RESUMEN
BACKGROUND: Crystal-storing histiocytosis (CSH) is a rare disorder which most commonly occurs in the setting of concurrent lymphoproliferative disease. Morphologically, it consists of aggregates of histiocytes containing eosinophilic crystalline material, which in most cases is composed of aggregated abnormal light chains. METHODS: Using histomorphology, immunohistochemistry and in situ hybridization, the authors characterize a rare case of orbital CSH associated with extranodal marginal zone (MALT) lymphoma and report for the first time the frozen section features of CSH. RESULTS: The frozen section featured plump histiocytes with ample weakly basophilic to grayish cytoplasm with a microvacuolated appearance and focal stippling. These features stand in contrast with the formalin-fixed, paraffin embedded histomorphological appearance of aggregates of plump histiocytes with densely eosinophilic crystalline cytoplasmic material. CONCLUSION: CSH is a challenging diagnosis to make on frozen section. The artifacts that preclude its recognition, as well as differential diagnoses of this entity in the head and neck are discussed.
Asunto(s)
Histiocitosis , Linfoma de Células B de la Zona Marginal , Humanos , Linfoma de Células B de la Zona Marginal/complicaciones , Linfoma de Células B de la Zona Marginal/patología , Histiocitosis/complicaciones , Histiocitosis/patología , Secciones por Congelación , InmunohistoquímicaRESUMEN
Phosphaturic mesenchymal tumors (PMT) are uncommon neoplasms that cause hypophosphatemia/osteomalacia mainly by secreting fibroblast growth factor 23. We previously identified FN1::FGFR1/FGF1 fusions in nearly half of the PMTs and frequent KL (Klotho or α-Klotho) overexpression in only those with no known fusion. Here, we studied a larger cohort of PMTs for KL expression and alterations. By FN1 break-apart fluorescence in situ hybridization (FISH) and reappraisal of previous RNA sequencing data, 6 tumors previously considered "fusion-negative" (defined by negative results of FISH for FN1::FGFR1 fusion and FGF1 break-apart and/or of RNA sequencing) were reclassified as fusion-positive PMTs, including 1 containing a novel FN1::ZACN fusion. The final cohort of fusion-negative PMTs included 33 tumors from 32 patients, which occurred in the bone (n = 18), soft tissue (n = 10), sinonasal tract (n = 4), and brain (n = 1). In combination with previous work, RNA sequencing, RNA in situ hybridization, and immunohistochemistry showed largely concordant results and demonstrated KL/α-Klotho overexpression in 17 of the 28 fusion-negative and none of the 10 fusion-positive PMTs studied. Prompted by a patient in this cohort harboring germline KL upstream translocation with systemic α-Klotho overexpression and multifocal PMTs, FISH was performed and revealed KL rearrangement in 16 of the 33 fusion-negative PMTs (one also with amplification), including 14 of the 17 cases with KL/α-Klotho overexpression and none of the 11 KL/α-Klotho-low fusion-negative and 11 fusion-positive cases studied. Whole genomic sequencing confirmed translocation and inversion in 2 FISH-positive cases involving the KL upstream region, warranting further investigation into the mechanism whereby these rearrangements may lead to KL upregulation. Methylated DNA immunoprecipitation and sequencing suggested no major role of promoter methylation in KL regulation in PMT. Interestingly, KL-high/-rearranged cases seemed to form a clinicopathologically homogeneous group, showing a predilection for skeletal/sinonasal locations and typically matrix-poor, cellular solitary fibrous tumor-like morphology. Importantly, FGFR1 signaling pathways were upregulated in fusion-negative PMTs regardless of the KL status compared with non-PMT mesenchymal tumors by gene set enrichment analysis, perhaps justifying FGFR1 inhibition in treating this subset of PMTs.
