Atypical Spindle Cells Research Articles

Rare Presentation of Extraskeletal Osteosarcoma Mimicking Phyllodes Tumor

Abstract Introduction/Objective A 57-year-old female presented with a palpable mass in the left breast, measuring up to 9 cm by ultrasound. core needle biopsy identified an atypical spindle cell lesion. The differential diagnosis included a metaplastic carcinoma, borderline phyllodes tumor, malignant phyllodes tumor with potential sarcomatous transformation. Methods/Case Report Histological examination of the tumor was performed, and immunohistochemical stains were conducted to characterize the lesion. Further consultation with a specialized pathologist at the University of Michigan was sought to confirm the diagnosis. Molecular analysis was performed to assess for specific genetic alterations and expression patterns. The histological examination revealed a proliferation of atypical spindle cells forming a fascicular and storiform pattern, with numerous large, pleomorphic, multinucleated tumor cells and a high mitotic rate. Immunohistochemical stains showed strong positivity for CD10 and vimentin, with focal weak expression for desmin, and negativity for a broad panel of cytokeratins and other markers. Consultation with Dr. Abbott at the University of Michigan supported the diagnosis of extraskeletal osteosarcoma. Molecular analysis revealed PD-L1 expression and absence of NTRK gene fusions. FISH analysis showed suggestive alterations including loss of BRAF gene, loss of MYC, and suggestive gains or polysomy of PTEN gene. Results (if a Case Study enter NA) NA Conclusion The case represents a rare presentation of extraskeletal osteosarcoma in the breast, with distinctive histological and immunohistochemical features. The comprehensive workup including histology, immunohistochemistry, and molecular analysis aids in accurate diagnosis and potential therapeutic implications. Further research may elucidate the underlying mechanisms and treatment options for this uncommon malignancy.

Metastatic Carcinosarcoma with a Sarcomatous Predominance?

Abstract Introduction/Objective Uterine carcinosarcoma (CS), also known as Malignant Mixed Müllerian Tumor, is a malignancy characterized by mixed epithelial and mesenchymal components. It is rare and aggressive, most frequently occurring in elderly, postmenopausal women with a median age of 65 years. CS has a tendency to metastasize with an overall poor prognosis. Fine needle aspiration can be useful in identifying metastatic disease, however, demonstration of both sarcomatous and carcinomatous components can be difficult. Methods/Case Report Our patient is a 68 year old female who was first diagnosed with endometrial carcinosarcoma on an endometrial biopsy in 2022. She subsequently underwent a total abdominal hysterectomy with radical dissection, bilateral salpingo-oophorectomy, upper vaginectomy, sentinel lymph node dissection as well as chemotherapy. Immunohistochemistry for MLH1, MSH2, MSH6 and PMS2 all showed intact nuclear expression. Remission was achieved for about a year, after which she was found to have a moderate right sided pleural effusion with right lower lung infiltrates. Also, a right upper lobe mass was reported on chest CT scan. Paracentesis was performed and cytology was consistent with predominantly atypical spindle cells accompanied by a mixed inflammatory infiltrate. Immunohistochemical stains were performed on the cell block, tumor cells were positive for smooth muscle actin, vimentin and negative for desmin, S-100, SOX-10, CD34, P63, TTF-1 and pancytokeratin. Cytology diagnosis was rendered as malignant cells present, consistent with metastatic CS. A subsequent lung mass core biopsy also confirmed the diagnosis. Results (if a Case Study enter NA) NA Conclusion The cytomorphological features in effusion samples from metastatic CS have the carcinomatous component readily identifiable, and only a minority of effusion samples show additional sarcomatous component. The exact diagnosis of CS may not be possible due to the absence of sarcomatous components. Alternatively, as we present in this rare case of metastatic CS, the sarcomatous component in the form of abundant atypical oval to spindle cells with hyperchromatic nuclei may be the only form of malignant cells present in the specimen. Careful morphological assessment of architectural patterns, a good past medical history, availability of cell blocks and immunohistochemistry are vital in providing an accurate diagnosis in such rare cases of metastatic CS.

