Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 277
Filtrar
1.
Acta Chir Orthop Traumatol Cech ; 89(3): 220-223, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35815490

RESUMO

Given the low incidence of musculoskeletal tumors during pregnancy, publications on the subject are scarce and treatment guidelines nonexistent. We present five cases of musculoskeletal tumors in pregnant women, three with metastasizing malignant neoplasms and two with aggressive giant cell tumors. The three patients diagnosed during their gestational period were operated before the end of pregnancy, adapting surgical techniques to minimize risk to mother and fetus. Adjuvant therapies were postponed until the end of gestation. All newborns were delivered at term vaginally, except for one where a cesarean section was required. After a mean follow-up of 69.96 months (±56.38), all patients were free of disease, except for the one diagnosed with an extraskeletal myxoid chondrosarcoma who died at 4 years from diagnosis. Surgery plays a key role in the treatment of musculoskeletal tumors diagnosed during pregnancy. These patients must be treated by multidisciplinary teams at sarcoma reference hospitals, involving the obstetrics team in the decision-making process, and adapting each step of the diagnosis and treatment to the gestational period. Key words: pregnancy, musculoskeletal tumors, sarcoma, cancer, oncological surgery.


Assuntos
Condrossarcoma , Neoplasias de Tecido Conjuntivo e de Tecidos Moles , Sarcoma , Cesárea , Extremidades , Feminino , Humanos , Recém-Nascido , Gravidez
2.
Pathologica ; 114(3): 228-237, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35775709

RESUMO

Primary extraskeletal myxoid chondrosarcoma (pEMC) of the breast is rare and only a few cases have been reported to date. Herein, we report a case of primary EMC of the breast in a 45-year-old female. The patient presented with a left breast mass for 1 month. Mammogram revealed a fairly circumscribed mass with spicules of calcifications. The core biopsy and resection specimen showed a myxoid soft tissue neoplasm with histologic features of a myxoid chondrosarcoma. Necrosis, hemorrhage, and brisk mitotic activity were present. No malignant epithelial element was identified even after extensive sampling. The tumor cells exhibited immunoreactivity for vimentin, S100, neuron specific enolase, CD99, and synaptophysin, while the epithelial, myoepithelial, and mammary lineage-associated markers were negative. As up to 81% of EMC cases harbor t(9;22)(q22;q12), this results in a fusion of EWS RNA-binding protein 1 gene (EWSR1) at 22q12 to the nuclear receptor subfamily 4, group A, member 3 gene at 9q22. A rearrangement involving the EWSR1 locus was detected in our case. Whole body PET-CT did not reveal any other mass. A diagnosis of pEMC was rendered. The patient received six cycles of 5-Fluorouracil, Cyclophosphamide, and Adriamycin. The patient was in clinical and radiologic remission at the last follow-up (18 months post surgery). PET-CT and brain MRI were negative. In conclusion, surgical pathologists should include EMC in their differential while dealing with a myxoid soft tissue lesion of the breast, particularly in the core needle biopsies. An expeditious diagnosis of EMC of the breast would allow the surgeon to carry out conservative breast surgery instead of more radical approaches taken in cases of other primary malignant mammary neoplasms.


Assuntos
Condrossarcoma , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Animais , Biópsia com Agulha de Grande Calibre , Mama , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias de Tecido Conjuntivo e de Tecidos Moles
3.
Sci Rep ; 12(1): 10634, 2022 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-35739267

RESUMO

Necrosis seen in histopathology Whole Slide Images is a major criterion that contributes towards scoring tumour grade which then determines treatment options. However conventional manual assessment suffers from inter-operator reproducibility impacting grading precision. To address this, automatic necrosis detection using AI may be used to assess necrosis for final scoring that contributes towards the final clinical grade. Using deep learning AI, we describe a novel approach for automating necrosis detection in Whole Slide Images, tested on a canine Soft Tissue Sarcoma (cSTS) data set consisting of canine Perivascular Wall Tumours (cPWTs). A patch-based deep learning approach was developed where different variations of training a DenseNet-161 Convolutional Neural Network architecture were investigated as well as a stacking ensemble. An optimised DenseNet-161 with post-processing produced a hold-out test F1-score of 0.708 demonstrating state-of-the-art performance. This represents a novel first-time automated necrosis detection method in the cSTS domain as well specifically in detecting necrosis in cPWTs demonstrating a significant step forward in reproducible and reliable necrosis assessment for improving the precision of tumour grading.


