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Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors that express smooth muscle and melanocytic makers. Diagnosis of PEComas can be challenging due to focal or lost expression of traditional immunohistochemical markers, limited availability of molecular testing, and morphological overlap with much more common smooth muscle tumors. This study evaluates the use of glycoprotein nonmetastatic melanoma protein B (GPNMB) immunohistochemical staining as a surrogate marker for TSC1/2/MTOR alteration or TFE3 rearrangement to differentiate PEComas from other mesenchymal tumors. Cathepsin K was also assessed for comparison. A total of 399 tumors, including PEComas, alveolar soft part sarcomas, and other histologic PEComa mimics, were analyzed using GPNMB and cathepsin K immunohistochemistry. GPNMB expression was seen in all PEComas and alveolar soft part sarcomas with the majority showing diffuse and moderate-to-strong labeling, whereas other sarcomas were negative or showed focal labeling. When a cutoff of diffuse and at least moderate staining was used, GPNMB demonstrated 95% sensitivity and 97% specificity in distinguishing PEComas from leiomyosarcoma, well-differentiated/dedifferentiated liposarcomas, and undifferentiated pleomorphic sarcomas. Cathepsin K with a cutoff of any labeling had lower sensitivity (78%) and similar specificity (94%) to GPNMB. This study highlights GPNMB as a highly sensitive marker for PEComas and suggests its potential use as an ancillary tool within a panel of markers for accurate classification of these tumors.
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Melanoma , Neoplasias de Células Epitelioides Perivasculares , Receptores Fc , Sarcoma , Humanos , Imuno-Histoquímica , Catepsina K/metabolismo , Melanoma/patologia , Biomarcadores Tumorais/metabolismo , Neoplasias de Células Epitelioides Perivasculares/diagnóstico , Neoplasias de Células Epitelioides Perivasculares/patologia , Glicoproteínas , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Glicoproteínas de MembranaRESUMO
Mesenchymal tumors with GLI1 fusions or amplifications have recently emerged as a distinctive group of neoplasms. The terms GLI1-altered mesenchymal tumor or GLI1-altered soft tissue tumor serve as a nosological category, although the exact boundaries/criteria require further elucidation. We examined 16 tumors affecting predominantly adults (median age: 40 years), without sex predilection. Several patients had tumors of longstanding duration (>10 years). The most common primary site was soft tissue (n = 9); other sites included epidural tissue (n = 1), vertebra (n = 1), tongue (n = 1), hard palate (n = 1), and liver (n = 1). Histologically, the tumors demonstrated multinodular growth of cytologically uniform, ovoid-to-epithelioid, occasionally short spindled cells with delicate intratumoral vasculature and frequent myxoid stroma. Mitotic activity ranged from 0 to 8 mitoses/2 mm2 (mean 2). Lymphovascular invasion/protrusion of tumor cells into endothelial-lined vascular spaces was present or suspected in 6 cases. Necrosis, significant nuclear pleomorphism, or well-developed, fascicular spindle-cell growth were absent. Half demonstrated features of the newly proposed subset, "distinctive nested glomoid neoplasm." Tumors were consistently positive for CD56 (n = 5/5). A subset was stained with S100 protein (n = 7/13), SMA (n = 6/13), keratin (n = 2/9), EMA (n = 3/7), and CD99 (n = 2/6). Tumors harbored ACTB::GLI1 (n = 15) or PTCH1::GLI1 (n = 1) fusions. The assays used did not capture cases defined by GLI1 amplification. We also identified recurrent cytogenetic gains (1q, 5, 7, 8, 12, 12q13.2-ter, 21, and X). For patients with available clinical follow-up (n = 8), half were disease free. Half demonstrated distant metastases (lungs, bone, or soft tissue). Of cases without follow-up (n = 8), 2 were known recurrences, and 1 was presumed metastasis. Our results imply a more aggressive biological potential than currently reported. Given the possibility for metastasis and disease progression, even in cytologically bland, nested tumors, close clinical surveillance, akin to that for sarcoma management, may be indicated. The term GLI1-altered mesenchymal tumor with malignant potential is proposed.
