RESUMO
Ovarian mesonephric-like adenocarcinoma (MLA) is a rare tumor with potential origins in endometriosis and Müllerian-type epithelial tumors. The morphologic patterns of MLA overlap with those of endometrioid ovarian carcinoma (EnOC). We speculated that a subset of MLAs would be classified as EnOCs. In this study, we attempted to identify MLAs from malignant endometrioid tumors. Given that the study patients with MLAs had both endometrioid-like and mesonephric-like morphologies, we defined mesonephric-like differentiation (MLD) as an endometrioid tumor with focal or diffuse MLA morphology and immunophenotype. Twelve patients exhibited mesonephric-like morphologic patterns. Immunohistochemistry analysis for CD10, TTF-1, estrogen receptor (ER), GATA3, calretinin, and PAX8 expression was done using whole-section slides. Two patients without the MLA immunophenotype were excluded. Ten patients with EnOCs with MLD (8.3%) were identified from a cohort of 121 patients with malignant endometrioid tumors. All 10 patients were positive for TTF-1 and/or GATA3. Most patients were ER-negative. Morphologically, MLD was associated with papillary thyroid carcinoma-like nuclei, flattened cells, tubular, nested, reticular, or glomeruloid architecture, and infiltrative growth. All 10 patients had pre-existing endometriosis and/or adenofibromas. Among the EnOCs with MLD, 5 had coexisting components such as EnOC grade 1 [(G1), cases 4, 7, and 9], mucinous borderline tumor (case 1), and dedifferentiated carcinoma (case 10), with distinct borders between EnOC with MLD and the other components. Nine of the 10 MLA patients (90%) harbored KRAS hotspot mutations. In addition, 4 patients harboring other components shared common KRAS hotspot mutations. No significant prognostic differences were observed between patients with and without MLD. Based on our findings, we suggest that EnOC with MLD, especially in the early stages and without high-grade components, should be considered a subtype of EnOC. Overtreatment should be avoided in such patients, particularly in the early stages. In this study, as the characteristics between EnOC with MLD and MLA were not distinguishable, we considered both conditions to be on the same spectrum. EnOCs with MLD exhibit the MLA phenotype during disease progression and are prematurely classified as MLA. Nevertheless, more patients with EnOC who have MLD/MLA are required for a more robust comparison between conventional EnOC according to staging and grading.
Assuntos
Carcinoma Endometrioide , Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/classificação , Neoplasias Ovarianas/diagnóstico , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/classificação , Pessoa de Meia-Idade , Adulto , Idoso , Imuno-Histoquímica , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma/classificação , Fator de Transcrição GATA3/análise , Fator de Transcrição GATA3/metabolismo , Fator de Transcrição PAX8/análise , Fator de Transcrição PAX8/metabolismo , Diferenciação Celular , Endometriose/patologiaRESUMO
This study aimed to determine the clinicopathological predictive factors of peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS), and nodal T-follicular helper cell lymphoma, angioimmunoblastic-type (nTFH, AI-type). In this single-centered, retrospective study, medical records of 59 patients who were diagnosed with PTCL, NOS, or nTFH, AI-type from March 2007 to September 2022 were reviewed. The clinicopathological variables, including immunohistochemistry(IHC) subgroups, distinguishing TBX21 from the GATA3 subgroups were analyzed. Overall, 28 patients (75.7%) in the TBX21 group were PTCL, NOS. There were 9 (24.3%) patients in the GATA3 group. In univariable analyses, lymphoma subtype, age, and performance status were associated with progression-free survival (PFS), and overall survival (OS). In multivariable analyses, lymphoma subtype, and performance status were related to PFS and OS (P = 0.012, P < 0.001, P = 0.006, and P < 0.001, respectively). The GATA3 subgroup tended to have a worse prognosis in univariable analyses; however, it became more insignificant in multivariable when lymphoma subtype and performance status were adjusted (P = 0.065, P = 0.180, P = 0.972, and P = 0.265, respectively). The double-positive group showed variable prognoses of better PFS and worse OS. PD-1 and PD-L1 were associated with the EBV in situ hybridization (P = 0.027, and P = 0.005), and PD-1 was associated with CD30 expression (P = 0.043). This study demonstrated the potential of IHC classification to predict prognosis for PTCL, NOS, as well as nTFH AI-type, although further validation is necessary. Treatments targeting CD30, PD-1, and PD-L1 appear promising for lymphoma treatment.