Assuntos
Aprendizado Profundo , Neoplasias de Tecido Conjuntivo e de Tecidos Moles , Animais , Cães , Necrose , Redes Neurais de Computação , Reprodutibilidade dos Testes
4.
Diagn Cytopathol ; 50(8): E223-E229, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35514197

RESUMO

Mesenchymal tumors harboring GLI1 gene fusions are a rare new entity that typically occur in the head and neck region of young to middle aged adults, with a particular predilection for the tongue. We report herein a case of epithelioid mesenchymal tumor with PTCH1-GLI1 gene fusion of the right submental region in an 82-year-old male never smoker. Ultrasound-guided fine needle aspiration (FNA) with concomitant core needle biopsy was performed. Cytology smears revealed a hypercellular, monotonous aspirate comprised of epithelioid to plasmacytoid cells with round regular nuclei and moderate amounts of cytoplasm. There were admixed granulomata. The patient underwent surgical resection with limited neck dissection and subsequent pathologic examination with performed next generation sequencing confirmed the presence of epithelioid mesenchymal tumor with PTCH1-GLI1 gene fusion. To our knowledge, this is the first reported example of a mesenchymal tumor harboring GLI1 gene fusion initially evaluated by FNA.


Assuntos
Fusão Gênica , Neoplasias de Tecido Conjuntivo e de Tecidos Moles , Adulto , Idoso de 80 Anos ou mais , Biópsia por Agulha Fina , Citodiagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Proteína GLI1 em Dedos de Zinco/genética
5.
Sci Rep ; 12(1): 9095, 2022 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-35641597

RESUMO

Magnetic Resonance (MR) Imaging-guided High Intensity focused Ultrasound (MRgHIFU) is a non-invasive, non-ionizing thermal ablation therapy that is particularly interesting for the palliative or curative treatment of musculoskeletal tumors. We introduce a new modular MRgHIFU device that allows the ultrasound transducer to be positioned precisely and interactively over the body part to be treated. A flexible, MR-compatible supporting structure allows free positioning of the transducer under MRI/optical fusion imaging guidance. The same structure can be rigidified using pneumatic depression, holding the transducer rigidly in place. Targeting accuracy was first evaluated in vitro. The average targeting error of the complete process was found to be equal to 5.4 ± 2.2 mm in terms of focus position, and 4.7° ± 2° in terms of transducer orientation. First-in-man feasibility is demonstrated on a patient suffering from important, uncontrolled pain from a bone metastasis located in the forearm. The 81 × 47 × 34 mm3 lesion was successfully treated using five successive positions of the transducer, under real-time monitoring by MR Thermometry. Significant pain palliation was observed 3 days after the intervention. The system described and characterized in this study is a particularly interesting modular, low-cost MRgHIFU device for musculoskeletal tumor therapy.


Assuntos
Ablação por Ultrassom Focalizado de Alta Intensidade , Neoplasias de Tecido Conjuntivo e de Tecidos Moles , Termometria , Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Humanos , Imageamento por Ressonância Magnética/métodos , Dor
6.
Diagn Pathol ; 17(1): 42, 2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35488288