Asunto(s)
Mesenquimoma , Senos Paranasales , Neoplasias de los Tejidos Blandos , Humanos , Hibridación Fluorescente in Situ , Factor 1 de Crecimiento de Fibroblastos/genética , Neoplasias de los Tejidos Blandos/genética , Mesenquimoma/genética , Mesenquimoma/patología , Translocación Genética , Senos Paranasales/patologíaRESUMEN
BACKGROUND: Mucoepidermoid carcinoma is a malignant salivary gland tumor which, in most cases, is composed of variable proportions of mucous, epidermoid, and intermediate cells. METHODS: We report a case of parapharyngeal mucoepidermoid carcinoma with highly unusual ("monomorphic") light microscopic features as well as atypical immunohistochemical properties. Molecular analysis was performed using the TruSight RNA fusion panel. RESULTS: The tumor featured heretofore undescribed histopathological features: sheets and nests composed of monomorphic neoplastic (plump spindle to epithelioid) cells with no mucous, intermediate, glandular/columnar, or any other cell type identified. The neoplastic cells displayed variable clear cell change and only expressed cytokeratin 7. Despite this non-classical morphology, the presence of the classical CRTC1::MAML2 fusion was demonstrated. CONCLUSIONS: Mucoepidermoid carcinoma featuring a uniform ("monomorphic") population of neoplastic cells is a novel observation. A confident diagnosis of mucoepidermoid carcinoma can be made upon detection of the CRTC1/3::MAML2 fusion. Our case increases the spectrum of histopathological appearances that mucoepidermoid carcinoma may display.
Asunto(s)
Carcinoma Mucoepidermoide , Neoplasias de las Glándulas Salivales , Humanos , Proteínas de Unión al ADN/genética , Transactivadores , Carcinoma Mucoepidermoide/patología , Factores de Transcripción/genética , Neoplasias de las Glándulas Salivales/genética , Neoplasias de las Glándulas Salivales/patologíaRESUMEN
BACKGROUND: Oncocytic myoepithelial carcinoma ex pleomorphic adenoma neoplastic is a rare neoplastic event and may not display overt malignant radiological features. METHODS: Using routine histopathology and immunohistochemistry, we characterize a case of low-grade oncocytic carcinoma ex pleomorphic adenoma. RESULTS: The tumor arose in the left parotid gland in a 59 year old female. Computed tomography (CT) imaging demonstrated a well-defined, lobulated, enhancing lesion with relative central stellate hypoenhancement. Histologically, the tumor displayed a multi-nodular, non-destructive, invasive pattern, low mitotic activity (one mitotic figure per 10 high power fields) and a small remnant focus of pleomorphic adenoma. The neoplastic cells showed significant expression of cytokeratin 5/6, S-100 protein, smooth muscle actin and p63. CONCLUSION: Low-grade oncocytic carcinoma ex pleomorphic adenoma is a challenging histopathological diagnosis which can be established with use of immunohistochemistry, generous tumor sampling and recognition of the multi-nodular, non-destructive, pattern of invasion. In the absence of clear-cut tumor encroachment into external structures, its malignant nature may not be easily identified on pre-operative imaging.
Asunto(s)
Adenocarcinoma , Adenoma Pleomórfico , Neoplasias de la Parótida , Neoplasias de las Glándulas Salivales , Actinas/metabolismo , Adenocarcinoma/patología , Adenoma Pleomórfico/patología , Femenino , Humanos , Queratina-5/metabolismo , Persona de Mediana Edad , Neoplasias de la Parótida/diagnóstico , Proteínas S100 , Neoplasias de las Glándulas Salivales/diagnóstico , Neoplasias de las Glándulas Salivales/patología , Neoplasias de las Glándulas Salivales/cirugíaRESUMEN
This review summarizes the current state of knowledge on sclerosing polycystic adenoma, including epidemiological/clinical, histopathological/cytopathological, ultrastructural, immunohistochemical and etiopathogenetic/molecular genetic aspects. Differential diagnostic issues are briefly discussed.
Asunto(s)
Adenoma , Quistes , Adenoma/diagnóstico , Quistes/patología , Humanos , EsclerosisRESUMEN
We present a case of a 1.0 cm primary tumor of the left parotid gland that meets the histological criteria for the recently described entity sclerosing microcystic adenocarcinoma. The patient was a 73-year-old man with a concurrent tonsillar squamous cell carcinoma, and a history of nasopharyngeal carcinoma treated with radiotherapy 23 years prior. Fine needle aspiration cytology demonstrated low-grade biphasic basaloid neoplastic cells arranged in branching sheets and clusters with minimal nuclear pleomorphism. A biphasic appearance was apparent and some of the cell clusters were bordered by a layer of flattened cells with ovoid bland nuclei. On histology, the tumor comprised small bilayered infiltrative tubules, nests, cords, and microcysts. On immunohistochemistry, EMA, SOX-10, P63, and S-100 protein highlighted a dual cell population of luminal and abluminal cells. The cells were negative for CD117, and the Ki-67 proliferation index was low (<5%).