8078 TERT Positive Thyroid Nodule in the Setting of Metastatic Melanoma

Abstract Disclosure: E. Langnas: None. S. Chao: None. K.M. Gomes: None. A. Bhan: None. Metastatic disease to the thyroid gland is uncommon with a reported incidence of up to 4% in post-surgical specimens. Lung cancer is the most common primary tumor site in autopsy series. Clinically, renal cell carcinoma is the most common primary tumor site. Metastatic melanoma to the thyroid gland is clinically rare, however, in autopsy series, it has been reported with incidence of up to 39%. A 61-year-old man presented to the endocrinology clinic for an incidentally detected thyroid nodule. He had recently presented with a chronic cough, prompting a chest x-ray that revealed pulmonary nodules. Subsequent computed tomography (CT) showed numerous bilateral lung nodules measuring up to 2.5 cm and an incidental thyroid nodule. Ultrasound of the thyroid identified a 2.7 cm mixed cystic-solid right thyroid nodule. No risk factors for thyroid cancer were identified. His TSH was 3.51uIU (0.45 - 5.33 uIU/mL). The thyroid nodule was biopsied, and pathology revealed atypical spindle cells with irregular nuclear membranes and scattered histiocytes. A further review with cytopathology suggested non-thyroidal origin of the cells. Molecular testing with AFIRMA reported a telomerase reverse transcriptase (TERT) promoter mutation at C228T. The sequencing was negative for TERT C250T, BRAF, RET, PETC1, PTC3 and MTC. Due to concerns about metastatic disease, a positron-emission tomography (PET)-CT was conducted, revealing hypermetabolic lesions in numerous bilateral lung nodules, right thyroid nodule, porta hepatis lymph node, and a soft tissue nodule within the greater curvature of the gastric body. Subsequent biopsies of the right lung and gastric body confirmed the diagnosis of metastatic melanoma. On further questioning, it was found that the patient had a history of a skin lesion on his back that was excised several years ago with pathology reporting tumoral melanosis. Malignant melanoma has a poor prognosis due to high recurrence and metastatic rates. In melanoma, TERT promoter mutations are the most common mutations in noncoding regulatory regions. TERT C228T mutations and C250T mutations are seen in malignant melanoma and studies have shown that TERT promoter mutations are associated with aggressive clinical behavior. These TERT promoter mutations can also be seen in various other cancers including primary thyroid cancers with a similar association with more aggressive thyroid tumor characteristics. Our case describes a patient with a thyroid nodule and molecular testing noting a TERT promoter mutation. Both primary thyroid cancer and metastatic disease to the thyroid should be considered in these cases. This case also highlights the importance of obtaining a thorough history of prior malignancy in patients with thyroid nodules to assess the risk of metastatic disease. Presentation: 6/1/2024

Atypical Spindle Cell/Pleomorphic Lipomatous Tumor: A Review and Update.

Atypical spindle cell/pleomorphic lipomatous tumor (ASCPLT) is a rare and recently described adipocytic neoplasm that primarily occurs in the subcutis of the limbs and limb girdles, particularly of middle-aged adults. It has locally recurrent potential if incompletely excised but no risk for distant metastasis. ASCPLT is histologically similar to spindle cell/pleomorphic lipoma and atypical lipomatous tumor and shows a mixture of atypical spindle cells, adipocytes, lipoblasts, floret-like multinucleated giant cells, and/or pleomorphic cells. It has been recently recognized that ASCPLT can undergo sarcomatous transformation. However, the biological significance of morphological sarcomatous transformation in ASCPLT remains uncertain. Immunohistochemically, the tumor cells show variable expression of CD34, S-100 protein, and desmin. Loss of nuclear Rb expression is observed in the majority of cases. ASCPLT lacks MDM2 gene amplification but can show RB1 gene deletion in a significant subset of cases. Complete surgical excision is the treatment of choice. This review provides an overview of the current knowledge on the clinicoradiological features, pathogenesis, histopathology, and treatment of ASCPLT. In addition, we will discuss the differential diagnosis of this new entity.