Assuntos
Linfadenopatia Imunoblástica , Imunofenotipagem , Linfoma de Células T Periférico , Humanos , Linfoma de Células T Periférico/classificação , Linfoma de Células T Periférico/mortalidade , Linfoma de Células T Periférico/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Adulto , Linfadenopatia Imunoblástica/patologia , Linfadenopatia Imunoblástica/diagnóstico , Linfadenopatia Imunoblástica/mortalidade , Linfadenopatia Imunoblástica/classificação , Prognóstico , Idoso de 80 Anos ou mais , Proteínas com Domínio T/análise , Proteínas com Domínio T/metabolismo , Fator de Transcrição GATA3/análise , Células T Auxiliares Foliculares/imunologia , Taxa de SobrevidaRESUMO
Trichorhinophalangeal syndrome 1 (TRPS1) is a nuclear protein highly expressed in breast epithelial cells. TRPS1 immunohistochemistry (IHC) has been suggested as a breast cancer marker. To determine the diagnostic and prognostic utility of TRPS1 IHC, tissue microarrays containing 19,201 samples from 152 different tumor types and subtypes were analyzed. GATA3 IHC was performed in a previous study. TRPS1 staining was seen in 86 of 152 tumor categories with 36 containing at least one strongly positive case. TRPS1 staining predominated in various types of breast carcinomas (51%-100%), soft tissue tumors (up to 100%), salivary gland tumors (up to 46%), squamous cell carcinomas (up to 35%), and gynecological cancers (up to 40%). TRPS1 positivity occurred in 1.8% of 1083 urothelial neoplasms. In invasive breast carcinoma of no special type, low TRPS1 expression was linked to high grade ( P = 0.0547), high pT ( P < 0.0001), nodal metastasis ( P = 0.0571), loss of estrogen receptor and progesterone receptor expression ( P < 0.0001 each), and triple-negative status ( P < 0.0001) but was unrelated to patient survival ( P = 0.8016). In squamous cell carcinomas from 11 different sites, low TRPS1 expression was unrelated to tumor phenotype. Positivity for both TRPS1 and GATA3 occurred in 47.4% to 100% of breast cancers, up to 30% of salivary gland tumors, and 29 (0.3%) of 9835 tumors from 134 other cancer entities. TRPS1 IHC has high utility for the identification of cancers of breast (or salivary gland) origin, especially in combination with GATA3. The virtual absence of TRPS1 positivity in urothelial neoplasms is useful for the distinction of GATA3-positive urothelial carcinoma from breast cancer.
Assuntos
Biomarcadores Tumorais , Neoplasias da Mama , Proteínas de Ligação a DNA , Imuno-Histoquímica , Proteínas Repressoras , Análise Serial de Tecidos , Humanos , Biomarcadores Tumorais/análise , Feminino , Proteínas Repressoras/análise , Proteínas de Ligação a DNA/análise , Neoplasias da Mama/patologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/química , Neoplasias da Mama/diagnóstico , Fatores de Transcrição/análise , Fator de Transcrição GATA3/análise , Valor Preditivo dos Testes , Estimativa de Kaplan-Meier , PrognósticoRESUMO
Matrix Gla protein (MGP) and trichorhinophalangeal syndrome type 1 (TRPS1) have recently emerged as novel breast-specific immunohistochemical (IHC) markers, particularly for triple-negative breast cancer (TNBC) and metaplastic carcinoma. The present study aimed to validate and compare the expression of MGP, TRPS1 and GATA binding protein 3 (GATA3) in metastatic breast carcinoma (MBC), invasive breast carcinoma (IBC) with special features, including special types of invasive breast carcinoma (IBC-STs) and invasive breast carcinoma of no special type with unique features, and mammary and non-mammary salivary gland-type tumours (SGTs). Among all enrolled cases, MGP, TRPS1 and GATA3 had comparable high positivity for ER/PR-positive (p=0.148) and HER2-positive (p=0.310) breast carcinoma (BC), while GATA3 positivity was significantly lower in TNBC (p<0.001). Similarly, the positive rates of MGP and TRPS1 in MBCs (99.4%), were higher than in GATA3 (90.9%, p<0.001). Among the IBC-STs, 98.4% of invasive lobular carcinomas (ILCs) were positive for all three markers. Among neuroendocrine tumours (NTs), all cases were positive for TRPS1 and GATA3, while MGP positivity was relatively low (81.8%, p=0.313). In the neuroendocrine carcinoma (NC) subgroup, all cases were positive for GATA3 and MGP, while one case was negative for TRPS1. All carcinomas with apocrine differentiation (APOs) were positive for GATA3 and MGP, while only 60% of the cases demonstrated moderate staining for TRPS1. Among mammary SGTs, MGP demonstrated the highest positivity (100%), followed by TRPS1 (96.0%) and GATA3 (72.0%). Positive staining for these markers was also frequently observed in non-mammary SGTs. Our findings further validate the high sensitivity of MGP and TRPS1 in MBCs, IBC-STs, and breast SGTs. However, none of these markers are capable of distinguishing between mammary and non-mammary SGTs.