RESUMO

BACKGROUND: Extraskeletal myxoid chondrosarcomas (EMCs) are solid tumors that have been genetically and biologically characterized. Only a few studies have discussed the role of the KIT gene or CD117 expression in EMCs, identified by immunohistochemical (IHC) staining. Herein, we present a novel case of cellular EMC exhibiting an EWSR1-NR4A3 fusion, KIT exon 13 mutations and strong diffuse expression of CD117. CASE PRESENTATION: A 69-year-old man presented with a fist-sized tumor on his left shoulder. CT revealed a tumor in the left thoracic and dorsal muscle space. The tumor was completely resected. Histologically, the tumor cells had a nodular structure and infiltrated the peripheral fat and muscle tissues. The tumor cells were uniform in size with round nuclei, well-defined nucleoli and eosinophilic cytoplasm. Immunohistochemically, the tumor cells were positive for CD117, vimentin, CD56 and NSE and focally expressed desmin; the cells were negative for myogenin, S-100, SYN, INSM1, CD34, STAT6, INI-1, Brachyury, ERG, TLE1, AE1/AE3, WT-1, CD99 and SMA. NGS revealed an EWSR1-NR4A3 fusion and KIT exon 13 mutations. The patient had no further treatment after surgery, and no recurrence or metastasis occurred during the ~ 10 month follow-up period. CONCLUSIONS: Molecular detection is an indispensable technique for diagnosing cellular EMCs. The KIT mutations noted in this case report may offer fresh insights into EMCs treatment options.


Assuntos
Condrossarcoma , Neoplasias de Tecido Conjuntivo e de Tecidos Moles , Idoso , Condrossarcoma/diagnóstico , Condrossarcoma/genética , Fusão Gênica , Humanos , Masculino , Mutação , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/genética , Proteínas Repressoras/genética
7.
Am J Surg Pathol ; 46(8): 1126-1136, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35426837

RESUMO

Uterine leiomyoma (UL) is a common benign neoplasm which can sometimes be difficult to differentiate from the uterine inflammatory myofibroblastic tumor (IMT) based on morphology alone. IMT is a myofibroblastic/fibroblastic neoplasm which has typically been considered to be rare in the uterus. Its clinical behavior is usually indolent although aggressive variants exist. The majority of IMTs harbor genomic rearrangement of anaplastic lymphoma kinase ( ALK ), while ALK fusion has not been thus far detected in ULs. We analyzed 2263 ULs of which 9 (0.4%) had tyrosine-kinase activation. Seven of the samples were ALK immunopositive: 6 had an ALK fusion gene and 1 overexpressed an ALK transcript skipping exons 2 to 3, Moreover, 1 sample had a RET , and 1 a PDGFRB fusion gene. While no recurrent somatic mutations were found, 1 patient had an ALK germline mutation. Seven tumors showed leiomyoma-like morphology, 1 tumor had slightly loose, and 1 fibrous growth pattern. Six tumors had mild to moderate lymphocyte infiltration, while no immune cell infiltration was detected in 3 cases. None of the tumors showed aggressive behavior. Except for strong ALK positivity (7/9 tumors) the protein expression profile of the tumors was identical to ULs and distinct from other mesenchymal uterine tumors. In gene expression level, these tumors and the known UL subclasses did not separate perfectly. However, vitamin C metabolism and epithelial-mesenchymal transition pathways were uniquely enriched in these lesions. The overall similarity of the analyzed tumors to UL raises the question whether an UL diagnosis would be more proper for a subset of uterine IMTs.


Assuntos
Granuloma de Células Plasmáticas , Leiomioma , Neoplasias de Tecido Conjuntivo e de Tecidos Moles , Neoplasias Uterinas , Feminino , Fusão Gênica , Granuloma de Células Plasmáticas/genética , Humanos , Leiomioma/genética , Proteínas Tirosina Quinases/genética , Neoplasias Uterinas/patologia
8.
Ann Diagn Pathol ; 58: 151937, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35344860

RESUMO

Superficial CD34-positive fibroblastic tumor (SCPFT) is a recently described rare mesenchymal tumor of borderline malignancy. It generally involves superficial soft tissue, with a predilection to the lower extremities. Microscopically this tumor is characterized by a fascicular and storiform growth pattern, spindled to epithelioid cells, nuclear atypia with pleomorphism, and eosinophilic granular, and fibrillar to glassy cytoplasm. Strong diffuse immunoreactivity for CD34 is very characteristic of this entity. Due to under-recognition, this tumor is generally underreported. Additionally, cases of recurrence are rarely reported in the literature. We will comprehensively review the English language literature on all reported cases of SCPFT, with emphasis on recurrence.


