazabraud's Syndrome (MS), characterized both by monostotic right femur fibrous dysplasia and by a solitary intramuscular myxoma at the right quadriceps muscle, that underwent a long-term treatment (4 years) with intravenous zoledronic acid. RESULTS: Zoledronic acid therapy rapidly lowered bone pain together with a reduction of intramuscular myxoma volume, but did not affect the extension of fibrous dysplasia. No adverse effects have been observed during treatment. CONCLUSION: Highly active bisphosphonates are commonly used for the treatment of bone metabolic disorders and they are generally well tolerated. Zoledronic acid may represent a promising alternative to surgical intervention in MS, although its use in rare form of bone fibrous dysplasias is still controversial.

Mesenchymal Neoplasms of the Genitourinary System: A Selected Review with Recent Advances in Clinical, Diagnostic, and Molecular Findings.

Mesenchymal neoplasms of the genitourinary (GU) tract often pose considerable diagnostic challenges due to their wide morphologic spectrum, relative rarity, and unexpected incidence at GU sites. Soft tissue tumors arise throughout the GU tract, whether from adventitia surrounding or connective tissues within the kidneys, urinary bladder, and male and female genital organs. This selected article focuses on a subset of these lesions, ranging from benign to malignant and encompassing a range of patterns of mesenchymal differentiation, where recent scholarship has lent greater insight into their clinical, molecular, or diagnostic features.