Assuntos
Biomarcadores Tumorais , Neoplasias da Mama , Fator de Transcrição GATA3 , Proteína de Matriz Gla , Neoplasias das Glândulas Salivares , Fatores de Transcrição , Feminino , Humanos , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/análise , Neoplasias da Mama/patologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas de Ligação ao Cálcio/análise , Proteínas de Ligação a DNA/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Fator de Transcrição GATA3/metabolismo , Fator de Transcrição GATA3/análise , Imuno-Histoquímica , Proteínas Repressoras/metabolismo , Neoplasias das Glândulas Salivares/patologia , Neoplasias das Glândulas Salivares/diagnóstico , Neoplasias das Glândulas Salivares/metabolismo , Sensibilidade e Especificidade , Fatores de Transcrição/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/diagnóstico , Neoplasias de Mama Triplo Negativas/metabolismoRESUMO
AIMS: Verruciform acanthotic vulvar intra-epithelial neoplasia (vaVIN) is an HPV-independent, p53 wild-type lesion with distinct morphology and documented risk of recurrence and cancer progression. vaVIN is rare, and prospective distinction from non-neoplastic hyperplastic lesions can be difficult. CK17, SOX2 and GATA3 immunohistochemistry has emerging value in the diagnosis of HPV-independent lesions, particularly differentiated VIN. We aimed to test the combined value of these markers in the diagnosis of vaVIN versus its non-neoplastic differentials in the vulva. METHODS AND RESULTS: CK17, SOX2 and GATA3 immunohistochemistry was evaluated on 16 vaVINs and 34 mimickers (verruciform xanthoma, lichen simplex chronicus, lichen sclerosus, psoriasis, pseudo-epitheliomatous hyperplasia). CK17 was scored as 3+ = full-thickness, 2+ = partial-thickness, 1+ = patchy, 0 = absent; SOX2 as 3+ = strong staining ≥ 10% cells, 2+ = moderate, 1 + =weak, 0 = staining in < 10% cells; and GATA3 as pattern 0 = loss in < 25% basal cells, 1 = loss in 25-75% basal cells, 2 = loss in > 75% basal cells. For analysis, results were recorded as positive (CK17 = 3+, SOX2 = 3+, GATA3 = patterns 1/2) or negative (CK17 = 2+/1+/0, SOX2 = 2+/1+/0, GATA3 = pattern 0). CK17, SOX2 and GATA3 positivity was documented in 81, 75 and 58% vaVINs, respectively, versus 32, 17 and 22% of non-neoplastic mimickers, respectively; ≥ 2 marker positivity conferred 83 sensitivity, 88 specificity and 86% accuracy in vaVIN diagnosis. Compared to vaVIN, SOX2 and GATA3 were differentially expressed in lichen sclerosus, lichen simplex chronicus and pseudo-epitheliomatous hyperplasia, whereas CK17 was differentially expressed in verruciform xanthoma and adjacent normal mucosa. CONCLUSIONS: CK17, SOX2 and GATA3 can be useful in the diagnosis of vaVIN and its distinction from hyperplastic non-neoplastic vulvar lesions. Although CK17 has higher sensitivity, SOX2 and GATA3 are more specific, and the combination of all markers shows optimal diagnostic accuracy.
Assuntos
Biomarcadores Tumorais , Fator de Transcrição GATA3 , Imuno-Histoquímica , Queratina-17 , Fatores de Transcrição SOXB1 , Neoplasias Vulvares , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/patologia , Carcinoma in Situ/metabolismo , Diagnóstico Diferencial , Fator de Transcrição GATA3/análise , Fator de Transcrição GATA3/imunologia , Fator de Transcrição GATA3/metabolismo , Imuno-Histoquímica/métodos , Queratina-17/análise , Queratina-17/imunologia , Queratina-17/metabolismo , Fatores de Transcrição SOXB1/análise , Fatores de Transcrição SOXB1/imunologia , Fatores de Transcrição SOXB1/metabolismo , Neoplasias Vulvares/patologia , Neoplasias Vulvares/diagnóstico , Neoplasias Vulvares/metabolismoRESUMO
CONTEXT.: Definitive diagnosis of metastatic triple-negative breast carcinoma (TNBC) is challenging on cytologic samples. Recent studies demonstrated that trichorhinophalangeal syndrome type 1 (TRPS1) is a highly sensitive and specific marker for diagnosing breast carcinomas, including TNBC, on surgical specimens. OBJECTIVE.: To evaluate TRPS1 expression in TNBCs on cytologic samples and a large series of nonbreast tumors on tissue microarray sections. DESIGN.: Immunohistochemical (IHC) analysis of TRPS1 and GATA-binding protein 3 (GATA3) was performed on 35 TNBC cases on surgical specimens, and 29 consecutive TNBC cases on cytologic specimens. IHC analysis of TRPS1 expression was also performed on 1079 nonbreast tumors on tissue microarray sections. RESULTS.: Of the surgical specimens, 35 of 35 TNBC cases (100%) were positive for TRPS1, all with diffuse positivity, whereas 27 of 35 (77%) were positive for GATA3, with diffuse positivity in 7 cases (26%). Of the cytologic samples, 27 of 29 TNBC cases (93%) were positive for TRPS1, with diffuse positivity in 20 cases (74%), whereas 12 of 29 (41%) were positive for GATA3, with diffuse positivity in 2 cases (17%). Of the nonbreast malignant tumors, TRPS1 expression was seen in 9.4% (3 of 32) of melanomas, 10.7% (3 of 28) of small cell carcinomas of the bladder, and 9.7% (4 of 41) of ovarian serous carcinomas. CONCLUSIONS.: Our data confirm that TRPS1 is a highly sensitive and specific marker for diagnosing TNBC cases on surgical specimens as reported in the literature. In addition, these data demonstrate that TRPS1 is a much more sensitive marker than GATA3 in detecting metastatic TNBC cases on cytologic samples. Therefore, inclusion of TRPS1 in the diagnostic IHC panel is recommended when a metastatic TNBC is suspected.
Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Neoplasias de Mama Triplo Negativas/diagnóstico , Neoplasias de Mama Triplo Negativas/patologia , Biomarcadores Tumorais/análise , Imuno-Histoquímica , Neoplasias da Mama/patologia , Bexiga Urinária/metabolismo , Fator de Transcrição GATA3/análise , Proteínas RepressorasRESUMO
Juxtaglomerular cell tumors and glomus tumors both arise from perivascular mesenchymal cells. Juxtaglomerular cells are specialized renin-secreting myoendocrine cells in the afferent arterioles adjacent to glomeruli, and juxtaglomerular tumors derived from these cells are therefore unique to the kidney. In contrast, glomus tumors have been described at numerous anatomic sites and may show significant morphologic and immunophenotypic overlap with juxtaglomerular tumors when occurring in the kidney. Although ultrastructural studies and immunohistochemistry for renin may distinguish these entities, these diagnostic modalities are often unavailable in routine clinical practice. Herein, we studied the clinicopathologic features of a large series of juxtaglomerular tumors (n = 15) and glomus tumors of the kidney (n = 9) to identify features helpful in their separation, including immunohistochemistry for smooth muscle actin (SMA), CD34, collagen IV, CD117, GATA3, synaptophysin, and renin. Markers such as SMA (juxtaglomerular tumors: 12/13, 92%; glomus tumors: 9/9, 100%), CD34 (juxtaglomerular tumors: 14/14, 100%; glomus tumors: 7/9, 78%), and collagen IV (juxtaglomerular tumors: 5/6, 83%; glomus tumors: 3/3, 100%) were not helpful in separating these entities. In contrast to prior reports, all juxtaglomerular tumors were CD117 negative (0/12, 0%), as were glomus tumors (0/5, 0%). Our results show that juxtaglomerular tumors have a younger age at presentation (median age: 27 years), female predilection, and frequently exhibit diffuse positivity for renin (10/10, 100%) and GATA3 (7/9, 78%), in contrast to glomus tumors (median age: 51 years; renin: 0/6, 0%; GATA3: 0/6, 0%). These findings may be helpful in distinguishing these tumors when they exhibit significant morphologic overlap.
Assuntos
Adenoma , Tumor Glômico , Neoplasias Renais , Actinas/análise , Adenoma/patologia , Adulto , Antígenos CD34/análise , Colágeno Tipo IV/análise , Feminino , Fator de Transcrição GATA3/análise , Tumor Glômico/química , Tumor Glômico/diagnóstico , Humanos , Sistema Justaglomerular/metabolismo , Sistema Justaglomerular/patologia , Sistema Justaglomerular/ultraestrutura , Rim/patologia , Neoplasias Renais/química , Pessoa de Meia-Idade , Renina/análise , Renina/metabolismo , Sinaptofisina/análiseRESUMO
GATA binding protein 3 (GATA3) belongs to a family of transcription factors comprising six members. These proteins identify G-A-T-A containing sequences in the target gene and bind to DNA target via two zinc-finger domains. The aim of this study was to evaluate the role of GATA3 in the diagnosis of tumors and its value as a prognostic marker. To perform this review, a comprehensive search was conducted through PubMed, Embase, Scopus, Cochrane and Google Scholar databases from 1985 to 2020. Articles were considered thoroughly by independent reviewers and data were extracted in predefined forms. Final synthesis was conducted by using appropriate data from included articles in each topic. Studies have shown that GATA3 has a critical role in the development of epithelial structures in both embryonic and adult tissues. The majority of studies regarding GATA3 expression in tumor evaluation focused on breast and urothelial neoplasms, whether primary or metastatic. Its sensitivity in these neoplasms has been reported to be high and made this marker more valuable than other available immunohistochemistry markers. However, GATA3 expression was not restricted to these tumors. Studies have shown that GATA3 immunostaining could be a useful tool in various tumors in kidney, salivary gland, endocrine system, hematopoietic system, and skin. GATA3 can also be used as a useful prognostic tool. Although GATA3 is a multi-specific immunohistochemical stain, it is a valuable marker in the panel for confirming many epithelial or mesenchymal neoplasms as both a diagnostic and prognostic tool.