Assuntos
Neoplasias de Tecido Conjuntivo e de Tecidos Moles , Neoplasias de Tecido Fibroso , Neoplasias de Tecidos Moles , Antígenos CD34 , Biomarcadores Tumorais , Células Epitelioides/patologia , Humanos , Neoplasias de Tecido Fibroso/patologia , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias de Tecidos Moles/patologia
9.
Mod Pathol ; 35(7): 911-921, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35149769

RESUMO

NTRK-rearranged mesenchymal neoplasms mostly affect the soft tissues of pediatric patients. Given the responsiveness to selective NTRK inhibitors, it remains critical to identify those ultra-rare cases occurring in the viscera of adults. In five females and two males aged 18-53 years, we characterized visceral mesenchymal tumors harboring TPM3-NTRK1 [uterine cervix (N = 2), pleura, prostate], LMNA-NTRK1 (lung), SQSTM1-NTRK3 (heart), and NTRK3 rearrangement with unknown fusion partner (colon/mesocolon) with RNA sequencing, FISH, RT-PCR, and immunohistochemistry. The tumors exhibited spindled to ovoid/epithelioid or pleomorphic cells, often arranged in fascicles, and were low-to-intermediate-grade and high-grade in three and four cases, respectively. Keloid-like stromal collagen and perivascular hyalinization was noted in five. Adenosarcoma-like appearances were observed in two, manifesting frond-like protrusions in one cervical tumor and phyllodes-like architecture in the prostatic tumor. Abrupt high-grade transformation into pleomorphic liposarcoma was found in another cervical tumor, while the pleural tumor contained intermixed rhabdomyoblasts. Pan-TRK immunostaining was positive in all cases. All cases expressed CD34, while five were S100-positive. CDKN2A homozygous deletion with concomitant p16 loss occurred in 4/7. Whole-exome sequencing identified TP53 mutation (c.672+2T>C, involving a splice site, with concomitant protein loss) in a cervical sarcoma, limited to its heterologous liposarcomatous component. At least moderate pan-TRK immunoreactivity was present in varying proportions of potential pathologic mimics, with BCOR-positive sarcoma (56%, 5/9), undifferentiated uterine sarcoma (50%, 3/6), and spindle cell/sclerosing rhabdomyosarcoma (33%, 2/6) being among the most frequent. This underscored the unsatisfactory specificity of pan-TRK immunohistochemistry and warranted molecular confirmation in the diagnosis of adult NTRK-rearranged visceral mesenchymal neoplasms. The current report highlights the ever-expanding clinicopathologic and genetic spectrum of this entity by describing the unprecedented cardiac and pleural locations and heterologous differentiation, as well as the second NTRK-rearranged "prostatic stromal sarcoma," while substantiating CDKN2A deletion as a frequent occurrence.


Assuntos
Neoplasias do Endométrio , Neoplasias de Tecido Conjuntivo e de Tecidos Moles , Sarcoma , Neoplasias de Tecidos Moles , Neoplasias do Colo do Útero , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Criança , Neoplasias do Endométrio/genética , Feminino , Rearranjo Gênico , Homozigoto , Humanos , Masculino , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/genética , Proteínas de Fusão Oncogênica/genética , Receptor trkA/análise , Receptor trkA/genética , Sarcoma/genética , Deleção de Sequência , Neoplasias de Tecidos Moles/genética , Neoplasias do Colo do Útero/genética , Vísceras/química , Vísceras/patologia
11.
Am J Surg Pathol ; 46(7): 1007-1013, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35220354