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Neoplasias de Tecido Conjuntivo e de Tecidos Moles , Sarcoma , Neoplasias de Tecidos Moles , Adulto , Humanos , Proteína GLI1 em Dedos de Zinco/genética , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/patologia , Proteínas S100 , Sarcoma/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análiseRESUMO
BACKGROUND: Atypical intradermal smooth muscle neoplasm, also commonly termed cutaneous leiomyosarcoma, is a soft tissue tumor with a low risk of aggressive behavior. These lesions arise in the dermis with possible superficial subcutaneous extension, demonstrate cytologic atypia, and often show mitotic activity. METHODS: A retrospective review of patient demographics, tumor characteristics, and treatment methods was conducted in a consecutive series of patients presenting to MD Anderson Cancer Center (MDACC) from 2002 to 2021 (n = 95). All pathology was reviewed by MDACC pathologists and determined to be atypical intradermal smooth muscle neoplasm. RESULTS: Median age at diagnosis was 58 years (range 22-86), and 74% were male. Ninety-five percent (n = 90) of patients identified as White, non-Hispanic. Most tumors were slow-growing, solitary, and painless nodules. Tumors were in the lower extremities (44.2%), followed by the upper extremity (28.4%), trunk (22.1%), and head and neck (5.2%). All patients (n = 44, 46.3%) who had a punch/incisional biopsy for diagnostic purposes had a subsequent tumor excision. Unplanned excision or excisional biopsy was performed on the remaining 46 (48%) patients. Of this subset, 41 of the 46 aforementioned patients (89%) had positive margins and underwent re-excision. Final pathology in 25/38 (66%) re-excision specimens was negative for residual tumor despite an initial positive margin. Two patients in the cohort had local recurrence 2 and 3 years after initial surgery. Both patients had positive margins, underwent excision of the recurrent tumor, and remain free of disease. After median follow-up of 6.9 years (range 1 day-18 years), 5-year recurrence-free survival was 96% and overall survival (OS) of the entire cohort was 78%. CONCLUSION: In this study of consecutive patients presenting with atypical intradermal smooth muscle neoplasm, we found good OS and local control after definitive surgical excision with negative margins, including excisional biopsy with close margins. Atypical intradermal smooth muscle neoplasm is unlikely to metastasize and has an excellent prognosis. Guidelines to determine optimal surveillance strategies for these patients should be revisited.
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AIMS: Glomus tumours are neoplasms with perivascular smooth muscle differentiation, which rarely occur in the oesophagus and may behave aggressively in this site based upon prior case reports. This study describes the clinicopathologic features of three oesophageal glomus tumours diagnosed at two large academic institutions between 1984 and 2022. METHODS AND RESULTS: Three cases of oesophageal glomus tumours were identified. Patients included two females and one male, with an age range of 19-65 years. All three tumours behaved in a malignant fashion, with metastases to various sites (lymph nodes, lung, pericardium, pleura, diaphragm, scalp). One patient developed an aorto-oesophageal fistula, resulting in a fatal haemorrhage. Tumours ranged in size from 4.5 to 8.1 cm. Histologically, all tumours had a multinodular, perivascular growth pattern. The neoplasms showed varying degrees of cytologic atypia and spindling, elevated mitotic activity (2-12 mitotic figures per 10 high-power fields), and necrosis was seen in in two cases. All tumours expressed smooth muscle actin by immunohistochemistry, and harboured NOTCH gene alterations (MIR143::NOTCH2 fusion in two cases; NOTCH3 rearrangement and NOTCH1 point mutation in one case). An ATRX splicing mutation in exon 10 was also identified in one case. CONCLUSION: Oesophageal glomus tumours pose diagnostic challenges, given their rarity at this site, but can be recognised by their characteristic perivascular growth pattern, round central nuclei, and supportive ancillary studies. Given the propensity for aggressive behaviour in this location, we recommend management by a multidisciplinary sarcoma team for optimal outcome.
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Neoplasias Esofágicas , Tumor Glômico , Neoplasias de Tecidos Moles , Feminino , Humanos , Masculino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Tumor Glômico/genética , Tumor Glômico/patologia , Neoplasias de Tecidos Moles/patologia , Pulmão/patologiaRESUMO
AIMS: NUTM1-rearranged sarcoma is an emerging entity that differs from NUT carcinoma at the molecular level, with most of the former tumours harbouring fusions involving genes in the MYC-associated factor X dimerization (MAD) transcription family (MXD1, MXD4, MXI1 [or MXD2], and MGA). MGA::NUTM1 is one of the most recently described novel gene fusions associated with NUTM1-rearranged sarcoma. Herein we describe the clinicopathologic features of three sarcomas with an MGA::NUTM1 fusion. METHODS AND RESULTS: The three study patients were male, with an age range of 10-28 years. The tumour sites were deep soft tissue of the thigh, the chest wall, and the pelvis. All three tumours were aggressive, with multiple recurrences and metastases. Histologically, the tumours were composed of monotonous spindle, round, or epithelioid cells in variably hyalinized stroma and prominent aggregates of amianthoid fibre-like collagen or collagen rosettes. Mitotic activity was relatively low (5-12 mitotic figures per 10 hhpf). All tumours tested expressed NUT, with one tumour having S100 protein expression and two tumours having CD99 and CD56 expression. The genetic breakpoints were MGA exon 21, MGA exon 22, and NUTM1 exon 3. CONCLUSION: MGA::NUTM1 sarcoma often exhibits hyalinized stroma with amianthoid fibre-like collagen or collagen rosettes in the presence of monotonous round, epithelioid, or spindle cell morphology. NUT immunohistochemistry and molecular testing can help confirm the diagnosis.