Assuntos
Biomarcadores Tumorais/análise , Fator de Transcrição GATA3/análise , Neoplasias/diagnóstico , HumanosRESUMO
Urothelial carcinoma is subdivided into luminal (L), basal (B), and p53-wild-type (WT) molecular subtypes, with basal and p53-WT groups showing more aggressive course and poor treatment response, respectively. The literature on molecular subtypes of UC includes a mixture of different stages. We investigated the molecular profile and outcome of pure cohort of muscle invasive bladder carcinoma (MIBC) considering two distinct patterns of muscularis propria (MP) invasion. Forty-three cystectomies harboring stage pT2 were retrospectively identified in 18 years. MP invasion was subclassified into patterns 1 (tumor encasing intact detrusor muscle bundles) and 2 (tumor dissecting/replacing detrusor muscle). Using IHC, B/L phenotypes, p53, and Ki67 were assessed, and survival data was collected. Pattern 1 invasion was noted in 16 (37%) and pattern 2 in 27 (63%), with mean age of pattern 1 being 10 years younger. B/L phenotypes were successfully determined in 83.7%; 48.8% and 34.8% revealed L and B phenotypes, respectively (indeterminate phenotype in 16.4%). Pattern 1 was associated with L phenotype (GATA3 and HER-2 expressions: p = 0.02 & p = 0.04, respectively). Ki67 ≥ 5/10HPF was noted in pattern 2 and B phenotype (p = 0.03). B phenotype showed association with p53-WT (p = 0.007). In median follow-up of 60.7 months, 63.6% of pattern 1 cases were alive without disease compared to 32% of pattern 2 (not significant). A panel of CK20 and GATA3 for luminal and CK5/6 and CK14 for basal subtypes can provide reliable molecular classification in UC. Also, morphology of MIBC can predict the molecular phenotype and the behavior of the UC.
Assuntos
Biomarcadores Tumorais/análise , Carcinoma/química , Neoplasias da Bexiga Urinária/química , Urotélio/química , Idoso , Carcinoma/classificação , Carcinoma/patologia , Carcinoma/cirurgia , Cistectomia , Bases de Dados Factuais , Feminino , Fator de Transcrição GATA3/análise , Humanos , Imuno-Histoquímica , Queratina-14/análise , Queratina-20/análise , Queratina-5/análise , Queratinas Específicas do Cabelo/análise , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Fenótipo , Valor Preditivo dos Testes , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias da Bexiga Urinária/classificação , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia , Urotélio/patologia , Urotélio/cirurgiaRESUMO
Confirming the tumor origin is often a diagnostic challenge in pathology and carries significant therapeutic impacts. Cytokeratin 7, estrogen receptor, and GATA binding protein 3 (GATA3) are well-established diagnostic markers frequently used to support a tumor's breast origin. However, their specificities still have room to improve. Many nonbreast tumors express cytokeratin 7 and estrogen receptor, and urothelial tumors frequently express GATA3. There is a practical need for a new breast lineage marker that is sensitive and specific. Wnt family member proteins play critical roles in embryo development, tissue homeostasis and tumor development through ß-catenin dependent and independent pathways. The current study evaluated Wnt9b and GATA3 expression in 163 primary breast cancers, 63 metastatic breast cancers, and 525 nonbreast epithelial tumors. The positive rates of Wnt9b and GATA3 in primary breast cancer were both 98.7%. The positive rates in metastatic breast cancer were 87.3% for Wnt9b and 96.8% for GATA3. For nonbreast tumors, including 64 cases of urothelial carcinoma, Wnt9b was negative in all except salivary gland carcinomas. The study demonstrated that Wnt9b is a breast cancer marker with similar sensitivity as GATA3 but with greater specificity than GATA3 and may ultimately become a useful diagnostic tool in routine surgical pathology practice.
Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/química , Carcinoma/química , Fator de Transcrição GATA3/análise , Imuno-Histoquímica , Proteínas Wnt/análise , Neoplasias da Mama/patologia , Carcinoma/patologia , Feminino , Humanos , Masculino , Metástase Neoplásica , Valor Preditivo dos Testes , PrognósticoRESUMO
Acinic cell carcinoma of the breast is a rare subtype of triple-negative breast cancer that recapitulates the appearance of tumors seen in salivary glands. We present the case of a 42-year-old woman with an irregular, nontender mass above the left nipple during routine obstetric appointment at 24 weeks gestation. She was subsequently diagnosed with triple-negative invasive ductal carcinoma of the left breast, Nottingham grade 3, via core needle biopsy. She was treated with neoadjuvant therapy (doxorubucin and cyclophosphamide) antenatally and paclitaxel in the postpartum period followed by left mastectomy with sentinel node biopsy. The carcinoma in the mastectomy specimen showed a spectrum of morphologic patterns with immunohistochemistry revealing strong positivity for alpha-1-antichymotrypsin, epithelial membrane antigen (EMA), lysozyme, and S100. The histomorphology paired with the immunoprofile led us to the diagnosis of acinic cell carcinoma. We retrospectively performed immunostains in the core biopsy specimen, which demonstrated GATA-3 and DOG-1 positivity. Next-generation sequencing of the postneoadjuvant specimen using a 70-gene panel revealed 2 single-nucleotide variant (SNV) mutations: tumor protein 53 (TP53) (c.747G>T) SNV mutation and rearranged during transfection (RET) (c.2899G>A) SNV mutation.
Assuntos
Biomarcadores Tumorais/análise , Mama/patologia , Carcinoma de Células Acinares/diagnóstico , Complicações Neoplásicas na Gravidez/diagnóstico , Neoplasias de Mama Triplo Negativas/diagnóstico , Adulto , Anoctamina-1/análise , Anoctamina-1/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Mama/cirurgia , Carcinoma de Células Acinares/genética , Carcinoma de Células Acinares/patologia , Análise Mutacional de DNA , Feminino , Fator de Transcrição GATA3/análise , Fator de Transcrição GATA3/metabolismo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imuno-Histoquímica , Mastectomia , Proteínas de Neoplasias/análise , Proteínas de Neoplasias/metabolismo , Polimorfismo de Nucleotídeo Único , Gravidez , Complicações Neoplásicas na Gravidez/genética , Complicações Neoplásicas na Gravidez/patologia , Proteínas Proto-Oncogênicas c-ret/genética , Biópsia de Linfonodo Sentinela , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Proteína Supressora de Tumor p53/genéticaRESUMO
A 63-year-old woman presented with a clinically malignant mass. Core biopsy showed features resembling endometriosis. The glands were GATA3 and oestrogen receptor positive consistent with mammary origin and had no myoepithelial layer. The excision also showed a fibroepithelial component with stromal overgrowth, frequent mitoses and invasive margin consistent with a malignant phyllodes tumour. KMT2D and SETD2 mutations were present in both the conventional phyllodes tumour and endometriosis-like areas and are also described in endometriosis raising interesting questions about these lesions. This unusual pattern is a potential diagnostic pitfall, so it is helpful to be aware of it.
Assuntos
Neoplasias da Mama/patologia , Endometriose/patologia , Tumor Filoide/patologia , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Biópsia com Agulha de Grande Calibre , Neoplasias da Mama/química , Neoplasias da Mama/genética , Neoplasias da Mama/cirurgia , Análise Mutacional de DNA , Proteínas de Ligação a DNA/genética , Diagnóstico Diferencial , Endometriose/genética , Endometriose/metabolismo , Feminino , Fator de Transcrição GATA3/análise , Histona-Lisina N-Metiltransferase/genética , Humanos , Imuno-Histoquímica , Mastectomia , Pessoa de Meia-Idade , Mutação , Proteínas de Neoplasias/genética , Tumor Filoide/química , Tumor Filoide/genética , Tumor Filoide/cirurgia , Valor Preditivo dos Testes , Radioterapia Adjuvante , Receptores de Estrogênio/análise , Resultado do TratamentoRESUMO
Sarcomatoid malignant mesothelioma (SMM) tends to occur in the pleura and is morphologically similar to lung sarcomatoid carcinoma (LSC) and organizing pleuritis (OP). Because SMM often does not express mesothelial markers, it is very difficult to distinguish from LSC and OP. GATA-binding protein 3 (GATA3) is a specific immunohistochemical (IHC) marker of breast and urothelial carcinoma. We routinely find that GATA is expressed in MM; however, GATA3 expression in SMM and its reference value for distinguishing SMM from LSC and OP remain unclear. Here, we used IHC methods to detect the expression of GATA3 and classic mesothelial markers in 17 SMM, 12 LSC, and 7 OP cases. We detected the following expression rates in SMM versus LSC cases: GATA3 (70.6% vs. 16.7%, p = 0.008), calretinin (52.9% vs. 8.3%, p = 0.019), Wilms tumor (WT)-1 (64.7% vs. 0%, p = 0.000), D2-40 (47.1% vs. 16.7%, p = 0.126), CK5/6 (35.3% vs. 25.0%, p = 0.694), and pan-cytokeratin (CKpan) (88.2% vs. 100.0%, p = 0.498). The specificities of calretinin, WT-1, and GATA3 in distinguishing SMM from LSC were 91.7%, 100%, and 83.3%, respectively, and combinations of any two of these three markers exhibited 100% specificity for SMM. Notably, the sensitivity of calretinin+/WT1+ staining for SMM was only 23.5%, which increased to 64.7% after including GATA3. Furthermore, all OP cases showed partial or diffuse expression of CKpan, WT-1, and D2-40 but no GATA3 and calretinin expression. In conclusion, GATA3 is an IHC marker with excellent sensitivity and specificity for SMM, and the combined consideration of GATA3, calretinin, and WT-1 was best for distinguishing SMM from LSC. Moreover, CKpan, WT-1, and D2-40 had no value for distinguishing SMM from OP, and GATA3 and calretinin were the most specific markers for distinguishing these two lesions.