RESUMO

Three cases of primary NTRK-rearranged spindle cell neoplasm of the lung with resemblance to those described in the somatic soft tissues are presented. The patients are 2 males and 1 female with age at presentation ranging from 31 to 45 years (mean, 36 y). All the 3 tumors were discovered incidentally during physical examinations. None of the patients had any prior history of mesenchymal neoplasms anywhere else. Computed tomography revealed intrapulmonary mass located in the right upper lobe, left upper lobe, and left lower lobe, respectively. All the patients underwent lobectomy. Grossly, the tumors were described as yellowish-white solid measuring in size between 1.2 and 1.8 cm (mean, 1.5 cm). Histologically, they were characterized by monomorphic spindle cells arranged in haphazard fascicles accompanied by variable stromal collagens. Nuclear atypia was mild and mitotic activity was scarce. By immunohistochemistry, the neoplastic cells in all 3 cases showed strong and diffuse staining of CD34, pan-TRK, and TrkA with variable expression of S100 protein, whereas they were negative for cytokeratin, SOX10, ALK, α-smooth muscle actin, desmin, and STAT6. Fluorescence in situ hybridization analysis revealed NTRK1 rearrangement in all 3 cases. Subsequent next-generation sequencing identified TPM3-NTRK1 fusion in 2 cases and LMNA-NTRK1 fusion in 1 case. All 3 patients are alive without the disease (median follow-up, 9 mo; range, 4 to 87 mo). The cases present herein demonstrate that NTRK-rearranged spindle cell neoplasms may occur primarily in the lung, albeit extremely rare, and should be included in the differential diagnosis of primary pulmonary spindle cell neoplasms.


Assuntos
Neoplasias Pulmonares , Neoplasias de Tecido Conjuntivo e de Tecidos Moles , Adulto , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Pulmão/química , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/genética , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/patologia , Receptor trkA/genética
13.
Cancer Treat Res Commun ; 31: 100530, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35144048

RESUMO

INTRODUCTION: Extraskeletal myxoid chondrosarcoma is a rare form of soft tissue sarcoma characterized by a unique chromosomal translocation involving the NR4A3 gene on chromosome 9. It is most frequently diagnosed in the proximal extremities of older adult males and is notable for its insidious growth with predilection for local recurrence and metastasis. Currently, extraskeletal myxoid chondrosarcoma is managed with wide resection, with recent investigations supporting the utility of adjuvant radiation and novel chemotherapeutic strategies. METHODOLOGY: A retrospective study was performed with the Surveillance, Epidemiology, and End-Results (SEER) database, which was searched for cases of extraskeletal myxoid chondrosarcoma diagnosed between years 2004 and 2015. Demographic variables were assessed, as well as Collaborative Staging variables including tumor size, metastatic disease, grade, and lymph node involvement. Cases were stratified according to the anatomic site of the primary tumor and were described by therapeutic intervention. A multivariate Cox proportional hazards model evaluated predictive factors for poor survival, and Kaplan-Meier analyses assessed effects of various staging, demographic, and therapeutic variables on overall survival. RESULTS: There were 270 cases of extraskeletal myxoid chondrosarcoma reviewed in this study, which were diagnosed most frequently in the lower limb or hip of older adult males. The 5-year overall survival was 76.5% and was worse on univariate assessment for patients with age > 60, high histologic grade, pelvic location, tumor size > 8.0 cm, metastatic or nodal spread, and in patients without surgical intervention. The Cox regression predicted significantly worse survival for older age, larger tumor size, non-surgical status, and high tumor grade. Metastasis did not significantly predict worse survival on multivariate assessment, and neither chemotherapy nor radiotherapy provided a discernable improvement in survival in this cohort. DISCUSSION AND CONCLUSION: As a rare soft tissue sarcoma, many of the presenting features and survival outcomes of extraskeletal myxoid chondrosarcoma remain poorly defined due to the limited prevalence of this disease. The findings of this study suggest the overall survival may be worse than previously reported, and poor prognostic factors are those associated with worse survival in other soft tissue sarcomas, including high histologic grade, older age, larger tumor size, and lack of wide resection. Radiation and chemotherapy did not demonstrably improve survival for patients with localized or metastatic disease.