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Sarcoma , Neoplasias de Tecidos Moles , Humanos , Masculino , Criança , Adolescente , Adulto Jovem , Adulto , Feminino , Proteínas de Neoplasias/genética , Fatores de Transcrição/genética , Sarcoma/genética , Sarcoma/patologia , Fusão Gênica , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/patologia , Colágeno , Proteínas de Fusão Oncogênica/genética , Proteínas Repressoras/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genéticaRESUMO
BACKGROUND AND OBJECTIVES: Distinguishing sarcomatoid carcinoma from primary sarcoma is clinically important. We sought to characterize metastatic sarcomatoid bone disease and its management. METHODS: We analyzed the characteristics of all cases of sarcomatoid carcinoma to bone at a single institution from 2001 to 2021, excluding patients with nonosseous metastases. Survival was evaluated using the Kaplan-Meier method. RESULTS: We identified 15 cases of metastatic sarcomatoid carcinoma to bone. In seven cases the primary cancer was unknown at presentation. Renal cell carcinoma was suspected or confirmed in nine cases. Nine patients presented with pathologic fracture and two with concomitant visceral metastases. All patients underwent image-guided core needle or open biopsy. Ten required surgery for discrete osseous metastases; in four cases definitive surgery was delayed (median delay, 19 days) due to inability to rule out sarcoma with frozen section. No patients required reoperation or had construct failure. Thirteen died of disease; median survival was 17.5 months (interquartile range, 6.2-25.1). CONCLUSIONS: Metastatic sarcomatoid carcinoma is a clinically challenging entity. Multidisciplinary input and communication are key to identifying the primary carcinoma, locating osseous metastases, and defining an operative fixation that will survive the remainder of the patient's life.
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Neoplasias Ósseas , Carcinoma de Células Renais , Neoplasias Renais , Sarcoma , Humanos , Neoplasias Renais/patologia , Carcinoma de Células Renais/patologia , Sarcoma/patologia , Biópsia , Neoplasias Ósseas/cirurgiaRESUMO
BACKGROUND: Solitary fibrous tumour (SFT) is a unique mesenchymal neoplasm with classic features on histology and is characterised by the NAB2-STAT6 gene fusion. There are rare reports of SFTs with pancreatic involvement and only two cases in the literature reporting its features by preoperative fine needle aspiration (FNA). Herein, we characterise the cytomorphological features of four SFTs involving the pancreas by FNA to establish a preoperative diagnostic approach. METHODS: The anatomic pathology archives of two academic medical centres were searched to identify patients with a pancreatic FNA cytology specimen and a confirmed diagnosis of SFT by surgical resection. The clinical history, pathological diagnosis, cytomorphological findings, and results of immunohistochemistry (IHC) were reviewed. RESULTS: Four SFTs were identified from four patients with a median age of 59 years. The morphological features were variable but most frequently showed a bland spindled-to-epithelioid proliferation in fragments and single cells with small, oval, elongated, and hypochromatic nuclei in a haphazard arrangement with or without dense collagen. One tumour presented with a concurrent metastasis and showed a pure epithelioid component with necrosis and enlarged, hyperchromatic nuclei with conspicuous nucleoli and scattered mitoses. IHC was necessary for all diagnoses which were confirmed by surgical resection. CONCLUSIONS: SFTs with pancreatic involvement are rare, and non-specific features and tumour heterogeneity can pose a diagnostic challenge on FNA; however, IHC can be used to make a definitive diagnosis. As a result, FNA is a simple, safe, cost-effective, and accurate approach that can be used to diagnose SFT in the pancreas.
