RESUMO
Neurotrophic receptor tyrosine kinase (NTRK)-rearranged spindle cell neoplasms are a recently described group of soft tissue tumors. They commonly present as a painless mass on the extremities of children and young adults. They are characterized microscopically by a heterogeneous spectrum of infiltrative spindle cell proliferations, which can morphologically mimic several other spindle cell neoplasms. Their identification is vital, as they may be amenable to treatment with tyrosine kinase-targeted therapy. This case report describes a rare NTRK3-rearranged spindle cell neoplasm in the groin of a 29-year-old female and provides further clinical and morphological features of this entity.
Assuntos
Virilha , Receptor trkC , Neoplasias de Tecidos Moles , Humanos , Feminino , Receptor trkC/genética , Adulto , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/diagnóstico , Virilha/patologia , Diagnóstico Diferencial , Rearranjo Gênico , Sarcoma/genética , Sarcoma/patologia , Sarcoma/diagnósticoRESUMO
Spindle cell lesions of the breast elicit a specific, relatively limited differential diagnosis, and accurate classification often requires careful morphologic evaluation and immunohistochemical workup. Low-grade fibromyxoid sarcoma (LGFMS) is a rare malignant fibroblastic tumor with deceptively bland spindle cell morphology. Involvement of the breast is exceedingly rare. We examined the clinicopathologic and molecular characteristics of three cases of breast/axillary LGFMS. In addition, we interrogated the immunohistochemical expression of MUC4, a commonly used marker of LGFMS, in other breast spindle cell lesions. LGFMS presented in women at 23, 33, and 59 years of age. Tumor size ranged from 0.9 to 4.7 cm. Microscopically, they were circumscribed nodular masses composed of bland spindle cells with fibromyxoid stroma. Immunohistochemically, tumors were diffusely positive for MUC4 and negative for keratin, CD34, S100 protein, and nuclear beta-catenin. Fluorescence in-situ hybridization demonstrated FUS (n = 2) or EWSR1 (n = 1) rearrangements. Next-generation sequencing identified FUS::CREB3L2 and EWSR1::CREB3L1 fusions. MUC4 immunohistochemistry performed on 162 additional breast lesions demonstrated only weak and limited expression in a subset of cases of fibromatosis (10/20, ≤30% staining), scar (5/9, ≤10%), metaplastic carcinoma (4/23, ≤5%), and phyllodes tumor (3/74, ≤10%). MUC4 was entirely negative in cases of pseudoangiomatous stromal hyperplasia (n = 9), myofibroblastoma (n = 6), periductal stromal tumor (n = 3), and cellular/juvenile fibroadenoma (n = 21). LGFMS can rarely occur in the breast and should be considered in the differential diagnosis of breast spindle cell lesions. Strong and diffuse MUC4 expression is highly specific in this histologic context. Detection of an FUS or EWSR1 rearrangement can confirm the diagnosis.
Assuntos
Fibroma , Fibrossarcoma , Neoplasias de Tecidos Moles , Humanos , Feminino , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Fibrossarcoma/genética , Imuno-Histoquímica , Diagnóstico Diferencial , Proteínas S100 , Fibroma/genética , Neoplasias de Tecidos Moles/patologiaRESUMO
Most salivary gland neoplasms are of epithelial origin. Sarcomas of the parotid gland, including leiomyosarcoma, are exceedingly rare mesenchymal tumours. A definitive diagnosis of leiomyosarcoma is challenging on cytomorphology alone. We herein describe a case of a 41-year-old woman who presented with parotid gland swelling. The patient was previously diagnosed with leiomyosarcoma of the parotid gland on histopathology. Fine needle aspiration cytology was done from this recurrent swelling. Cytomorphology combined with cell block immunocytochemistry was fruitful in confirming the tumour recurrence. Primary and recurrent/metastatic leiomyosarcoma of the parotid gland is a rarity and cannot be distinguished on cytology. Such a distinction is based on the known history of prior malignancy, which was forthcoming in the present case, or after an exhaustive work-up. Pertinent clinical history and radiology provide leads for the cytopathologist. They must be sought so that immunocytochemistry can be applied judiciously and a precise/nearly precise cytological diagnosis rendered, as it guides patient management. The diagnosis is challenging on cytology as the spindle cell lesions of the parotid gland range from reactive to benign to malignant tumours.