SATB2 expression in oral sarcomatoid (spindle cell) squamous cell carcinoma: clinicopathologic and immunophenotypic characterization of 10 cases

ObjectiveSarcomatoid squamous cell carcinoma (sSCC) represents an uncommon histopathologic variant of SCC. We examined the clinicopathologic and immunophenotypic characteristics, including SATB2 expression, of 10 oral sSCCs. Study DesignArchived sSCC cases diagnosed during the period 2000-2023 were retrieved. Lesions lacking proper histomorphologic features or adequate immunohistochemical confirmation were excluded. Patient age, sex and lesion location were recorded. All cases were immunostained against SATB2 (Clone EP281; Cell Marque). ResultsTen oral sSCCs were identified (M:F ratio = 1.5:1; age range = 47-82y, median = 74.5y). Tongue was the most common anatomic site. Lesions presented as fungating or ulcerated, polypoid and indurated masses. Microscopically, most tumors demonstrated an infiltrative population of atypical spindle cells organized in slender cords or fascicles. Rhabdoid/plasmacytoid morphology was observed in 3 cases. Immunohistochemically, all cases exhibited strong, focal-to-diffuse positivity for pancytokeratin, p63 and/or p40. Patchy, moderate-to-strong SATB2 staining was seen in 4 oral sSCCs, while 4 additional cases showed rare, weak-to-moderate expression. ConclusionsOral sSCC is uncommon and primarily exhibits spindled histomorphology, although rhabdoid/plasmacytoid features may be observed. A battery of epithelial and non-epithelial markers is required for proper diagnosis. Positive SATB2 immunostaining in oral sSCCs may pose a potential diagnostic pitfall, particularly in small biopsy specimens.

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.

A Case Series of Primary Cutaneous Sarcomatoid Carcinoma With Aberrant Smooth Muscle Actin Expression: A Clinicopathologic and Immunophenotypic Study.

Primary cutaneous sarcomatoid squamous cell carcinoma can show significant histologic overlap with other malignant spindle cell tumors, posing a diagnostic challenge. Even with a wide array of immunohistochemical markers, the exact line of differentiation can be a challenge to identify in some cases. The picture is further complicated by the aberrant expression of myofibroblastic markers [such as smooth muscle actin (SMA)] by these neoplasms, along with a concomitant loss of conventional epithelial markers. The histologic differential diagnoses of primary cutaneous sarcomatoid squamous cell carcinoma include desmoplastic melanoma, leiomyosarcoma, and spindle cell atypical fibroxanthoma/pleomorphic dermal sarcoma (AFX/PDS). A retrospective analysis of 16 cases of PCSSCCs with SMA expression, obtained from large academic institutions, was performed and is summarized below. The tumors were in the scalp (6 cases), arm (4 cases), leg (2 cases), face (2 cases), hand (1 case), and neck (1 case). Immunohistochemical studies were performed in all cases with the following antibodies: AE1/AE3, CAM 5.2, MNF-116, p63, p40, CK5/6, S-100, SOX10, SMA, desmin, calponin, H-caldesmon, CD10, CD68, CD163, and CD34. Histopathologically, all cases were classified as high-grade malignant poorly differentiated neoplasms. Tumors were characterized by an infiltrative neoplasm that involved the entire reticular dermis and, in 7 cases, the subcutaneous fat. Three cases were associated with a well-differentiated squamous cell component. The neoplasms were composed of atypical spindle and epithelioid cells arranged in long and intersecting fascicles. All neoplasms were positive for epithelial markers (at least 1 marker), and all cases were strongly positive for SMA. Our data emphasize the diagnostic utility of multiple epithelial markers as a first screening tool in the detection and workup of malignant cutaneous sarcomatoid neoplasms. Awareness of SMA expression in these tumors can complicate its diagnosis, and it is important to recognize this aberrant immunophenotype to facilitate definitive diagnosis and avoid misdiagnosis.