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Tumores Fibrosos Solitários , Biópsia por Agulha Fina/métodos , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Pâncreas/patologia , Tumores Fibrosos Solitários/diagnóstico , Tumores Fibrosos Solitários/patologiaRESUMO
There are no effective treatments for leiomyosarcoma (LMS) spreading intraabdominally. The aim of this study was to develop precision chemotherapy for recurrent peritoneal LMS metastases in a patient-derived orthotopic xenograft (PDOX) model. The LMS PDOX models were established orthotopically on the dome of the bladder of nude mice. The LMS PDOX models were randomized into 6 groups when the tumor volume reached 80â¯mm3: G1: untreated control; G2: doxorubicin (DOX) (DOX: i.p., 3â¯mg/kg, weekly, 3 weeks); G3: DOX combined with olaratumab (OLA) (DOX: i.p., 3â¯mg/kg, weekly, 3 weeks; OLA: i.p., 40â¯mg/kg, 3 times/week, 3 weeks); G4: gemcitabine (GEM) combined with docetaxel (DOC) (GEM: i.p., 100⯠mg/kg, weekly, 3 weeks; DOC: i.p., 20⯠mg/kg, weekly, 3 weeks); G5: pazopanib (PAZ) (PAZ: p.o., 100⯠mg/kg, daily, 3 weeks); G6: palbociclib (PAL) (PAL: p.o., 100⯠mg/kg, daily, 3 weeks). All mice were sacrificed on day 22. Body weight was assessed twice a week. Tumor volume was measured on day 0 and day 22. Although all regimens had a significant efficacy compared to the untreated group (Pâ¯<â¯0.001), only GEM combined with DOC regressed the tumor significantly (Pâ¯<â¯0.001), suggesting GEM combined with DOC has clinical potential for this LMS patient.
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Desoxicitidina/análogos & derivados , Docetaxel/uso terapêutico , Leiomiossarcoma/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Desoxicitidina/uso terapêutico , Xenoenxertos , Humanos , Leiomiossarcoma/patologia , Camundongos , Camundongos Nus , Metástase Neoplásica/prevenção & controle , Neoplasias Peritoneais/patologia , Recidiva , Terapia de Salvação/métodos , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacos , GencitabinaRESUMO
Myxofibrosarcoma (MFS) is the most common sarcomas in elderly patients and is either chemo-resistant or recurs with metastasis after chemotherapy. This recalcitrant cancer in need of improved treatment. We have established a patient-derived orthotopic xenograft (PDOX) of MFS. The MFS PDOX model was established in the biceps femoris of nude mice and randomized into 7 groups of 7 mice each: control; doxorubicin (DOX); pazopanib (PAZ); temozolomide (TEM); Irinotecan (IRN); IRN combined with TEM; IRN combined with cisplatinum (CDDP) and Salmonella typhimurium A1-R (S. typhimurium A1-R). Treatment was evaluated by relative tumor volume and relative body weight. The MFS PDOX models were DOX, PAZ, and TEM resistant. IRN combined with TEM and IRN combined with CDDP were most effective on the MFS PDOX. S. typhimurium A1-R arrested the MFS PDOX tumor. There was no significant body weight loss in any group. The present study suggests that the combination of IRN with either TEM or CDDP, and S. typhimurium have clinical potential for MFS.
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Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Fibrossarcoma/tratamento farmacológico , Infecções por Salmonella/tratamento farmacológico , Ensaios Antitumorais Modelo de Xenoenxerto , Animais , Cisplatino/administração & dosagem , Doxorrubicina/administração & dosagem , Fibrossarcoma/microbiologia , Humanos , Indazóis , Irinotecano/administração & dosagem , Masculino , Camundongos Nus , Pirimidinas/administração & dosagem , Distribuição Aleatória , Infecções por Salmonella/microbiologia , Salmonella typhimurium/fisiologia , Sulfonamidas/administração & dosagem , Temozolomida/administração & dosagem , Carga Tumoral/efeitos dos fármacosRESUMO
Melanoma is a recalcitrant cancer. To improve and individualize treatment for this disease, we previously developed a patient-derived orthotopic xenograft (PDOX) model for melanoma. We previously reported the individual efficacy of tumor-targeting Salmonella typhimurium A1-R (S. typhimurium A1-R) and recombinant methioninase (rMETase) for melanoma in the PDOX models of this disease. In the present study, we evaluated the efficacy of the combination of S. typhimurium A1-R with orally-administered rMETase (o-rMETase) for BRAF-V600E-negative melanoma in a PDOX model. Three weeks after implantation, 60 PDOX mouse models were randomized into six groups of 10 mice each: untreated control, temozolomide (TEM); o-rMETase; S. typhimurium A1-R; TEM + rMETase, S. typhimurium A1-R + rMETase. All treatments inhibited tumor growth compared to untreated control (TEM: p < 0.0001, rMETase: p < 0.0001, S. typhimurium A1-R: p < 0.0001, TEM + rMETase: p < 0.0001, S. typhimurium A1-R + rMETase: p < 0.0001). The most effective was the combination of S. typhimurium A1-R + o-rMETase which regressed this melanoma PDOX, thereby indicating a new paradigm for treatment of metastatic melanoma.