Assuntos
Condrossarcoma , Neoplasias de Tecido Conjuntivo e de Tecidos Moles , Sarcoma , Neoplasias de Tecidos Moles , Idoso , Condrossarcoma/diagnóstico , Condrossarcoma/genética , Condrossarcoma/patologia , Humanos , Masculino , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/genética , Estudos Retrospectivos , Sarcoma/diagnóstico , Sarcoma/patologia , Sarcoma/terapia , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/cirurgia
15.
Virchows Arch ; 480(5): 1107-1114, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34331570

RESUMO

BCOR-rearranged sarcomas are rare and belong to the Ewing-like sarcomas (ELS). Their morphology and histopathological features make the diagnosis challenging. We present a case, initially diagnosed as an unusual extraskeletal myxoid chondrosarcoma (EMC). A 54-year-old male patient developed an asymptomatic swelling of the lower leg. Imaging showed a 9.5-cm large intramuscular soft tissue mass. Due to its morphological and immunohistochemical profile on biopsy, it was initially diagnosed as an EMC. The patient was treated by complete resection and adjuvant radiotherapy and remained free of tumor at 7 years follow-up. Using next-generation sequencing (NGS), we retrospectively identified RGAG1-BCOR gene fusion (confirmed by RT-PCR), which has not been described in somatic soft tissue tumors so far. This finding broadens the spectrum of partner genes in the BCOR-rearranged sarcomas in a tumor with a well-documented, long clinical follow-up.


Assuntos
Neoplasias Ósseas , Sarcoma , Neoplasias de Tecidos Moles , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Neoplasias Ósseas/patologia , Condrossarcoma , Seguimentos , Fusão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias de Tecido Conjuntivo e de Tecidos Moles , Proteínas de Fusão Oncogênica/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Repressoras/genética , Estudos Retrospectivos , Sarcoma/patologia , Neoplasias de Tecidos Moles/genética
16.
Am J Clin Pathol ; 157(4): 485-493, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-34661642

RESUMO

OBJECTIVES: NTRK-rearranged spindle cell neoplasms (other than infantile fibrosarcoma) are an emerging entity of tumors that demonstrate wide variation in clinical and histopathologic features. We report a case of an NTRK-rearranged spindle cell neoplasm bearing a deceptively bland morphology. METHODS: We performed histopathologic, immunohistochemical, and molecular evaluation on resection tissue. We also conducted a literature review on adult NTRK3-rearranged spindle cell neoplasms. RESULTS: The tumor presented as a recurrent ankle mass in an elderly patient. Histologically, it was composed of bland spindle cells set in a fibrous to edematous stroma. Blood vessels were interspersed with subtle perivascular hyalinization and scattered lymphoid aggregates. Immunohistochemically, the spindle cells expressed CD34 and S100 while being negative for SOX10. The tumor also showed cytoplasmic reactivity for pan-tyrosine receptor kinase immunohistochemistry. Next-generation sequencing identified an NTRK3-SQSTM1 fusion. To the best of our knowledge, this fusion pair has not been previously reported in adult NTRK-rearranged mesenchymal tumors. CONCLUSIONS: Altogether, this rare and diagnostically challenging case of an NTRK3-rearranged spindle cell tumor with low-grade morphology is in contrast to many of the reported adult NTRK3-rearranged mesenchymal tumors. Recognition of low-grade NTRK-rearranged tumors demands close attention to clues in morphology and immunoprofiles.


Assuntos
Neoplasias de Tecido Conjuntivo e de Tecidos Moles , Receptor trkA , Adulto , Idoso , Biomarcadores Tumorais/genética , Rearranjo Gênico , Humanos , Imuno-Histoquímica , Proteínas de Fusão Oncogênica/genética , Receptor trkA/genética , Proteína Sequestossoma-1
17.
J Am Soc Cytopathol ; 11(1): 31-39, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34649776

