RESUMO
Dermatitis herpetiformis is a rare, chronic autoimmune disorder characterized by intense pruritic papules and vesicles, which can be associated with celiac disease and other autoimmune disorders. Its histologic characteristic is the accumulation of neutrophils within the papillary dermis with granular deposition of immunoglobulin A (IgA) observed under direct immunofluorescence. Herein, we report a 58-year-old woman who presented with a vesicular rash on the buttocks. The patient reported a recent history of genital herpes, Entamoeba histolytica colitis, recurrent hives, and eczema. A representative biopsy demonstrated features of spongiotic dermatitis and focal papillary dermal neutrophilic aggregates. Direct immunofluorescence revealed fibrillary IgA deposition in the papillary dermis, granular C3 deposition at the dermal-epidermal junction, and dermal papillae. The overall clinical, histologic, and DIF findings were consistent with those of dermatitis herpetiformis. The fibrillar IgA pattern is rare and easily overlooked by the unwary. Pathologists should be aware of this rare pattern, especially when the histologic findings are not classic.
Assuntos
Dermatite Herpetiforme/metabolismo , Dermatite Herpetiforme/patologia , Imunoglobulina A/metabolismo , Biópsia , Dermatite Herpetiforme/diagnóstico , Feminino , Técnica Direta de Fluorescência para Anticorpo , Humanos , Pessoa de Meia-Idade , Pele/patologiaRESUMO
Pityriasis rubra pilaris (PRP) is a rare, chronic, heterogeneous, papulosquamous inflammatory dermatosis of unknown etiology. Although erythematous scaly patches characterize the classic presentation of PRP, a broad range of clinical presentations has been reported. Histologically, PRP is characterized by psoriasiform acanthosis with alternating orthokeratosis and parakeratosis and rarely small acantholytic foci. In this article, we report a patient who presented with diffuse erythroderma and extensive acantholysis mimicking pemphigus vulgaris histologically.
Assuntos
Acantólise/patologia , Pênfigo/patologia , Pitiríase Rubra Pilar/patologia , Pele/patologia , Acantólise/tratamento farmacológico , Biópsia , Dermatite Esfoliativa/patologia , Diagnóstico Diferencial , Humanos , Imunossupressores/uso terapêutico , Pessoa de Meia-Idade , Pitiríase Rubra Pilar/tratamento farmacológico , Valor Preditivo dos Testes , Pele/efeitos dos fármacos , Esteroides/uso terapêuticoRESUMO
Merkel cell carcinoma (MCC) is an extremely aggressive skin cancer that must be distinguished from other basaloid cutaneous neoplasms that have different treatments and prognoses. This is sometimes challenging in small shave specimens, crushed samples, lymph nodes, and core needle biopsies. Insulinoma-associated protein 1 (INSM1) immunohistochemistry is a sensitive nuclear marker of neuroendocrine differentiation. INSM1 staining was performed on 56 MCC (47 primary tumors, 9 nodal metastases), 50 skin control cases that included basal cell carcinomas, basaloid squamous cell carcinomas, Bowen disease, sebaceous neoplasms, melanoma, and B-cell lymphomas, and 28 lymph node control cases that included metastatic neuroendocrine neoplasms, melanomas, squamous cell carcinomas, lymphomas, and adenocarcinomas. Percent of staining nuclei (0, <25%, 25% to 50%, 50% to 75%, >75%) and intensity (weak, moderate, strong) were recorded for each sample. All 56 MCC expressed INSM1. By comparison, synaptophysin, CK20, and chromogranin were expressed in 96%, 92%, and 32% of MCC, respectively. While the 3 conventional markers showed significant variability in staining intensity and distribution, INSM1 stained >75% tumor nuclei in 89% of MCC and 50% to 75% of tumor nuclei in 11%. Staining intensity was strong in 85% and moderate in 15%. None of the 50 cutaneous basaloid non-MCC neoplasms in the control group stained with INSM1, and among the lymph node controls 5 of 5 neuroendocrine neoplasms expressed INSM1, confirming that INSM1 staining cannot distinguish MCC from metastatic extracutaneous neuroendocrine carcinoma. INSM1 holds promise as a neuroendocrine marker that can distinguish MCC from its mimickers in the skin and improve detection of sentinel lymph node metastases.