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Antineoplásicos/uso terapêutico , Liases de Carbono-Enxofre/uso terapêutico , Melanoma/terapia , Pseudomonas putida/enzimologia , Salmonella typhimurium , Temozolomida/uso terapêutico , Administração Oral , Animais , Antimetabólitos Antineoplásicos/uso terapêutico , Antineoplásicos/administração & dosagem , Liases de Carbono-Enxofre/administração & dosagem , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos , Humanos , Masculino , Melanoma/genética , Melanoma/microbiologia , Melanoma/patologia , Camundongos Nus , Mutação Puntual , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêutico , Salmonella typhimurium/fisiologia , Temozolomida/administração & dosagemRESUMO
BACKGROUND: Ewing's sarcoma (ES) is a recalcitrant disease in need of transformative therapeutics. OBJECTIVES: The aim of this study was to investigate the efficacy of tumor-selective Salmonella typhimurium A1-R combined with tumor metabolism targeting with oral administration of recombinant methioninase (o-rMETase), on an ES patient-derived orthotopic xenograft (PDOX) model. METHODS: The ES PDOX models were previously established in the right chest wall. The ES PDOX models were randomized into 5 groups when the tumor volume reached 80 mm3: G1: untreated control; G2: doxorubicin; G3: S. typhimurium A1-R; G4: o-rMETase; G5: S. typhimurium A1-R combined with o-rMETase. All mice were sacrificed on day 15. Body weight and tumor volume were assessed twice a week. RESULTS: S. typhimurium A1-R and o-rMETase respectively suppressed tumor growth as monotherapies (p = 0.050 and p = 0.032). S. typhimurium A1-R combined with o-rMETase regressed tumor growth significantly compared to untreated group on day 15 (p < 0.032). S. typhimurium A1-R combined with o-rMETase group was significantly more effective than S. typhimurium A1-R or o-rMETase monotherapy (p = 0.032, p = 0.032). CONCLUSIONS: The present results suggest that the combination of S. typhimurium A1-R and o-rMETase has promise to be a transformative therapy for ES.
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Neoplasias Ósseas/tratamento farmacológico , Liases de Carbono-Enxofre/uso terapêutico , Salmonella typhimurium/patogenicidade , Sarcoma de Ewing/tratamento farmacológico , Administração Oral , Animais , Antibióticos Antineoplásicos/uso terapêutico , Peso Corporal , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Liases de Carbono-Enxofre/genética , Liases de Carbono-Enxofre/metabolismo , Modelos Animais de Doenças , Doxorrubicina/uso terapêutico , Feminino , Humanos , Camundongos , Camundongos Nus , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/uso terapêutico , Sarcoma de Ewing/metabolismo , Sarcoma de Ewing/patologia , Transplante HeterólogoRESUMO
INTRODUCTION: In children and adolescents, most sarcoma subtypes have a simple karyotype with a single genetic alteration; cytologic findings combined with ancillary testing can lead to a specific diagnosis. The goal of this study was to review the use of fine-needle aspiration in conjunction with immunohistochemistry and molecular studies as a part of an integrated, multidisciplinary diagnostic workup for bone and soft tissue sarcomas in this population. MATERIALS AND METHODS: We searched for cases aged ≤18 years old with a malignant bone or soft tissue tumor that had corresponding cytology specimens from 3 institutions. Clinical data, cytologic findings and diagnoses, histologic diagnoses, and ancillary testing were documented. RESULTS: Of 99 cases, 55% were male with a mean age of 12 years. Ninety-four cases (95%) had a specific histologic diagnosis, and 84 cases (85%) were primary neoplasms. Ninety-four cases (95%) had a malignant cytologic diagnosis, and 71 cases (72%) had a specific cytologic diagnosis concordant with the histologic diagnosis. Among primary tumors with a specific histologic diagnosis, a specific cytologic diagnosis was made in 63 cases (79%). After excluding osteosarcoma, 74% of the tumors (n = 50) had molecular studies. Specific genetic alterations supporting a definitive diagnosis were found in 42 cases (84%), the majority of which were demonstrated using Fluorescence In Situ Hybridization (n = 33, 79%). CONCLUSIONS: We found that fine-needle aspiration in conjunction with core needle biopsy, immunohistochemistry, and molecular studies allowed cytopathologists to accurately classify sarcomas in a pediatric age group.