Asunto(s)
Adenocarcinoma/patología , Núcleo Celular/patología , Quistes/patología , Glándula Parótida/patología , Adenocarcinoma/diagnóstico , Anciano , Biopsia con Aguja Fina/métodos , Diagnóstico Diferencial , Humanos , MasculinoRESUMEN
We present a case (41 years old pregnant female) with epithelioid sarcoma arising in the left external auditory canal. On immunohistochemistry, the tumor cell diffusely expressed cytokeratins and showed patchy expression of ERG and CD34. The neoplastic cells demonstrated uniform loss of INI1-expression. Epithelioid sarcoma arising in the external auditory canal is rare. Awareness that ES may rarely arise at unusual sites is of critical importance in order to apply a broad enough panel in the immunohistochemical study, so a misdiagnosis of carcinoma can be avoided.
Asunto(s)
Conducto Auditivo Externo , Neoplasias del Oído/diagnóstico , Sarcoma/diagnóstico , Adulto , Biomarcadores de Tumor/análisis , Biopsia , Diagnóstico Diferencial , Neoplasias del Oído/patología , Femenino , Humanos , Imagen por Resonancia Magnética , Embarazo , Sarcoma/patología , Tomografía Computarizada por Rayos XRESUMEN
We describe a case of ectopic cervical thyroid tissue which was involved by fibrosing Hashimoto's thyroiditis and which mimicked metastatic papillary thyroid carcinoma both on fine needle aspiration cytology and biopsy. The patient underwent total thyroidectomy which revealed fibrosing Hashimoto's thyroiditis, but no carcinoma. The entire thyroidectomy specimen was submitted for histopathological assessment. Even in the resected thyroidectomy specimen, there were cytological changes that were strongly reminiscent of papillary thyroid carcinoma. However, interpreted in the correct clinico-pathological context, these cytological alterations were deemed to be reactive secondary to the fibro-inflammatory process.
Asunto(s)
Coristoma , Enfermedad de Hashimoto/diagnóstico , Enfermedad de Hashimoto/patología , Glándula Tiroides , Diagnóstico Diferencial , Femenino , Humanos , Persona de Mediana Edad , Cuello/patología , Cáncer Papilar Tiroideo/diagnóstico , Cáncer Papilar Tiroideo/patología , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/patologíaRESUMEN
We present two patients (29 and 67 years) with histomorphologic and immunohistochemical evidence of early high-grade transformation of adenoid cystic carcinoma in the nasal cavity and floor of mouth, respectively. The component of early high-grade transformation was characterized by 1) selective expansion of the luminal (CK7+, c-kit+, p63-) cell component with severe cytologic atypia and significantly increased Ki-67 proliferation index, and 2) retained albeit attenuated abluminal (CK7-, c-kit-, p63+) cells, surrounding nests of high-grade luminal cells.
Asunto(s)
Carcinoma Adenoide Quístico/patología , Desdiferenciación Celular/fisiología , Transformación Celular Neoplásica/patología , Índice Mitótico/métodos , Adulto , Anciano , Biomarcadores de Tumor/metabolismo , Carcinoma Adenoide Quístico/diagnóstico , Carcinoma Adenoide Quístico/radioterapia , Carcinoma Adenoide Quístico/cirugía , Femenino , Humanos , Inmunohistoquímica/métodos , Perdida de Seguimiento , Imagen por Resonancia Magnética/métodos , Boca/patología , Cavidad Nasal/patología , Terapia Neoadyuvante/métodos , Clasificación del Tumor/métodos , Resultado del Tratamiento , Trismo/diagnóstico , Trismo/etiologíaRESUMEN
We present 783 surgical resections of typical and atypical carcinoid tumors of the lung identified in the pathology files of 20 different pathology departments. All cases were critically reviewed for clinical and pathological features and further correlated with clinical outcomes. Long-term follow-up was obtained in all the patients and statistically analyzed to determine significance of the different parameters evaluated. Of the histopathological features analyzed, the presence of mitotic activity of 4 mitoses or more per 2 mm2, necrosis, lymphatic invasion, and lymph node metastasis were identified as statistically significant. Tumors measuring 3 cm or more were also identified as statistically significant and correlated with clinical outcomes. Based on our analysis, we consider that the separation of low- and intermediate-grade neuroendocrine neoplasms of the lung needs to be readjusted in terms of mitotic count as the risk of overgrading these neoplasms exceeds 10% under the current criteria. We also consider that tumor size is an important feature to be considered in the assessment of these neoplasms and together with the histological grade of the tumor offers important features that can be correlated with clinical outcomes.