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Biomarcadores Tumorais/análise , Carcinoma de Célula de Merkel/química , Imuno-Histoquímica , Linfonodos/química , Proteínas Repressoras/análise , Neoplasias Cutâneas/química , Idoso de 80 Anos ou mais , Carcinoma de Célula de Merkel/secundário , Diagnóstico Diferencial , Feminino , Humanos , Linfonodos/patologia , Metástase Linfática , Masculino , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Neoplasias Cutâneas/patologiaRESUMO
Adamantinoma-like Ewing sarcoma (AES) is a rare variant of Ewing sarcoma family of tumors (EFTs), primarily affecting bone and soft tissue. AES has mixed features of Ewing sarcoma (ES)/primitive neuroectodermal tumor (PNET) and adamantinoma with a complex immunoprofile and EWSR1 gene rearrangements. Herein, we report a 72-year-old male who presented with left parotid mass, right neck mass and thyroid nodules. Fine needle aspiration of the left parotid mass displayed nests of monotonous epithelioid cells with basaloid features in a background of small round blue cells and lymphocytes. AES can involve head and neck region and is characterized by groups of primitive small round blue cells admixed with groups of epithelioid cells with amphophilic cytoplasm and focal squamous differentiation. The proportion of these components can be variable, creating diagnostic challenges, particularly in unusual anatomic sites such as the parotid gland. However, when additional material is available, CD99 and/or FLI1 immunostains need to be included for diagnostic confirmation.
Assuntos
Adamantinoma/patologia , Citodiagnóstico/métodos , Glândula Parótida/patologia , Sarcoma de Ewing/patologia , Adamantinoma/cirurgia , Idoso , Biópsia por Agulha Fina , Diagnóstico Diferencial , Humanos , Masculino , Sarcoma de Ewing/cirurgiaRESUMO
Variants of papillary thyroid carcinoma (PTC) account for up to 25% of the cases, some of which are proven to be associated with aggressive clinical behavior such as tall cell and columnar cell variants. Hobnail variant of PTC (HVPTC) is recently described as a rare and aggressive variant of PTC. Herein, we are reporting a case of HVPTC in a patient who presented with hemoptysis and an intratracheal blood clot that was aspirated and submitted for cytopathological examination. Cytomorphology displayed neoplastic cells with profound micropapillary architecture, elongated nuclei, and prominent hobnail configuration. Nuclear features of PTC such as pseudoinclusions, nuclear overlapping, crowding, and grooves were readily identified. Subsequent total thyroidectomy revealed a 1.4 cm PTC with columnar and hobnail components. HVPTC is a rare locally aggressive subtype, which may present with metastasis from an occult thyroid primary. HVPTC needs to be included in the differential diagnosis of metastatic carcinoma with micropapillary architecture on fine needle aspiration, particularly in head and neck area. Diagn. Cytopathol. 2017;45:754-756. © 2017 Wiley Periodicals, Inc.
Assuntos
Carcinoma Papilar/patologia , Neoplasias da Glândula Tireoide/patologia , Idoso de 80 Anos ou mais , Humanos , Masculino , Câncer Papilífero da TireoideRESUMO
OBJECTIVE: Cytopathologic interpretation in Graves disease (GD) is considered challenging due to significant cellular atypia. STUDY DESIGN: We retrospectively identified 55 fine needle aspirations (FNAs) from 43 patients with GD that subsequently underwent thyroidectomy from 1995 to 2016. RESULTS: There were 5 patients with papillary thyroid carcinoma (PTC) and 4 with follicular adenoma (FA). Of the 5 patients with PTC, FNA was interpreted as PTC in 3, atypia of undetermined significance (AUS) in 1, and adenomatoid nodule (AN) in 1 (with a 0.5-cm incidental microcarcinoma). Of the 4 patients with FA, FNA was interpreted as follicular neoplasm (FN) in 2, AUS in 1, and AN in 1. Of the 46 nonneoplastic nodules, FNA was interpreted as nondiagnostic in 2, benign in 26, AUS in 15, FN in 1, and suspicious for PTC in 2. None was diagnosed as malignant. The sensitivity, specificity, positive predictive value, and negative predictive value of PTC diagnosis in FNA were 60, 100, 100, and 96.2%, respectively. CONCLUSION: FNA is a useful tool for identifying neoplastic nodules arising in GD. However, cytologic atypia often leads to indeterminate diagnoses (18/46, 39.1%). Awareness of clinical information regarding prior treatment for GD may be helpful to avoid overinterpretation.