RESUMO
BACKGROUND: Inflammatory myofibroblastic tumors (IMTs) are rare intermediate-grade neoplasms that have a high recurrence rate after excision and exhibit low metastatic potential. These tumors contain proliferating neoplastic, fibroblastic and myofibroblastic cells, and are also characterized by chronic inflammatory infiltration by lymphocytes, plasma cells, eosinophils, and histiocytes. They belong to the group of inflammatory spindle cell lesions. Some reactive lesions, such as inflammatory pseudotumors, may appear to be IMTs, which makes their differential diagnosis extremely difficult. The aim of this article is to compile the recent information on IMTs to aid in their diagnosis and treatment. METHODS: We reviewed articles published between 2017 and 2021, which were selected from online medical databases. In addition, some earlier articles and latest scientific monographies were analyzed. RESULTS: The terminology used for inflammatory spindle cell lesions seems to be confusing. The terms "inflammatory myofibroblastic tumors" and "inflammatory pseudotumors" are interchangeably used by many scientists. However, a detailed analysis of the development of terminology suggests that the term "inflammatory myofibroblastic tumors" should be used to refer to a neoplastic lesion. CONCLUSIONS: IMTs are rare neoplasms, which have not been investigated in detail due to the difficulty in collecting a large number of cases. Thus, our knowledge about this disease remains unsatisfactory. Recently developed techniques such as next-generation sequencing and computer-aided histopathological diagnosis may be useful in understanding the etiopathology of IMTs, which will help in the selection of the most appropriate therapy for patients.
Assuntos
Granuloma de Células Plasmáticas , Diagnóstico Diferencial , Granuloma de Células Plasmáticas/diagnóstico , Granuloma de Células Plasmáticas/patologia , Granuloma de Células Plasmáticas/cirurgia , Humanos , Inflamação/patologia , Miofibroblastos/patologiaRESUMO
Spindle cell lesions of the breast comprise a heterogeneous group of lesions, ranging from reactive and benign processes to aggressive malignant tumours. Despite their rarity, they attract the attention of breast pathologists due to their overlapping morphological features and diagnostic challenges, particularly on core needle biopsy (CNB) specimens. Pathologists should recognise the wide range of differential diagnoses and be familiar with the diverse morphological appearances of these lesions to make an accurate diagnosis and to suggest proper management of the patients. Clinical history, immunohistochemistry, and molecular assays are helpful in making a correct diagnosis in morphologically challenging cases. In this review, we present our approach for the diagnosis of breast spindle cell lesions, highlighting the main features of each entity and the potential pitfalls, particularly on CNB. Breast spindle cell lesions are generally classified into two main categories: bland-appearing and malignant-appearing lesions. Each category includes a distinct list of differential diagnoses and a panel of immunohistochemical markers. In bland-appearing lesions, it is important to distinguish fibromatosis-like spindle cell metaplastic breast carcinoma from other benign entities and to distinguish fibromatosis from scar tissue. The malignant-appearing category includes spindle cell metaplastic carcinoma, stroma rich malignant phyllodes tumour, other primary and metastatic malignant spindle cell tumours of the breast, including angiosarcoma and melanoma, and benign mimics such as florid granulation tissue and nodular fasciitis.