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Neoplasias Ósseas , Sarcoma , Neoplasias de Tecidos Moles , Adolescente , Criança , Feminino , Humanos , Masculino , Biópsia por Agulha Fina , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Citologia , Hibridização in Situ Fluorescente , Sarcoma/diagnóstico , Sarcoma/genética , Sarcoma/patologia , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/patologiaRESUMO
Dermatofibrosarcoma protuberans (DFSP) is a dermal malignant mesenchymal tumor. Most variants are associated with a high risk of local recurrence and a low risk of metastasis. The classic histomorphology of this tumor is made up of uniform, spindle-shaped cells, arranged in a storiform pattern. Tumor cells characteristically infiltrate the underlying subcutis in a honeycomb pattern. Less common variants of DFSP have been identified: myxoid, pigmented, myoid, granular cell, sclerosing, atrophic, and fibrosarcomatous. Only the fibrosarcomatous variant has been shown to differ significantly from classic DFSP in terms of clinical outcome; fibrosarcomatous DFSP has been shown to be associated with a greater risk of local recurrence and metastatic potential than classic DFSP. However, the other variants may pose diagnostic difficulty as they resemble other types of spindle cell neoplasms, especially in small biopsy specimens. This article reviews the clinical, histologic, and molecular features of DFSP variants, as well as possible pitfalls in their diagnosis and how to resolve them.
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A subset of clear cell chondrosarcomas may contain focal areas of low-grade conventional chondrosarcoma; however, it is rare to find foci resembling clear cell chondrosarcoma admixed with areas otherwise typical conventional chondrosarcoma. We report two patients with conventional chondrosarcoma with clear cell features occurring in the rib, one in the setting of multiple hereditary exostoses (MHE) and the other without MHE. Both patients were found to have a destructive rib mass with a soft tissue component and underwent en bloc resection. Histologic examination revealed predominantly grade 2 conventional chondrosarcomas; however, multiple foci containing large cells with pale eosinophilic to clear cytoplasm, distinct cell borders, centrally located nuclei, and conspicuous nucleoli, resembling clear cell chondrosarcoma were identified throughout the specimen. The significance of clear cell features in an otherwise typical conventional chondrosarcoma, to our knowledge, is unknown and deserves recognition. Finally, these tumors highlight the need for careful histologic examination and proper classification as unexpected findings may impact management.
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Neoplasias Ósseas , Condrossarcoma de Células Claras , Condrossarcoma , Humanos , Condrossarcoma/diagnóstico , Condrossarcoma/cirurgia , Condrossarcoma/patologia , Núcleo Celular/patologia , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/cirurgia , Neoplasias Ósseas/patologia , Costelas/cirurgia , Costelas/patologiaRESUMO
Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a rare and highly aggressive malignant neoplasm characterized by high-grade undifferentiated morphologic features and recurrent inactivating mutations of SMARCA4. These tumors consistently exhibit loss of SMARCA4 (BRG1) while displaying variable expression of other nonspecific markers. Recently, we encountered a SMARCA4-UT demonstrating immunoreactivity for GATA3, and we sought to characterize this phenomenon in a larger series.A total of nine SMARCA4-UTs were examined from 3 large academic institutions. The clinicopathologic and molecular characteristics were studied and GATA3 immunohistochemistry was performed.The cohort included 5 male and 4 female patients, with a median age of 54 years and a median smoking history of 37 pack-years. At initial diagnosis, mediastinal lymph node involvement was observed in 5 patients (56%) while distant metastases were present in 7 patients (78%). The median survival was 6 months. Histologically, the tumors were characterized by sheets of undifferentiated epithelioid and/or rhabdoid cells, accompanied by frequent mitotic figures and necrosis. Immunohistochemically, all tumors displayed a complete loss of BRG1 expression. Notably, 4 of 9 tumors (44%) were positive for GATA3 expression, including one tumor that exhibited strong and diffuse immunoreactivity.GATA3 expression in SMARCA4-UT may pose diagnostic challenges, requiring differentiation from other GATA3-positive tumors. This distinction is crucial for accurate prognostication and treatment decisions.