Assuntos
Adenoma/diagnóstico , Biópsia por Agulha Fina , Carcinoma/diagnóstico , Doença de Graves/diagnóstico , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/diagnóstico , Adenoma/patologia , Adenoma/cirurgia , Adulto , Idoso , Carcinoma/patologia , Carcinoma/cirurgia , Carcinoma Papilar , Diagnóstico Diferencial , Erros de Diagnóstico/prevenção & controle , Feminino , Doença de Graves/patologia , Doença de Graves/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes , Estudos Retrospectivos , Câncer Papilífero da Tireoide , Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Nódulo da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/cirurgia , Tireoidectomia , Adulto JovemRESUMO
OBJECTIVES: Pancreatic serous cystadenomas (SCAs) are benign tumors. Technological advances in imaging have led to increased recognition of asymptomatic pancreatic cysts, consequently increasing the demand for cytomorphologic evaluations of cyst fluid. STUDY DESIGN: A retrospective search through the pathology archives over an 11-year period was performed to identify SCAs from pancreatectomy specimens with a presurgical pancreatic EUS-guided fine-needle aspiration (FNA). RESULTS: Fifty-one FNAs were identified. The average patient age was 59.9 years and 34 (67%) were female. Thirty-five (69%) of the SCAs were located in the body or tail of the pancreas. SCAs ranged in size from 1.3 to 8.0 cm (mean 4.9). On imaging, features suggestive of SCA were seen in 7 (14%) cases. The cytologic diagnoses were as follows: SCA in 5 (10%) cases, suspicious for mucin-producing neoplastic cyst in 4 (8%), pseudocyst in 4 (8%), and benign ductal and/or acinar epithelium, not otherwise specified in 24 (47%). Additionally, 14 (27%) cases were deemed nondiagnostic. CONCLUSIONS: A cytopathologic diagnosis of SCA on FNA is extremely difficult. The salient cytomorphologic features for identifying SCAs included scant cellularity, a mostly clear background, absence of extracellular mucin, hemosiderin-laden macrophages, and loose fragments of cuboidal cells with a notable absence of necrosis, atypia, and mitoses.
Assuntos
Cistadenoma Seroso/diagnóstico , Células Epiteliais/patologia , Macrófagos/patologia , Cisto Pancreático/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Cistadenoma Seroso/metabolismo , Cistadenoma Seroso/patologia , Cistadenoma Seroso/cirurgia , Diagnóstico Diferencial , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Células Epiteliais/metabolismo , Feminino , Hemossiderina/metabolismo , Humanos , Macrófagos/metabolismo , Masculino , Mucinas/metabolismo , Pâncreas/metabolismo , Pâncreas/patologia , Pâncreas/cirurgia , Pancreatectomia , Cisto Pancreático/metabolismo , Cisto Pancreático/patologia , Cisto Pancreático/cirurgia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Estudos RetrospectivosRESUMO
BACKGROUND: The sensitivity and specificity of positron emission tomography (PET) have been significantly improved for the identification of malignancies in recent years; however, it is still necessary to confirm PET findings in a lymph node (LN) by direct tissue sampling. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the most commonly used approach for diagnosing and staging mediastinal LNs, particularly in lung cancer patients with locally advanced disease. Despite this fact, evidence-based studies of EBUS-TBNA cytology and PET findings are still suboptimal. METHODS: The electronic database at the Johns Hopkins Medical Institutions and the pathology archives were searched to identify patients with mediastinal lymphadenopathy who had both EBUS-TBNA mediastinal LN sampling and a PET scan over a 14-month period. Patients suspected of having lung cancer and patients with a history of lung cancer were included in this study. Cytological diagnoses and follow-up surgical LN diagnoses were reviewed and correlated with PET scan findings. RESULTS: A total of 140 LNs from 79 patients, including 86 PET-positive LNs and 54 PET-negative LNs, were included. The most frequently sampled LNs were 4R and 7. The average size of PET-positive and PET-negative LNs was 1.2 and 1.6 cm, respectively. Among PET-positive LNs, 41.9% were malignant, 41.9% showed reactive changes or granulomatous inflammation, and 9.3% were nondiagnostic by EBUS-TBNA. However, among PET-negative LNs, 74.1% showed reactive changes or granulomatous inflammation, 7.4% were malignant, and 18.5% were nondiagnostic by EBUS-TBNA. CONCLUSIONS: The data demonstrate that EBUS-TBNA cytology improves the diagnostic accuracy of mediastinal LNs and clinical staging. Furthermore, EBUS-TBNA may identify additional malignant LNs (7.4%), and this highlights the risk for false-negative findings with PET scanning in isolation. Cancer Cytopathol 2017;125:717-25. © 2017 American Cancer Society.