Assuntos
Neoplasias da Mama , Carcinoma , Tumor Filoide , Mama/patologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Carcinoma/patologia , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Tumor Filoide/patologiaRESUMO
Desmoid fibromatosis (DF) involving the gastrointestinal tract is extremely rare. Its intramural location and occasional expansile growth pattern within the bowel wall may mimic a gastrointestinal stromal tumor (GIST). Due to the different disease behaviors and management, it is important to make a correct diagnosis before further treatment. We present an extremely rare case of a gastric DF that on imaging appeared as a discrete intramural mass mimicking a GIST and that was preoperatively correctly diagnosed as a DF based on its cytomorphologic, immunohistochemical, and molecular profiles. The patient is a 71-year-old female who presented with dysphagia and unintentional weight loss. A mass was identified at the gastric fundus. Endoscopic ultrasound-guided fine-needle aspirate (FNA) and biopsy (FNB) were performed. The FNA showed a few small aggregates of cytologically bland spindle-shaped cells with elongated nuclei. The FNB yielded small fragments of tissue composed of bland spindle cells demonstrating nuclear and cytoplasmic immunostain for ß-catenin and focal stain for smooth muscle actin (SMA) and desmin. CD117, DOG1, CD34, caldesmon, S100, cytokeratin AE1/AE3, signal transducer and activator of transcription 6 (STAT6), MUC4, progesterone receptor (PR), and anaplastic lymphoma kinase (ALK) were negative, and MIB-1 showed a very low proliferation activity index. Molecular studies performed by targeted next-generation sequencing showed activating mutations in CTNNB1. These results excluded a GIST and confirmed the diagnosis of a gastric DF. Although it is very rare, DF must be included in the differential diagnosis of discrete intramural gastric spindle cell lesions. A definitive diagnosis can be made preoperatively if enough lesional material is available for appropriate immunohistochemical and molecular studies.
RESUMO
Spindle cell lesions of the breast comprise a diverse set of tumors; harboring significant histological and immunohistochemical (IHC) overlap. Accurate diagnosis and classification of spindle cell lesions in the breast remains challenging, especially in core biopsies. In the current study, we evaluated a spectrum of spindle cell lesion of the breast with a panel of IHC antibodies in an effort to differentiate metaplastic spindle cell carcinoma from its benign and malignant mimickers. Our study included 92 patients who underwent breast core biopsies or breast resections at Northwell Health who were diagnosed with benign and malignant tumor/tumor-like spindle cell lesions. Tumors subtypes in this the study included: angiosarcoma, nodular fasciitis, fibromatosis, myofibroblastoma, phyllodes tumors (benign, borderline and malignant), primary sarcomas and metaplastic spindle cell carcinoma. Our biomarker panel included high molecular weight keratin (HMWK), CAM5.2, AE1/AE3, p63, CD34 and GATA3. GATA3 expression was significantly higher in metaplastic carcinomas (88.9 % vs 4.1 %, p < 0.001), when compared to other spindle cell lesions. The sensitivity and specificity for detecting metaplastic carcinomas reached 84.2 % and 97.3 %, respectively. Regarding cytokeratin panels, none of the three individual markers were as sensitive or specific for metaplastic breast carcinoma. GATA3 is the most specific and sensitive marker forfor the identification of metaplastic spindle cell carcinoma of the breast.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/diagnóstico , Carcinoma/patologia , Fator de Transcrição GATA3/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Metaplasia/patologia , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Leiomyomas are benign mesenchymal neoplasms mostly seen in the uterus and are one of the most common pelvic masses seen in women, but primary ovarian leiomyomas are rare among all the benign ovarian tumors, which account only for 0.5%-1%. The definitive diagnosis of such lesions is difficult prior to surgical excision, as there are no pathognomonic symptoms or characteristic imaging findings. Here, we report a case of primary ovarian leiomyoma with brief review of literature, highlighting the differential diagnosis of ovarian spindle cell lesions. The correct diagnosis of an ovarian leiomyoma requires identification of the nature of tumor as smooth muscle. An immunohistochemistry marker analysis is recommended for definitive diagnosis.