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AIMS: Cutaneous syncytial myoepithelioma (CSM) is a rare myoepithelioma variant of skin, characterized by intradermal syncytial growth of spindle cells with a distinct immunophenotype of EMA and S100 positivity and infrequent keratin expression. While CSM was first described as a cutaneous tumor, singular non-cutaneous cases have since been reported in bone. We aimed to investigate the clinicopathological features of this variant across all anatomic sites through a large multi-institutional study. METHODS AND RESULTS: We complied a total of 24 myoepitheliomas with syncytial growth from our files. The tumors occurred in 12 male and 12 female patients (M:F = 1:1), with a median age of 31 years (range, 9-69 years). While the majority of tumors (75%, n = 18) occurred in skin, a significant subset (25%, n = 6) arose in non-cutaneous sites, including bone (n = 3), bronchus/trachea (n = 2), and interosseous membrane of tibia/fibula (n = 1). Tumor size ranged from 0.4 to 5.9 cm. Clinical follow-up (7 patients; range 14-202 months; median 56.5 months) showed a single local recurrence 8 years after incomplete skin excision but no metastases; all patients were alive at the time of last follow-up without evidence of disease. Histologically, all tumors were pink at low-power and characterized by a syncytial growth of bland ovoid, spindled, or histiocytoid cells with eosinophilic cytoplasm and prominent perivascular lymphoplasmacytic inflammation. One-third displayed adipocytic metaplasia (8/24). Rare cytologic atypia was seen but was not associated with increased mitotic activity. All tumors expressed S100, SMA, and/or EMA. Keratin expression was absent in most cases. Molecular analysis was performed in 16 cases, all showing EWSR1-rearrangments. In total, 15/15 (100%) harbored an EWSR1::PBX3 fusion, whereas 1 case EWSR1 FISH was the only molecular study performed. CONCLUSION: Syncytial myoepithelioma is a rare but recognizable morphologic variant of myoepithelioma which may have a predilection for skin but also occurs in diverse non-cutaneous sites. Our series provides evidence supporting a reappraisal of the term "cutaneous syncytial myoepithelioma," as 25% of patients in our series presented with non-cutaneous tumors; thus, we propose the term "syncytial myoepithelioma" to aid pathologist recognition and avoidance of potentially confusing terminology when referring to non-cutaneous examples. The behavior of syncytial myoepithelioma, whether it arises in cutaneous or non-cutaneous sites, is indolent and perhaps benign with a small capacity for local recurrence.
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Mioepitelioma , Neoplasias Epiteliais e Glandulares , Neoplasias Cutâneas , Humanos , Masculino , Feminino , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Mioepitelioma/patologia , Biomarcadores Tumorais/análise , Neoplasias Cutâneas/patologia , QueratinasRESUMO
Pericytes are multipotent mesenchymal precursor cells that demonstrate tissue-specific properties. In this study, by comparing human adipose tissue- and periosteum-derived pericyte microarrays, we identified T cell lymphoma invasion and metastasis 1 (TIAM1) as a key regulator of cell morphology and differentiation decisions. TIAM1 represented a tissue-specific determinant between predispositions for adipocytic versus osteoblastic differentiation in human adipose tissue-derived pericytes. TIAM1 overexpression promoted an adipogenic phenotype, whereas its downregulation amplified osteogenic differentiation. These results were replicated in vivo, in which TIAM1 misexpression altered bone or adipose tissue generation in an intramuscular xenograft animal model. Changes in pericyte differentiation potential induced by TIAM1 misexpression correlated with actin organization and altered cytoskeletal morphology. Small molecule inhibitors of either small GTPase Rac1 or RhoA/ROCK signaling reversed TIAM1-induced morphology and differentiation in pericytes. In summary, our results demonstrate that TIAM1 regulates the cellular morphology and differentiation potential of human pericytes, representing a molecular switch between osteogenic and adipogenic cell fates.