Giant Atypical Spindle Cell Lipomatous Tumor of Retroperitoneal Origin Presenting with Lung Metastasis and Extension to the Thigh: A Case Report with Literature Review

AbstractRetroperitoneal liposarcomas are rare, and their variants, atypical spindle cell lipomatous tumor (ASCLT), are rarer. Though ASCLTs are benign, they have high recurrence despite complete surgical excision. We present a rare case of a 22-year-old male presented with insidious-onset, and gradually progressive swelling over left inguinofemoral, and iliac fossa region. Also, the patients had a history of weight loss, pricking-type pain radiating to left lower limb, and breathlessness on exertion. Contrast-enhanced computed tomography (CECT) abdomen revealed a large well-defined heterogeneously enhancing soft mass located in pelvis, and involving left-sided iliopsoas muscle suggestive of retroperitoneal soft tissue sarcoma and CECT thorax showed metastasis. The CT-guided core biopsy led to the definitive diagnosis of low-grade ASCLT. Subsequently, the patient was initiated on concurrent neoadjuvant chemoradiotherapy followed by complete surgical excision. The findings in this report make it critical to enhance our understanding of this rare tumor, with surgery being the best treatment option.

Atypical spindle cell proliferation of indeterminate biological potential

Atypical spindle cell proliferation of indeterminate biological potential

YAP1∷KMT2A fusion-positive sarcoma: An emerging soft tissue tumor entity with morphological features resembling a sclerosing epithelioid fibrosarcoma.

Sclerosing epithelioid fibrosarcoma (SEF) and low-grade fibromyxoid sarcoma (LGFMS) constitute a morphological continuum with certain overlapping histopathological features and MUC 4 immunopositivity. SEF is characterized by EWSR1 gene rearrangement, is relatively more aggressive and shows a limited response to chemotherapy. Lately, a subset of tumors with morphological features of SEF, but lacking MUC4 immunostaining and EWSR1 gene rearrangement have been observed. We report the first case of YAP1∷KMT2A-positive sarcoma from the Indian subcontinent along with a review of similar tumors reported previously. A case of 31-year-old male presented with a 3 cm painful lump in the right suboccipital region. Histopathological examination of the excised specimen revealed a cellular tumor composed of atypical spindle and epithelioid cells, exhibiting moderate nuclear pleomorphism, arranged in cords, embedded in a dense collagenous/hyalinized stroma. By immunohistochemistry, the tumor cells were diffusely positive for cyclin D1 and negative for MUC4, desmin, myogenin, β-catenin, STAT6, myoD1, SMA, and S100P. By fluorescence in-situ hybridization, EWSR1 gene rearrangement was negative. Next-generation sequencing (NGS) revealed YAP1exon5∷KMT2Aexon4 fusion. Given a positive resection margin, he underwent a revision surgery involving wide local excision of the lesion including the outer table of the occipital bone followed by image-guided radiation therapy. Over 2 years of his follow-up, the patient is alive with no evidence of recurrence. Thus, YAP1∷KMT2A positive sarcomas have distinct molecular and overlapping histopathological features with SEF, with relatively less aggressive disease course. Documentation of additional similar tumors with long-term follow-up is required.

Challenges in Distinguishing Rectal Leiomyosarcoma from Ovarian Malignancy: A Diagnostic Conundrum

Introduction: Rectal leiomyosarcoma is a rare malignant mesenchymal tumor accounting for <0.1% of all malignant colorectal neoplasms and carries a grave prognosis. Case Presentation: A 50-year-old postmenopausal, P3L3 woman presented with complaints of abdominal pain for two months, dark-colored loose stools, 10-15 episodes per day for 2-3 months, and gradual weight loss for 4-5 months. On ultrasonography and MRI of the pelvis, a large irregular lobulated ill-defined solid lesion was seen arising from the right side of the pelvis measuring 14x8x14cm. The right ovary was not observed to be separate from the mass. There was omental thickening and peritoneal deposits with ascites. The final impression suggested a right-sided malignant ovarian mass with peritoneal dissemination (ORADS-5) with a differential leiomyosarcoma. Her tumor markers (CA- 125; CA19-9, and CEA) were raised. Given the strong dilemma between ovarian malignancy and leiomyosarcoma and the advanced stage of the disease, the patient was planned for an ultrasound-guided biopsy of the lesion. The histopathological report revealed atypical spindle cell proliferation with myoid features with the presence of multiple mitotic figures. The diagnosis of rectal leiomyosarcoma was further confirmed with immunohistochemical tests, which were positive for actin and desmin and negative for CD 117 and S100. The patient was referred to oncosurgeon for further management and was planned for surgical resection followed by chemotherapy with intravenous doxorubicin. Conclusion: Rectal leiomyosarcoma is commonly misdiagnosed as ovarian malignancy because of its exophytic growth and similar clinical features at the time of the presentation. Hence, clinicians must be aware of these differentials for the successful management of cases.