Assuntos
Broncoscopia/métodos , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Idoso , Reações Falso-Negativas , Feminino , Humanos , Metástase Linfática , Masculino , Mediastino , Pessoa de Meia-Idade , Infecção por Mycobacterium avium-intracellulare/diagnóstico , Infecção por Mycobacterium avium-intracellulare/patologia , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons , Estudos RetrospectivosRESUMO
Monoclonal antibodies that block immune regulatory proteins such as programmed death-1 (PD-1) have demonstrated remarkable efficacy in controlling the growth of multiple tumor types. Unresectable or metastatic basal cell carcinoma, however, has largely gone untested. Because PD-Ligand-1 (PD-L1) expression in other tumor types has been associated with response to anti-PD-1, we investigated the expression of PD-L1 and its association with PD-1 expression in the basal cell carcinoma tumor microenvironment. Among 40 basal cell carcinoma specimens, 9/40 (22%) demonstrated PD-L1 expression on tumor cells, and 33/40 (82%) demonstrated PD-L1 expression on tumor-infiltrating lymphocytes and associated macrophages. PD-L1 was observed in close geographic association to PD-1+ tumor infiltrating lymphocytes. Additionally, we present, here, the first report of an objective anti-tumor response to pembrolizumab (anti-PD-1) in a patient with metastatic PD-L1 (+) basal cell carcinoma, whose disease had previously progressed through hedgehog pathway-directed therapy. The patient remains in a partial response 14 months after initiation of therapy. Taken together, our findings provide a rationale for testing anti-PD-1 therapy in patients with advanced basal cell carcinoma, either as initial treatment or after acquired resistance to hedgehog pathway inhibition.
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Anticorpos Monoclonais Humanizados/administração & dosagem , Antígeno B7-H1/imunologia , Carcinoma Basocelular/tratamento farmacológico , Receptor de Morte Celular Programada 1/imunologia , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Antígeno B7-H1/antagonistas & inibidores , Carcinoma Basocelular/genética , Carcinoma Basocelular/imunologia , Carcinoma Basocelular/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proteínas Hedgehog/antagonistas & inibidores , Proteínas Hedgehog/genética , Humanos , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologiaRESUMO
BACKGROUND: Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations and amplification are detected in 1% of primary lung adenocarcinomas (ADCs) and in 38% of primary lung squamous cell carcinomas. Alterations of PIK3CA in metastatic non-small cell lung carcinoma (NSCLC), however, are still not fully understood. This study investigated PIK3CA alterations in metastatic ADCs and correlated the findings with those for other commonly tested molecular abnormalities via fine-needle aspiration (FNA) and small-core biopsy materials. METHODS: This study identified 115 FNA cases of metastatic lung ADC with standard lung cancer panel analysis by targeted next-generation sequencing and fluorescence in situ hybridization at the Johns Hopkins Medical Institute over a 12-month period. The panel included mutational analysis of PIK3CA, AKT, BRAF, EGFR, ERBB2, KRAS, and NRAS genes and tests of rearrangements for ALK and ROS1 genes. RESULTS: A PIK3CA mutation was detected in 7 of 115 cases of metastatic ADC (6.1%). The majority of the mutations were located in exon 9 or exon 20; however, a mutation in exon 1 was seen in 1 case. Furthermore, p.V344G in exon 4 was detected in 2 cases. Among cases with PIK3CA mutations, 4 had coexisting EGFR mutations, whereas 2 had a coexisting BRAF or KRAS mutation. CONCLUSIONS: Several common mutations as well as a novel mutation in the PIK3CA gene were observed in metastatic NSCLC (particularly ADC). The unique role, however, of PIK3CA mutations in metastatic NSCLC and the clinical implications need to be further investigated. Cancer Cytopathol 2016;124:485-92. © 2016 American Cancer Society.