RESUMO

INTRODUCTION: Soft tissue myoepithelioma (STM), a rare mesenchymal neoplasm morphologically analogous to its more common salivary gland (SG) counterpart, is the subject of single case reports regarding its fine-needle aspiration (FNA) biopsy. To our knowledge, ours is the first case series of STM. MATERIALS AND METHODS: A search was made of our pathology databases for cases diagnosed as STM. FNA biopsy smears and cell blocks were performed using standard techniques. RESULTS: Seven cases were retrieved from 4 men and 3 women (M:F = 1.3:1; age range: 25-79 years, x = 54 years). All but 1 presented as a primary neoplasm. Six aspirates were from the extremities, and 1 from the abdominal wall. Mean tumor size was 5.7 cm. Cytologic diagnosis of STM or suspicious for STM was made in 3 cases (43%). Remaining FNA diagnoses were spindle cell neoplasm/lesion (2), spindle cell sarcoma (1), and extraskeletal myxoid chondrosarcoma (1). Three cases were composed primarily or solely of uniform spindle cells, 3 primarily of uniform epithelioid cells with plasmacytoid features, and 1 case a mixture of these 2 cell types. Myxoid/chondromyxoid stroma was relatively abundant except in the single hypocellular example. Immunohistochemical (IHC) testing performed in 71% was nonspecific, but positive with S-100 in 4 of 5, EMA in 3 of 3, calponin in 2 of 2, and keratin in 1 of 3 examples. CONCLUSION: FNA biopsy smears of STM are remarkably similar cytomorphologically to their SG equivalent. However, STM can be misidentified principally as extraskeletal myxoid chondrosarcoma, thus requiring a relatively broad IHC panel for a specific diagnosis.


Assuntos
Biópsia por Agulha Fina/métodos , Mioepitelioma/patologia , Neoplasias de Tecidos Moles/patologia , Adulto , Idoso , Condrossarcoma/diagnóstico , Condrossarcoma/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mioepitelioma/diagnóstico , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/diagnóstico , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/patologia , Sarcoma/diagnóstico , Sarcoma/patologia , Neoplasias de Tecidos Moles/diagnóstico
18.
Virchows Arch ; 480(5): 1087-1099, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34779913

RESUMO

We report 10 additional cases of GLI1-altered mesenchymal tumor to further delineate its clinicopathological and molecular spectrum. There were seven males and three females with a median age of 31 years (range 1.3 ~ 75 years). Five tumors arose in the oral cavity, one each in the stomach, uterine cervix, elbow, groin, and thigh. Histologically, all cases except one were composed of monomorphic round to epithelioid cells showing an infiltrative multinodular growth pattern. The neoplastic cells were surrounded by a rich network of capillary vessels. Vessel invasion or subendothelial protrusion into the vascular space was commonly present. One tumor developed regional lymph node metastasis. The remaining case showed a predominantly spindle cell tumor. By immunohistochemistry, most tumors showed diffuse staining of CD56 (8/8) with variable expression of S100 protein (7/8). In three tumors harboring amplified genes, strong and diffuse nuclear staining of MDM2 (2/3) and CDK4 (3/3) were noted. Next-generation sequencing (NGS) studies revealed GLI1 fusions in 7 cases and GLI1 amplification in 2 cases, which were validated by fluorescence in situ hybridization (FISH) analysis in the majority of cases. One case did not show fusion gene by RNA-seq, but FISH revealed both amplification and break-apart of GLI1 gene. Follow-up information showed local recurrences in two patients. All other patients remained disease-free at the last follow-up. Our study further demonstrates that mesenchymal tumors with GLI1 alterations represent a distinctive clinicopathological entity. Although the tumor has a propensity for the tongue, it can also arise in somatic soft tissues as well as in visceral organs. Based on the characteristic morphological features and genomic profiles, we propose the term "GLI1-altered mesenchymal tumor" to describe this emerging entity.