Assuntos
Biomarcadores Tumorais/análise , Carcinoma/química , Fator de Transcrição GATA3/análise , Imuno-Histoquímica , Neoplasias Pulmonares/química , Mesotelioma Maligno/química , Pleurisia/metabolismo , Sarcoma/química , Adolescente , Adulto , Idoso , Calbindina 2/análise , Carcinoma/patologia , Diagnóstico Diferencial , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Mesotelioma Maligno/patologia , Pessoa de Meia-Idade , Pleurisia/patologia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Sarcoma/patologia , Proteínas WT1/análise , Adulto JovemRESUMO
CONTEXT.: Endosalpingiosis is a benign Müllerian inclusion that can mimic metastatic low-grade mammary carcinoma, particularly when encountered in axillary lymph nodes excised for breast cancer staging. Immunohistochemistry can be useful in histologically ambiguous cases, and a targeted immunopanel should include a marker of gynecologic tract origin and a marker of mammary origin. GATA3 is a sensitive immunomarker for breast carcinoma, but the immunoreactivity of GATA3 in endosalpingiosis has not been systematically evaluated. OBJECTIVE.: To evaluate whether GATA3 immunohistochemistry could be used to differentiate endosalpingiosis from metastatic mammary carcinoma. DESIGN.: Whole slide sections of 15 cases of endosalpingiosis involving nonneoplastic tissues were subjected to GATA3 immunohistochemistry. Nuclear GATA3 labeling was scored as percentage and intensity labeling, with any labeling considered positive; GATA3 labeling was recorded in all cells present in the sections. RESULTS.: Half (47%, n = 7 of 15) of the endosalpingiosis cases involved lymph nodes (2 axillary, 5 pelvic) and half (53%, n = 8 of 15) involved pelvic organs or soft tissue (3 myometrial, 2 paratubal, 2 periadnexal soft tissue, and 1 pelvic sidewall). GATA3 immunohistochemistry was negative in all cases of endosalpingiosis, with intact, positive control labeling in lymphocytes. The benign fallopian tube epithelium present on the sections of paratubal endosalpingiosis displayed focal (<5%), weak labeling for GATA3, specifically within the ciliated and secretory cells. CONCLUSIONS.: These findings support the diagnostic utility of GATA3 immunohistochemistry and its use in a targeted immunopanel to resolve the differential diagnosis of metastatic low-grade mammary carcinoma (GATA3+) and nodal endosalpingiosis (GATA3-).
Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/química , Carcinoma/química , Fator de Transcrição GATA3/análise , Imuno-Histoquímica , Linfonodos/química , Doenças Linfáticas/metabolismo , Biópsia , Neoplasias da Mama/patologia , Carcinoma/secundário , Diagnóstico Diferencial , Feminino , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Linfonodos/cirurgia , Doenças Linfáticas/patologia , Doenças Linfáticas/cirurgia , Metástase Linfática , Valor Preditivo dos TestesRESUMO
Following lung cancer, breast cancer is the second most common metastatic tumor to the brain, of which triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2+ (HER2+) breast cancer are the most common subtypes. TNBC does not have standard immunoprofiles and can be difficult to distinguish from other metastases. A tissue microarray was created from 47 patients with breast cancer metastases to the brain and 12 paired breast primaries. Of 47 breast cancer metastases, 24 were HER2+, 14 were TNBC, and 9 were luminal. Forty-five were cytokeratin 7 (CK7) positive, 36 were GATA-binding protein 3 (GATA3) positive, 7 were Sry-related HMg-Box gene 10 (SOX-10) positive, 20 were mammaglobin positive, and 19 were gross cystic disease fluid protein 15 positive. At least one of the CK7, GATA3, or SOX-10 was positive in all TNBC metastases. A panel of CK7, GATA3, and SOX-10 is complementary in the diagnosis of breast cancer brain metastasis. SOX-10 appears to be a specific but not particularly sensitive marker in this context.