Primary NTRK -rearranged Spindle Cell Neoplasm of the Gastrointestinal Tract: A Clinicopathological and Molecular Analysis of 8 Cases.

NTRK-rearranged spindle cell neoplasm occurs predominantly in the superficial or deep soft tissues of extremities or trunk. Occurrence in the visceral organs is extremely rare. Herein, we describe 8 cases of NTRK-rearranged spindle cell neoplasm that arose primarily in the gastrointestinal tract. Patients included 5 males and 3 females with age at presentation ranging from 6 to 63 years (median: 29.5 years). Tumors occurred in the colon (n=3), small intestine (n=2), rectum (n=2), and stomach (n=1). Tumor size ranged from 3.5 to 9cm (median: 5cm). Morphologically, 4 tumors were low-grade, composed of haphazard or intertwining fascicles of spindle cells, with prominent interstitial collagen fibers and ring-like perivascular hyalinization being present in 2 tumors. The other 4 tumors were histologically high-grade sarcomas, consisting of sweeping fascicles of atypical spindle cells showing increased cellularity and brisk mitotic activity. Immunohistochemically, 6/6 cases (100%) showed diffuse and strong cytoplasmic staining of pan-TRK. Variable expression of TrkA, CD34, and S100 was noted in 5/5 (100%), 5/8 (62.5%), and 4/7 (57.1%) cases, respectively. Fluorescence in situ hybridization analysis showed NTRK1 rearrangement (n=7) and NTRK2 rearrangement (n=1). In cases with available materials, RNA sequencing identified LMNA::NTRK1 (n=3), TPM3::NTRK1 (n=2), and STRN::NTRK2 (n=1) fusions. At follow-up (range: 4 to 30 months; median: 12.5 months), 6 of 7 patients who underwent surgery had no evidence of disease at last follow-up. One patient was succumbed to the disease at 12 months despite adjunctive treatment with TRK inhibitor larotrectinib after surgery. One patient was treated with larotrectinib alone. He showed significant response at 7 months after treatment. NTRK-rearranged spindle cell neoplasm represents an exceptionally rare entity in the gastrointestinal tract. The presence of interstitial collagen fibers and ring-like perivascular hyalinization and co-expression of CD34 and S100 are diagnostic clues to low-grade neoplasms. However, high-grade sarcomas pose a considerable diagnostic challenge to pathologists owing to the lack of specific features. The final diagnosis relies on molecular assays. Patients with advanced disease may benefit from TRK inhibitor treatment.

Atypical Spindle Cell/Pleomorphic Lipomatous Tumor With Sarcomatous Transformation: Clinicopathologic and Molecular Analysis of 4 Cases

Atypical spindle cell/pleomorphic lipomatous tumor (ASPLT) is a recently described adipocytic tumor predominantly affecting the subcutaneous soft tissues of adults. Previous studies have shown that ASPLT follows a benign clinical course with a 4% to 12% local recurrence rate and no risk of dedifferentiation. Herein, we describe the clinicopathologic and molecular findings of 4 cases of ASPLT showing unequivocal sarcomatous transformation. Three patients were male and one was female, aged 65, 70, 74, and 78 years. Two cases presented as mass-forming lesions, while 1 case was incidentally discovered. The tumors measured 30, 55, 80, and 110 mm and occurred in the chest wall (n = 2) or arm (n = 2); all were subcutaneous. Microscopically, they showed a biphasic appearance comprising a low-grade ASPLT component and a high-grade sarcomatous component. The low-grade components showed features in the spectrum of either atypical pleomorphic lipomatous tumor (n = 2) or atypical spindle cell lipomatous tumor (n = 2). The high-grade components displayed leiomyosarcoma-like (n = 2), pleomorphic liposarcoma-like (n = 1) or undifferentiated sarcoma-like (n = 1) morphology. On immunohistochemistry, tumors were negative for MDM2 and showed loss of RB1 expression. In addition, the leiomyosarcoma-like areas seen in 2 cases were positive for smooth muscle actin and H-caldesmon. Single-nucleotide polymorphism array, performed in 3 cases, showed deletions of TP53, RB1, and flanking genes in both components. In contrast, the sarcomatous components showed more complex genomic profiles with rare segmental gains and recurrent loss of PTEN (n = 3), ATM (n = 2), and CDKN2A/B (n = 2) among other genes. Whole exome sequencing identified a TP53 variant in one case and an ATRX variant in another, each occurring in both tumor components. Limited clinical follow-up showed no recurrence or metastasis after 1 to 13 months (median, 7.5 months) postsurgical excision. Altogether, our data support that ASPLT can rarely develop sarcomatous transformation and offer insights into the molecular mechanisms underlying this event.