Asunto(s)
Tumor Carcinoide/patología , Neoplasias Pulmonares/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Tumor Carcinoide/mortalidad , Tumor Carcinoide/cirugía , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Índice Mitótico , Clasificación del Tumor , Estadificación de Neoplasias , Neumonectomía , Factores de Tiempo , Resultado del Tratamiento , Carga Tumoral , Adulto JovenRESUMEN
Nasal metastases from colorectal cancer is rare. The presentation of nasal metastases is often very similar to primary nasal sinus adenocarcinoma. A high index of suspicion is required, especially in patients who have had a previous history of colorectal carcinoma. Histology is ultimately required for diagnosis. We describe 2 cases of nasal metastases from colorectal carcinoma, and discuss the presentation, diagnosis and management of the case. Such metastatic disease ultimately represents end-stage malignancy, and patients should be palliated.
Asunto(s)
Adenocarcinoma Mucinoso/genética , Carcinoma Secretor Análogo al Mamario/genética , Proteínas Proto-Oncogénicas c-ets/genética , Proteínas Proto-Oncogénicas c-ret/genética , Proteínas Represoras/genética , Neoplasias de las Glándulas Salivales/genética , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/patología , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Inmunohistoquímica , Carcinoma Secretor Análogo al Mamario/metabolismo , Carcinoma Secretor Análogo al Mamario/patología , Neoplasias de las Glándulas Salivales/metabolismo , Neoplasias de las Glándulas Salivales/patología , Translocación Genética , Proteína ETS de Variante de Translocación 6RESUMEN
A case of non-keratinizing, EBV-positive (chromogenic EBER-in situ hybridization), carcinoma with a hitherto undescribed nodular whorling architecture is presented. The patient is a 55 year old male with 2 months history of dermatomyositis who was diagnosed with T1N0M0 non-keratinizing nasopharyngeal carcinoma. The patient received radiotherapy with complete response. The tumor cells predominantly displayed spindle cell morphology, strongly expressed low-molecular weight cytokeratins (AE1-3), p63 and p40. There was no evidence of recurrence or disease progression on follow-up after 16 months which included post treatment biopsy, MRI and PET-CT scans.
Asunto(s)
Dermatomiositis/etiología , Infecciones por Virus de Epstein-Barr/complicaciones , Carcinoma Nasofaríngeo/patología , Neoplasias Nasofaríngeas/patología , Síndromes Paraneoplásicos/etiología , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo/complicaciones , Carcinoma Nasofaríngeo/diagnóstico , Neoplasias Nasofaríngeas/complicaciones , Neoplasias Nasofaríngeas/diagnósticoRESUMEN
We present the case of an uncommon example of a plexiform fibrohistiocytic tumor (PFHT) occurring in the anterior central neck region of a 40 year-old female with previous subtotal thyroidectomy. The tumor clinically mimics a complicated thyroglossal duct cyst. On fine needle aspiration cytology, the tumor was composed of sheets of bland spindle cells and nests of plump histiocytoid cells in vaguely whorled arrangements. Occasional multinucleated giant cells were also identified. The excised specimen showed an irregular, highly infiltrative subcutaneous tumor arranged in a nodular/plexiform pattern concentrated to the center of the tumor mass. In addition, the tumor contained numerous tongue-like extensions composed of variably cellular, fibroblastic/fibromatosis-like areas. These fibroblastic/fibromatosis-like extensions reached far from the epicenter of the tumor and were associated with scattered small plexiform nodules of histiocytic cells. These tongue-like extensions multifocally involved the surgical margins. The fibroblastic and histiocytoid cells showed diffuse smooth muscle actin (SMA) expression. The multinucleated giant cells and also the histiocytoid proliferation were positive for CD68. This case illustrates an uncommon both anatomical and demographic manifestation of PFHT and also characterize the fine needle aspiration cytologic features in this tumor, which previously have been reported in a few cases.