RESUMO
The diagnosis of spindle cell lesions of the breast parenchyma is challenging. Some of these lesions share the expression of CD34, posing differential diagnostic problems, especially in core biopsies. Recently, antibodies against the STAT6 C-terminal, are being used in paraffin-embedded tissues as a surrogate for identifying the NAB2-STA6 fusion gene which is considered a specific molecular marker for solitary fibrous tumor. Accordingly, we investigated the expression of STAT6 in a large series of uncommon spindle cell tumor-like and tumor lesions occurring primarily in the breast parenchyma. We collected 10 classic-type myofibroblastomas, 9 desmoid-type fibromatosis, 6 spindle cell metaplastic carcinoma, 5 benign fibroblastic spindle cell tumors, 3 solitary fibrous tumors, 7 pseudoangiomatous stromal hyperplasias, 2 reactive spindle cell nodules, 1 leiomyoma, 1 spindle cell lipoma, 1 case of inflammatory pseudotumor, 1 nodular fasciitis, 1 myxoma and 1 dermatofibrosarcoma protuberans. A diffuse and strong nuclear STAT6 expression was restricted only to solitary fibrous tumors, while the other lesions were negative or showed only weak cytoplasmic expression. The present study confirms that the demonstration of a diffuse and strong STAT6 nuclear staining is very helpful in distinguishing solitary fibrous tumor from other spindle cell mimics arising in the breast.
Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/diagnóstico , Fator de Transcrição STAT6/biossíntese , Tumores Fibrosos Solitários/diagnóstico , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Fator de Transcrição STAT6/análiseRESUMO
Spindle cell lesions of the breast comprise a wide-range of entities including reactive, benign and malignant proliferations. They can be pathologically challenging to differentiate as there is often immunohistochemical and morphologic similarities with characteristic spindle shaped cellular patterns. Radiological and pathological correlation is essential. Radiology detects, defines the size and extent, and assists in localizing the lesions. Pathology confirms the diagnosis and provides prognostic parameters. Familiarity with the clinicoradiological features of these diagnostically challenging lesions helps to establish an accurate pathological diagnosis and subsequent clinical decision making.
Assuntos
Neoplasias da Mama/diagnóstico por imagem , Diferenciação Celular/efeitos da radiação , Imagem Multimodal/métodos , Neoplasias da Mama/patologia , Diagnóstico Diferencial , Feminino , Humanos , PrognósticoRESUMO
Spindle cell carcinoma is a malignancy of epithelial origin often mimicking its mesenchymal counterpart thus posing a diagnostic challenge. It is a rare biphasic malignant tumour mostly encountered in the upper aerodigestive tract. The chief differential diagnoses of spindle cell carcinoma are true superficial sarcomas and they especially need to be differentiated from fibrosarcoma. This presentation reports a spindle cell carcinoma of the gingiva and highlights the difficulties encountered in the diagnosis. It also emphasizes the importance of accurate and thorough diagnosis of malignant spindle cell lesions to determine the appropriate therapeutic modality.
RESUMO
We herein report the clinical, radiological, and pathological findings of a rare case of a solitary fibrous tumor (SFT) occurring in the breast parenchyma of a 62-year-old female. The tumor was incidentally detected at a mammographic screening, and, ultrasonographically, presented as a single, well-circumscribed nodule. On needle core biopsy, the diagnosis of SFT was suggested based on a proliferation of CD34-positive spindly cells set in a fibrous stroma containing medium-sized blood vessels with hyalinization of their walls and branching configuration. The diagnosis was confirmed in the excised specimen, which exhibited a tumor with an immunohistochemical profile consistent with SFT, including diffuse expression of CD34, CD99 and bcl2. As STAT6 nuclear immunoexpression is the result of the inv12(q13q13)-derived NAB2-STAT6 fusion, which characterizes SFT, we analyzed immunohistochemically our case with a commercially available anti-STAT6 antibody. We showed that mammary SFT exhibits a diffuse nuclear STAT6 immunoreactivty, suggesting its potential diagnostic role. The present case emphasizes that the diagnosis of SFT can be confidentially rendered on needle core biopsy. Although SFT is suspected on characteristic morphologic features, immunohistochemistry, revealing immunoreactivity for CD34, bcl-2, CD99 and STAT6, is crucial in the differential diagnosis of potential benign and malignant mimics.