Granulation tissue-like spindle cell (sarcomatoid) carcinoma of the head and neck: a deceptively bland-looking underdiagnosed malignancy

The diagnosis of head and neck spindle cell squamous carcinoma (SC-SCC) is often challenging. Lesions with a prominent inflammatory infiltrate and reactive vessels may have a granulation tissue-like appearance, therefore being difficult to distinguish from reactive lesions, like contact ulcers, post-intubation granulomas, inflammatory pseudotumors, or benign vascular lesions. In this study, we analyzed the clinicopathological features of a series of 17 head and neck SC-SCC with granulation tissue-like appearance. All patients, but two, were males, ranging in age between 57 and 80 years. The larynx was the most frequently affected site (n = 12), followed by the tongue (n = 4). One tumor was hypopharyngeal. Most consult cases were submitted with benign suggestion or because of unexpected recurrences of granulation tissue polyps. Histologically, all lesions consisted of an ulcerated polypoid proliferation of moderately to markedly atypical spindle cells, with a minor component of conventional invasive or in situ squamous carcinoma. At least one cytokeratin cocktail was positive in 13 cases. The staining was limited to a few neoplastic cells in most cases. Positivity for p63, p40, and cytokeratins 5/6 was detected only in the conventional squamous cell carcinoma component, when present. ALK1 was negative in all cases. Sixteen cases were tested for p53 and all showed aberrant expression (12 diffusely positive and 4 of null-phenotype). The diagnosis of granulation tissue-like SC-SCC is challenging due to the close clinical and histological overlap with several benign conditions. Since the expression of epithelial markers is limited, the use of an immunohistochemical panel including p53 is recommended.

Intracystic Malignant Adenomyoepithelioma of the Breast: A Case Report and Review of Literature

Adenomyoepithelioma (AME) of the breast is a rare neoplasm with a biphasic proliferation of epithelial and myoepithelial cells. The authors report an unusual case of AME of 51-year-old woman. The AME was located in a cystic structure 6 cm in diameter as a solid nodular lesion with 2cm size. Immunohistochemically, the nodule was comprised with 2 cell population of tubular structures. First population of the glandular epithelial cells with dark cytoplasm showed the activity of CK7(+), CAM5.2(+), CK5/6(partly +), p63(-), CD10(-), S-100(-), αSMA(-). Second population of outer myoepithelial cells with clear cytoplasm displayed the activity of p63(+), CD10(+), CK14(+) CK5/6 (partly +), CK7(weakly +), CAM5.2(weakly +), S-100(+), αSMA(+). Beside them, cellular cluster of the inner epithelial cells with prominent nuclear as well as cellular atypia, and atypical spindle cell proliferation emanating from the myoepithelial component were also present. Thus, the nodule was diagnosed as malignant AME. One year after the lumpectomy, pulmonal metastasis of the breast tumor was also found. So far as we are concerned, such case of intracystic malignant AME of the breast has never been described. Regarding histogenesis of the neoplasm growing under the unusual environment, a consideration with review of literature was done.