Assuntos
Actinas , Pericitos , Animais , Humanos , Fatores de Troca do Nucleotídeo Guanina/genética , Osteogênese , Diferenciação Celular , Tecido Adiposo , Proteína 1 Indutora de Invasão e Metástase de Linfoma de Células TRESUMO
The term "Atypia" has been employed to describe a wide spectrum of cytomorphologic features associated with reactive/inflammatory processes as well as those suspicious for neoplasms in cytology. Similar to other cytopathology reporting systems, the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) has reserved the atypical category for cytology specimens lacking quantitative and/or qualitative cytomorphologic features to be diagnosed with confidence as either non-neoplastic or neoplastic. In MSRSGC, the atypical category is associated with a risk of malignancy and recommendation for clinical management. In this review, we discuss the value of atypical diagnostic category of MSRSGC in both cystic and non-cystic salivary gland lesions by evaluating our institutional case cohort.
Assuntos
Neoplasias das Glândulas Salivares , Biópsia por Agulha Fina , Citodiagnóstico , Técnicas Citológicas , Humanos , Estudos Retrospectivos , Neoplasias das Glândulas Salivares/diagnóstico , Neoplasias das Glândulas Salivares/patologia , Glândulas Salivares/patologiaRESUMO
BACKGROUND: Pleomorphic liposarcoma (PLPS) is the least common but most aggressive of all forms of liposarcoma (LPS). Its diagnosis relies on the recognition of pleomorphic lipoblasts (PLBs), whose numbers vary considerably. Because few large fine-needle aspiration (FNA) biopsy studies exist, the authors review their experience with PLPS. METHODS: The authors' cytopathology files were searched for PLPS with histopathologic verification. FNA biopsy smears were performed via standard techniques. RESULTS: Twenty cases from 20 patients (male/female ratio, 2.3/1; age range, 22-77 years; mean age, 58 years) met the inclusion criteria. All had tissue confirmation. Biopsy sites included the following: thigh (11 [55%]), upper extremity (4 [20%]), axilla (2 [10%]), neck (1 [5%]), chest wall (1 [5%]), and mediastinum (1 [5%]). Aspirates were from primary (17 [85%]), locally recurrent (2 [10%]), and metastatic neoplasms (1 [5%]). The FNA diagnoses were PLPS (10 [50%]), myxofibrosarcoma (4 [20%]), LPS (2 [10%]), sarcoma (2 [10%]), and high-grade malignant neoplasm (2 [10%]). Smears showed thick cell clusters and dissociated single forms. Pleomorphic, epithelioid, and bizarre cell/nuclear shapes were common. PLBs were absent, rare, or unnoticed in 45%. In 25%, smears dominated by myxoid stroma were diagnosed as high-grade myxofibrosarcoma or myxoid LPS. Ancillary testing performed in 5 cases had limited diagnostic efficacy. CONCLUSIONS: FNA biopsy of PLPS, although able to successfully recognize malignancy, suffers from a sampling bias due to an inability to capture or recognize PLBs in a significant proportion of cases secondary to the heterogeneous composition of this neoplasm.
Assuntos
Lipossarcoma , Sarcoma , Neoplasias de Tecidos Moles , Adulto , Idoso , Biópsia por Agulha Fina , Feminino , Humanos , Lipopolissacarídeos , Lipossarcoma/diagnóstico , Lipossarcoma/patologia , Lipossarcoma/secundário , Masculino , Pessoa de Meia-Idade , Neoplasias de Tecidos Moles/patologia , Adulto JovemRESUMO
Annotating cancerous regions in whole-slide images (WSIs) of pathology samples plays a critical role in clinical diagnosis, biomedical research, and machine learning algorithms development. However, generating exhaustive and accurate annotations is labor-intensive, challenging, and costly. Drawing only coarse and approximate annotations is a much easier task, less costly, and it alleviates pathologists' workload. In this paper, we study the problem of refining these approximate annotations in digital pathology to obtain more accurate ones. Some previous works have explored obtaining machine learning models from these inaccurate annotations, but few of them tackle the refinement problem where the mislabeled regions should be explicitly identified and corrected, and all of them require a - often very large - number of training samples. We present a method, named Label Cleaning Multiple Instance Learning (LC-MIL), to refine coarse annotations on a single WSI without the need for external training data. Patches cropped from a WSI with inaccurate labels are processed jointly within a multiple instance learning framework, mitigating their impact on the predictive model and refining the segmentation. Our experiments on a heterogeneous WSI set with breast cancer lymph node metastasis, liver cancer, and colorectal cancer samples show that LC-MIL significantly refines the coarse annotations, outperforming state-of-the-art alternatives, even while learning from a single slide. Moreover, we demonstrate how real annotations drawn by pathologists can be efficiently refined and improved by the proposed approach. All these results demonstrate that LC-MIL is a promising, lightweight tool to provide fine-grained annotations from coarsely annotated pathology sets.