Assuntos
Neoplasias da Mama/diagnóstico , Fator de Transcrição STAT6/metabolismo , Tumores Fibrosos Solitários/diagnóstico , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Humanos , Imuno-Histoquímica , Mamografia , Pessoa de Meia-Idade , Tumores Fibrosos Solitários/diagnóstico por imagem , Tumores Fibrosos Solitários/metabolismo , Tumores Fibrosos Solitários/patologia , UltrassonografiaRESUMO
Although most breast spindle cell lesions (BSCLs) are rare, they constitute a wide spectrum of diseases, ranging from reactive processes to aggressive malignant tumours. Despite their varied histogenesis and behaviour, some lesions show an overlap of morphological features, making accurate diagnosis a challenging task, particularly in needle core biopsies. Clinical history and immunohistochemistry can help in making a correct diagnosis in morphologically challenging cases. To make an accurate diagnosis, it is important to maintain a wide differential diagnosis and be familiar with the diverse morphological appearances of these different entities. BSCLs can generally be classified into bland-looking and malignant-looking categories. In the former, the commonest diagnosis is scarring. However, it is important to distinguish low-grade spindle cell metaplastic breast carcinoma from other benign entities, as the management is clearly different. In the malignant category, it is important to differentiate metaplastic carcinoma from other malignant primary and metastatic malignant spindle cell tumours of the breast, such as malignant phyllodes tumour, angiosarcoma, and melanoma. This review focuses on the classification and histological and molecular diagnosis of various BSCLs, with an emphasis on the diagnostic approach, including in core biopsies.
Assuntos
Neoplasias da Mama/patologia , Mama/patologia , Tumor Filoide/patologia , Sarcoma/patologia , Diagnóstico Diferencial , Feminino , Fibroma/patologia , HumanosRESUMO
Although most salivary gland tumors can be diagnosed accurately on fine-needle aspiration, cytological evaluation of spindle cell lesions, including schwannomas, still poses a challenge. In salivary gland aspirates, the most important mimickers of schwannomas are the common pleomorphic adenomas/mixed tumors since these may yield abundant spindle-shaped myoepithelial cells and only scant epithelial cells. Therefore, in spindle cell-rich aspirates from the head and neck, diligent search for epithelial cells is recommended. Their presence traditionally favors pleomorphic adenoma and argues against a schwannoma. Herein, however, we report, for the first time, a schwannoma with epithelial elements (glandular schwannoma) in the submandibular gland, demonstrating that the presence of epithelial cells in a spindle cell-rich aspirate may not always exclude a schwannoma.
Assuntos
Adenoma Pleomorfo/diagnóstico , Células Epiteliais/patologia , Neurilemoma/diagnóstico , Neoplasias das Glândulas Salivares/diagnóstico , Adenoma Pleomorfo/patologia , Adulto , Biópsia por Agulha Fina , Diagnóstico Diferencial , Feminino , Histocitoquímica , Humanos , Neurilemoma/patologia , Neoplasias das Glândulas Salivares/patologia , Glândula Submandibular/patologiaRESUMO
AIMS: We examined gene rearrangement and the expression of anaplastic lymphoma kinase (ALK) in urinary bladder inflammatory myofibroblastic tumour (IMT) using fluorescence in-situ hybridization (FISH) and two immunohistochemical antibodies to ALK. We also investigated whether IMT represents an immunoglobulin (Ig)G4-related disease. METHODS AND RESULTS: The performance of the Dako FLEX ALK monoclonal antibody (CD246) and the Cell Signaling Technology ALK (D5F3) XP monoclonal antibody were compared. Overall, 11 of 16 tumours showed ALK expression by immunohistochemistry (69%). Ten demonstrated ALK expression with both stains and one was positive with D5F3 but not CD246 (91% correlation). The D5F3 antibody yielded a stronger staining intensity and a higher sensitivity. Nine tumours demonstrated ALK rearrangements (56%) by FISH. Three were ALK(+) by immunohistochemistry but negative for rearrangement by FISH, whereas one showed rearrangement by FISH but was negative by immunohistochemistry. In total, 12 tumours were positive for ALK abnormalities (75%). Using current criteria, no cases were classified as an IgG4-related disease. CONCLUSIONS: The ALK D5F3 immunohistochemical stain showed superior staining characteristics compared with ALK CD246. Discrepancies in the results between FISH and immunohistochemistry for ALK abnormalities may have causes that are multifactorial. By current criteria, IMT does not represent an IgG4-related disease.