HIV Associated Kaposi’s Sarcoma with Visceral Involvement and Rectal Bleeding

Abstract Introduction/Objective Kaposi’s sarcoma (KS) is one of the complications of advanced HIV disease and human herpes virus 8 (HHV-8) is the etiological agent. Most cases of KS are cutaneous and resolved with HIV treatment, few cases of KS present with visceral involvement and have a poor prognosis. Any part of the gastrointestinal tract (GIT) may be affected by KS, however visceral involvement without cutaneous lesions is extremely rare. KS has metastatic potential and can be fatal if treatment is not initiated immediately. Methods/Case Report A 29 years old homosexual man with a history of multiple sexually transmitted diseases and HIV infection (CD4: 331 cell/μL, CD4/CD8: 0.2, HIV RNA: 10542 copies/mL) presented to the emergency department in a hypovolemic state with hemoglobin of 6 g/dl. He received HAART 3 years ago but discontinued it due to the COVID pandemic. He had a history of recurrent and intermittent rectal bleeding which was exacerbated during the past 3 months. On physical examination, a bleeding rectal mass and bilateral inguinal adenopathy were noted. An imaging study was performed and showed a 14 cm anorectal mass extruding through the anal canal, with bilateral axillary, inguinal, pelvic side walls, iliac chains, and periaortic lymphadenopathy. Flow cytometry of the fresh biopsy tissue revealed a T cell-predominant lymphoid population with reversed CD4/CD8 ratio, compatible with the patient's known history of HIV, with no immunophenotypic evidence of lymphoma. Histopathologic examination of an excisional biopsy of the rectal mass showed mild to moderate atypical spindle cells arranged in vague fascicles and separated by slit-like vessels and extravasated red blood cells. Immunohistochemical (IHC) stain revealed the atypical spindle cells were positive for HHV-8, CD31, CD34, D2-40, BCL2, Vimentin, and Ki-67 (35%-highly proliferative) whereas these cells were negative for AE1/AE3, CK5/6, P40, CD45, Desmin, and S100. A diagnosis of KS was made. Results (if a Case Study enter NA) NA Conclusion We present a case of visceral KS without cutaneous involvement, which may pose a difficulty in diagnosis. The GIT, lungs, and lymph nodes are the relatively common sites that are affected by visceral KS. KS manifests various histopathological and clinical pictures, and a delay in diagnosis can cause a worse prognosis. The treatment options for KS are depending on the clinical presentation and the extension of the lesions. A combination of HAART, chemotherapy, and radiotherapy could be an effective treatment in the early stage of the disease.

Pseudoangiomatous Spindle Cell Lipoma: A Rare and Distinct Pattern of Lipomatous Tumors.

Pseudoangiomatous spindle cell lipoma is a rare pattern within the spindle cell lipoma spectrum that exhibits a remarkable histological pattern characterized by its resemblance to vascular lesions, creating a pseudoangiomatous appearance. Approximately 20 to 30 reports have been described in the literature. In this context, we present an intriguing report of pseudoangiomatous spindle cell lipoma showcasing a unique low-fat pseudo angiomatous pattern in a 61-year-old male patient presented with a 6-cm subcutaneous mass on his right arm, which was thoroughly investigated and subsequently excised. Microscopic examination revealed bland spindle cells infiltrates within a fibromyxoid stroma. Notably, the tumor exhibited distinctive branching and dilated vascular-like spaces that formed pseudopapillary (villiform) projections. Interestingly, the tumor displayed certain regions featuring mature adipose tissue components, alongside hyalinized blood vessels. No necrosis, atypical spindle cells, increased mitotic activity, or pleomorphic lipoblasts were observed. The immunohistochemical evaluation demonstrated diffuse positive staining for CD34 and negative staining for STAT6. This report of a low-fat pattern of pseudoangiomatous spindle cell lipoma underscores the importance of recognizing and characterizing rare entity subtype for accurate diagnosis and appropriate management. This report contributes to the expanding understanding of the diverse presentations of pseudo angiomatous spindle cell lipomas and underscores the significance of comprehensive histopathological assessment.

CYP1A1 immunohistochemistry is highly specific for angiofibroma of soft tissue among morphological mimics.