Assuntos
Células Epitelioides , Neoplasias de Tecido Conjuntivo e de Tecidos Moles , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Células Epitelioides/patologia , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Masculino , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/patologia , Proteína GLI1 em Dedos de Zinco/genética
19.
Pathol Res Pract ; 229: 153700, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34929603

RESUMO

AIMS: Intracranial myxoid mesenchymal tumors (IMMTs) with fusions between EWSR1/FUS and CREB transcription factors have morphologic overlap with myxoid angiomatoid fibrous histiocytoma (mAFH) and myoepithelial tumor/carcinoma (MET/MEC). We aimed to study the clinicopathologic and genetic spectrum of extracranial IMMT-like tumors and their relationships with mAFH and MET/MEC. METHODS: Twelve extracranial tumors harboring EWSR1/FUS-CREB fusions across different histologic groups were characterized using RNA sequencing, FISH and/or RT-PCR. RESULTS: There were 4 IMMT-like neoplasms, 3 MET/MECs, and 5 mAFHs from the tibia (n=1), oral cavity (n=2), and soft tissues (n=9; 5 in the extremities), harboring EWSR1-ATF1 in 4 cases, FUS-CREM and EWSR1-CREM in 3 each, and EWSR1-CREB1 in 2. Multinodular growth, reticular/cording/trabecular arrangements, myxocollagenous matrix, and lymphocytic infiltrates variably prevailed among the 3 groups. mAFHs were characterized by cells with syncytial cytoplasm. IMMT-like neoplasms and MET/MECs shared cells with distinct boundaries, but only MET/MECs expressed GFAP and/or S100. MUC4 and ALK were expressed in some IMMT-like neoplasms (2/4; 2/4) and mAFH (2/5; 1/5). Pan-TRK reactivity was observed in two IMMT-like neoplasms with upregulated NTRK3 mRNA and one MEC. Local recurrences, typically ≥ 12 months postoperatively, developed in 2/3 IMMT-like neoplasms, 1/2 MET/MECs, and 0/4 mAFHs with follow-up. No definite associations were found between fusion types and histology, immunoprofile or outcome. CONCLUSIONS: We demonstrated the similarities and differences among 3 extracranial myxocollagenous tumor groups sharing EWSR1/FUS-CREB fusions. Oral IMMT-like neoplasms harboring FUS-CREM or EWSR1-ATF1 and FUS-CREM-positive.


Assuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/etiologia , Proteína de Ligação a CREB/fisiologia , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/diagnóstico , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/etiologia , Adulto , Idoso , Neoplasias Encefálicas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/patologia , Adulto Jovem
20.
Histopathology ; 80(1): 4-18, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34958503

RESUMO

Kinase alterations are increasingly recognised as oncogenic drivers in mesenchymal tumours. Infantile fibrosarcoma and the related renal tumour, congenital mesoblastic nephroma, were among the first solid tumours shown to harbour recurrent tyrosine kinase fusions, with the canonical ETV6::NTRK3 fusion identified more than 20 years ago. Although targeted testing has long been used in diagnosis, the advent of more robust sequencing techniques has driven the discovery of kinase alterations in an array of mesenchymal tumours. As our ability to identify these genetic alterations has improved, as has our recognition and understanding of the tumours that harbour these alterations. Specifically, this study will focus upon mesenchymal tumours harbouring NTRK or other kinase alterations, including tumours with an infantile fibrosarcoma-like appearance, spindle cell tumours resembling lipofibromatosis or peripheral nerve sheath tumours and those occurring in adults with a fibrosarcoma-like appearance. As publications describing the histology of these tumours increase so, too, do the variety kinase alterations reported, now including NTRK1/2/3, RET, MET, RAF1, BRAF, ALK, EGFR and ABL1 fusions or alterations. To date, these tumours appear locally aggressive and rarely metastatic, without a clear link between traditional features used in histological grading (e.g. mitotic activity, necrosis) and outcome. However, most of these tumours are amenable to new targeted therapies, making their recognition of both diagnostic and therapeutic import. The goal of this study is to review the clinicopathological features of tumours with NTRK and other tyrosine kinase alterations, discuss the most common differential diagnoses and provide recommendations for molecular confirmation with associated treatment implications.


Assuntos
Fibrossarcoma/genética , Rearranjo Gênico , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/genética , Nefroma Mesoblástico/genética , Receptor trkA/genética , Fibrossarcoma/patologia , Humanos , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/patologia , Nefroma Mesoblástico/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...