Assuntos
Anticorpos Monoclonais/imunologia , Regulação Enzimológica da Expressão Gênica/fisiologia , Imunoglobulina G/fisiologia , Hibridização in Situ Fluorescente , Miofibroma/genética , Receptores Proteína Tirosina Quinases/genética , Neoplasias da Bexiga Urinária/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Quinase do Linfoma Anaplásico , Criança , Pré-Escolar , Feminino , Rearranjo Gênico/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Miofibroma/imunologia , Miofibroma/patologia , Receptores Proteína Tirosina Quinases/imunologia , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/patologia , Adulto JovemRESUMO
INTRODUCTION: Kaposi sarcoma (KS) is a rare disease that presents as 1 of 4 distinct clinicopathologic subtypes; however, it may present in populations outside those normally encountered. In such cases, it will be important to consider KS in the differential diagnosis, as it may mimic other neoplastic and non-neoplastic entities. MATERIALS AND METHODS: We describe 2 cases of KS, 1 in a patient not clinically fitting any of the 4 subtypes and the other in a patient with atypical presentation in human immunodeficiency virus (HIV)-associated disease. The first is an 81-year-old African American (AA) woman with a history of KS of the leg, who presented with groin lymphadenopathy and the second is a 42-year-old AA man with a known history of HIV infection, no skin lesions, and new axillary lymphadenopathy. RESULTS: Fine-needle aspiration of the groin and axillary lymph node, respectively, showed atypical spindle cells in a lymphoplasmacytic background. The spindle cells were positive for human herpesvirus-8 on the cell block and subsequent lymph node excision. In patients with HIV infection, in addition to reactive and lymphoproliferative processes, KS should be considered. In the former case, the demographic of an elderly AA woman without immunosuppression would not cause concern for systemic KS, but for a metastatic tumor or lymphoma. CONCLUSIONS: Cytology is a helpful tool in narrowing the differential diagnosis for spindle cell lesions. With a diagnosis of KS, clinicians would be able to query the clinical history for a possible etiology, such as HIV, and exclude the possibility of metastatic disease.
RESUMO
Solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm, most commonly arising from the pleura. It has also been recently described to occur in extrapleural sites. To our knowledge, only 16 cases of SFT have been reported in the urinary bladder to date. We report the clinicopathological features of a vesical SFT occurring in a 60-year-old man who presented a concomitant invasive high-grade urothelial cell carcinoma. No similar association has been found in the accessible literature. The morphologic and immunohistochemical clues leading to the correct diagnosis of SFT have been correlated with the data of the literature, and the differential diagnosis is briefly discussed.
Assuntos
Carcinoma de Células de Transição/patologia , Neoplasias Primárias Múltiplas/patologia , Tumores Fibrosos Solitários/patologia , Neoplasias da Bexiga Urinária/patologia , Biomarcadores Tumorais/análise , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade NeoplásicaRESUMO
One challenging feature of head and neck pathology is that a dizzying array of spindle cell lesions occur here ranging all the way from reactive to malignant and very aggressive. This makes accurate diagnosis critical. At mucosal sites, the most important of these is spindle cell carcinoma (SpCC). Most SpCC are overtly malignant, and the differential diagnosis then includes a number of different malignant spindle cell neoplasms. However, there are several benign or even non-neoplastic lesions that can sometimes be difficult to discern from SpCC. The pathologic and clinical features can resolve this differential diagnosis. This review will focus on the clinical and diagnostic features of SpCC and the select non-neoplastic or benign lesions which are occasionally hard to distinguish from it.