Angiofibroma of soft tissue (AFST) is a benign, morphologically distinctive tumour type that harbours recurrent AHRR::NCOA2 fusions in 60-70% of cases and shows a non-specific immunophenotype, expressing EMA in roughly half of cases. The AHRR::NCOA2 fusion results in increased expression of cytochrome P450 1A1 (CYP1A1); a recent study demonstrated CYP1A1 immunohistochemistry (IHC) to be moderately sensitive and highly specific for AFST. In this study, we sought to validate these findings in a larger independent cohort of 30 AFST, as well as 215 morphological mimics, including 30 solitary fibrous tumours, 29 myxoid liposarcomas, 28 low-to-intermediate grade myxofibrosarcomas (MFS), 20 atypical spindle cell lipomatous tumours (ASCLT), 20 cellular angiofibromas, 10 cases each of spindle cell lipoma, neurofibroma, malignant peripheral nerve sheath tumour, superficial angiomyxoma, cellular myxoma, soft tissue perineurioma and deep fibrous histiocytoma, and nine cases each of low-grade fibromyxoid sarcoma and mammary-type myofibroblastoma. We found CYP1A1 IHC to be 70% sensitive for AFST, with granular cytoplasmic staining in 21 of 30 tumours, and 98% specific, with staining in only five morphological mimics: two deep fibrous histiocytomas, one MFS, one cellular angiofibroma and one ASCLT. These findings confirm that CYP1A1 is 70% sensitive, consistent with the prevalence of AHRR::NCOA2 fusions that up-regulate this protein, and that it is highly specific among morphological mimics.

Uterine Sarcoma With EML4::NTRK3 Fusion: A Spectrum of Mesenchymal Neoplasms Harboring Actionable Gene Fusions.

NTRK gene fusions are part of a paradigm shift in oncology, arising as one of the main genomic alterations with actionability in the so-called "agnostic setting." In gynecologic pathology, the recent description of uterine sarcoma resembling fibrosarcoma and with NTRK rearrangements (NTRK-rearranged uterine sarcoma) highlights the importance of recognizing clinicopathological cues that can lead to genomic profiling. Herein, we report the case of a 43-year-old woman presenting with vaginal bleeding and pelvic mass. Histopathology of the tumor showed moderately atypical spindle cells arranged in long fascicles reminiscent of fibrosarcoma, along with immunohistochemical positivity for S100, CD34, and pan-tropomyosin receptor kinase. This prompted RNA-sequencing and the finding of a rare EML4::NTRK3 fusion. Clinical, histologic, and molecular findings are described, in addition to discussions regarding differential diagnoses and possible implications of the findings in clinical practice.

Solitary Fibrous Tumor of the Pancreas: Analysis of 9 Cases With Literature Review.

Solitary fibrous tumor (SFT) has been increasingly reported in various anatomic sites. However, it is still extremely rare in the pancreas. Herein, we present the first series of primary pancreatic SFTs. Nine cases of primary pancreatic SFTs were analyzed. The mean age was 60 years (36 to 76y) with no sex predilection. Six tumors were in the head, 3 were in the tail. On imaging studies, tumors were described as a hypervascular mass, 2 revealed cystic areas, and 3 were favored to be neuroendocrine tumors. On biopsy, 2 cases were diagnosed as atypical spindle cell tumor; one was misdiagnosed as suspicious for sarcoma, and another case as metastatic renal cell carcinoma. Two were diagnosed as low-grade sarcoma and low-grade stromal tumor on frozen sections. Grossly, tumors were well-demarcated with a median size of 4cm (0.9 to 15cm). Microscopically, they were composed of ovoid to spindle tumor cells with no significant mitotic activity and were arranged in alternating hypercellular and hypocellular areas. Staghorn-like vessels and entrapped pancreatic parenchyma were also detected within all tumors. Tumor cells revealed diffuse/strong nuclear STAT6 expression in 7 of 8, CD34 in 7 of 9, and bcl-2 in 4 of 4 tested cases. One tested tumor harbored NAB2 - STAT6 fusion. Eight patients with available follow-up data were free of disease at a mean follow-up of 76 months (3 to 189mo). SFT should be considered in the differential diagnoses of mesenchymal neoplasms of the pancreas. Immunohistochemical nuclear STAT6 expression is a characteristic feature of SFT. Primary pancreatic SFTs seem to have favorable biological behavior in our series.