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Adenocarcinoma/genética , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células Escamosas/genética , Neoplasias Pulmonares/genética , Mutação/genética , Fosfatidilinositol 3-Quinases/genética , Adenocarcinoma/secundário , Idoso , Carcinoma Pulmonar de Células não Pequenas/secundário , Carcinoma de Células Escamosas/secundário , Classe I de Fosfatidilinositol 3-Quinases , Análise Mutacional de DNA , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Neoplasias Pulmonares/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: Fine-needle aspiration (FNA) biopsy of lung lesions is a highly accurate method for diagnosing and staging of lung cancers, particularly in patients with advanced cancer. Although, the majority of FNA cases of non-small cell lung carcinoma (NSCLC) can be subclassified by hematoxylin and eosin (H&E) sections, immunohistochemical (IHC) markers are usually necessary for difficult cases. Our previous study has shown that both P40 and P63 demonstrate differential sensitivity and specificity in the subclassification of squamous cell carcinoma (SqCC) using tumor tissue microarrays (TMA). In the present study, we further evaluated the utility of P40 and P63 and the potential pitfalls and limitations associated with the usefulness of these stains in FNA cases. METHODS: By a computer search of pathology archives, 144 FNA biopsies with diagnoses of lung cancers and P40/P63 stains were identified, including 50 adenocarcinomas (ADCs), 56 SqCCs, 8 small cell lung carcinomas (SCLCs), and 12 cases of poorly differentiated carcinoma (PD CA). Ten benign FNA lung lesions and 8 other malignant neoplasms were also included as controls. Nuclear staining patterns of P40 and P63 were scored semi-quantitatively as 0 (negative), 1 (<10%, weak and focal), or 2 (>10%, strong and diffuse). RESULTS: In lung SqCCs, P40 and P63 were positive in 77.3% and 89.5% cases, respectively. In ADCs, P40 was weakly and focally positive in 6.1% cases, and P63 was variably positive in 62.8% cases. In SCLCs, P40 and P63 were focally positive in 12.5% and 50% cases. In PD CAs, no P40 or P63 immunoreactivity was detected. In the group of other neoplasms (n=8) both P40 and P63 were positive in the case of metastatic non-seminomatous germ cell tumor (NSGCT) (n=1), and P63 was positive in the case of metastatic Merkel cell carcinoma (n=1). The sensitivity and specificity of P40 and P63 were 76.9%/93.3%, and 90.2%/50.7% in the lung SqCC. CONCLUSIONS: P63 has a better sensitivity, and P40 has a better specificity for SqCC. A positive staining pattern with both markers was also found in certain non-SqCC cases. Recognizing limitations of these markers are particularly important in FNA cases.
RESUMO
AIMS: NKX3.1 is an androgen-regulated tumour suppressor gene that is downregulated in prostate carcinoma. Immunohistochemistry for NKX3.1 is primarily specific for prostatic-derived tumours and tissue but is reported in a small number of breast carcinomas. NKX3.1 is also shown to inhibit estrogen receptor (ER) signalling in breast carcinoma models. Here, we investigate labelling of NKX3.1 in invasive ductal (IDC) and lobular (ILC) carcinomas of the breast with full characterisation of ER, progesterone receptor (PR), androgen receptor (AR) and Her2 status. METHODS: Tissue microarrays of 86 primary IDC and 37 ILC were labelled for NKX3.1. The IDC consisted of 20 luminal A, 7 luminal B, 14 Her2, and 45 triple negative carcinomas. The ILC consisted of 34 luminal A and 3 luminal B cases. NKX3.1 expression was scored as percentage nuclear labelling and labelling intensity. RESULTS: Nuclear NKX3.1 labelling was seen in 2 IDC (2%) and 10 ILCs (27%). labelling intensity was weak in all cases (1100% nuclear positivity). Positive NKX3.1 labelling was significantly associated with ILC (p<0.0001). NKX3.1 labelling was seen only in ER and AR-positive carcinomas, which showed a significant correlation (p=0.0003 and p=0.0079, respectively). Expression was not correlated with tumour stage, size, Her2 expression, presence of lymph node metastases or age. CONCLUSIONS: This is the first study to evaluate NKX3.1 expression in breast carcinomas with known ER, PR, AR and Her2 status. Further studies are needed to evaluate what potential role NKX3.1 plays in ER and AR signalling and hormonal treatment response in breast carcinomas.