Asunto(s)
Neoplasias de Cabeza y Cuello/diagnóstico , Neoplasias de Cabeza y Cuello/patología , Neurofibroma Plexiforme/diagnóstico , Neurofibroma Plexiforme/patología , Adulto , Diagnóstico Diferencial , Femenino , Humanos , Quiste Tirogloso/diagnóstico , Quiste Tirogloso/patologíaRESUMEN
We present a case of a primary 2.5 cm pleomorphic lipoma of the right parotid gland with prominent myxoid change which on FNA displayed features that mimicked a carcinoma or sarcoma ex pleomorphic adenoma. The patient was a 79 year old man with no oncological history or tumor elsewhere. On immunohistochemistry the neoplastic cells strongly expressed CD34. There was no expression of retinoblastoma protein, smooth muscle actin, S100-protein or cytokeratins (AE1/3 and CAM5.2). The Ki-67 proliferation index was low (< 2%). Fluorescence in situ hybridization was negative for MDM2 gene amplification.
Asunto(s)
Lipoma/diagnóstico , Lipoma/patología , Neoplasias de la Parótida/diagnóstico , Neoplasias de la Parótida/patología , Adenoma Pleomórfico/diagnóstico , Anciano , Biomarcadores de Tumor/análisis , Biopsia con Aguja Fina , Carcinoma/diagnóstico , Diagnóstico Diferencial , Humanos , MasculinoRESUMEN
We present a 72 years old male with a left nasal cavity (mammary analogue) secretory carcinoma (SC) which exhibited classical morphological features on light microscopical examination, diffuse strong S100 and mammoglobin positivity on immunohistochemistry, and ETV6-NTRK3 gene fusion on next generation sequencing (NGS) analysis. Unusual features of this tumor are expression of p63 and DOG1 on immunohistochemistry and the atypical junction between Exon 4 of the ETV6 gene and Exon 14 of the NTRK3 gene.
Asunto(s)
Biomarcadores de Tumor/análisis , Carcinoma Secretor Análogo al Mamario/genética , Cavidad Nasal/patología , Neoplasias Nasales/genética , Proteínas de Fusión Oncogénica/genética , Anciano , Anoctamina-1/biosíntesis , Exones/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Carcinoma Secretor Análogo al Mamario/patología , Proteínas de la Membrana/biosíntesis , Proteínas de Neoplasias/biosíntesis , Neoplasias Nasales/patología , Análisis de Secuencia de ADNRESUMEN
A case of non-keratinizing, EBV-positive (EBER-in situ hybridization), carcinoma with adenomatous differentiation is presented. The patient is a 40 year old male with T2N2M0 disease who received standard combined chemo- and radiotherapy with complete resolution of all tumor. The tumor cells were strongly positive for low-molecular weight cytokeratins (AE1-3) and scattered cells expressed cytokeratin 20. No expression of cytokeratin 5/6, 7, p63, TTF-1, CDX2 or androgen receptor was detected. There was no evidence of recurrence or disease progression on follow-up after 19 months, which included post treatment MRI and PET-CT scans.
Asunto(s)
Carcinoma Nasofaríngeo/patología , Neoplasias Nasofaríngeas/patología , Adulto , Infecciones por Virus de Epstein-Barr/complicaciones , Humanos , Masculino , Carcinoma Nasofaríngeo/virología , Neoplasias Nasofaríngeas/virologíaRESUMEN
We present a 49 year old female with a diagnostically challenging myxoid solitary fibrous tumor arising in the soft tissue of the neck. The tumor was diffusely positive for CD34 and STAT6 on immunohistochemistry.