Assuntos
Biomarcadores Tumorais/análise , Neoplasias Encefálicas/diagnóstico , Fatores de Transcrição SOXE/análise , Neoplasias de Mama Triplo Negativas/patologia , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/secundário , Estudos de Casos e Controles , Estudos de Viabilidade , Feminino , Fator de Transcrição GATA3/análise , Fator de Transcrição GATA3/metabolismo , Humanos , Queratina-7/análise , Queratina-7/metabolismo , Pessoa de Meia-Idade , Fatores de Transcrição SOXE/metabolismo , Sensibilidade e Especificidade , Análise Serial de Tecidos , Adulto JovemRESUMO
Mycosis fungoides with large cell transformation (MFLCT) can be difficult to distinguish from primary cutaneous CD30+ T cell lymphoproliferative disorders (PC CD30+ LPD), especially primary cutaneous anaplastic large cell lymphoma (PC-ALCL). This diagnostic distinction is critical for appropriate patient management. GATA3 has been proposed to be useful in the discrimination between these two entities. We identified 25 cases of MFLCT and 24 cases of PC CD30+ LPDs (including lymphomatoid papulosis (n=14), PC-ALCL (n=6), and CD30+ LPD, not otherwise specified (n=4)) diagnosed at our institution from 2002 to 2019. Sections from archived specimens were stained to evaluate for GATA3 expression by immunohistochemistry and compared among cutaneous CD30+ T cell LPDs. The majority of the MFLCT cohort had strong, diffuse expression of GATA3 ranging from 0 to 100% of dermal T cells (mean 53.20%) with 15/25 cases (60%) showing GATA3 expression greater than 50%, while the PC CD30+ LPD group showed variable, moderate GATA3 labeling ranging from 0 to 60% of dermal T cells (mean 23.26%), with 5/6 cases (83%) showing GATA3 expression less than 40% (p =0.003). The calculated sensitivity and specificity were 56% and 74%, while positive and negative predictive values were 70% and 61%, respectively. Based on the percent staining of positive cells, using 50% as a cutoff value for expression, GATA3 might be a useful immunohistochemical marker to discriminate MFLCT from PC CD30+ LPDs, including PC-ALCL.
Assuntos
Biomarcadores Tumorais/análise , Fator de Transcrição GATA3/análise , Imuno-Histoquímica , Antígeno Ki-1/análise , Linfoma Anaplásico de Células Grandes/química , Papulose Linfomatoide/metabolismo , Micose Fungoide/química , Neoplasias Cutâneas/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Humanos , Linfoma Anaplásico de Células Grandes/imunologia , Linfoma Anaplásico de Células Grandes/patologia , Papulose Linfomatoide/imunologia , Papulose Linfomatoide/patologia , Masculino , Pessoa de Meia-Idade , Micose Fungoide/imunologia , Micose Fungoide/patologia , Valor Preditivo dos Testes , Estudos Retrospectivos , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Adulto JovemRESUMO
BACKGROUND: Bladder cancer is the ninth most common cancer worldwide, and the third most common cancer in Lebanon. Immunohistochemistry (IHC) has been used to stratify muscle-invasive bladder cancer (MIBC) into different subtypes. However, to our knowledge, there exists no study that investigates the use of this low-cost technique to predict prognosis in bladder cancer patients in our region. AIM: To examine the feasibility of low-cost triple-marker IHC assessment for MIBC subtyping in order to predict patients' survival and cisplatin sensitivity. METHODS AND RESULTS: We collected the specimens of deceased patients diagnosed with MIBC on pathology at our institution. For each case, tumor tissue blocks were retrieved and stained for hematoxylin and eosin in addition to three molecular markers by IHC: cytokeratin 5/6, cytokeratin 14 staining basal BC, and GATA3 staining luminal BC. A cut-off of ≥20% was set as positive. Kaplan-Meier curves were built, factored by BC subtype, to predict overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS). Hazard ratios in Cox regression were also created accounting for oncological factors and BC subtype. We categorized specimens as either luminal (GATA3 positive only) (n = 21; 56.7%) or as double-positive (GATA3 and basal cytokeratin 5/6 or cytokeratin 14 positive) (n = 16; 43.3%). The overall median survival was similar between the two categories (27.0 ± 4.82 months). Numbers favored luminal disease for PFS (Breslow P = .032). After adjusting for covariates, luminal molecular expression predicted PFS (0.28; [0.09-0.94]). Yet, the Cox model was not able to identify any predictors of OS or DSS. CONCLUSION: Specimens enriched with only a luminal molecular profile were more likely to exhibit cisplatin sensitivity. Despite the absence of guidelines recommending the utilization of molecular profiling in clinic practice, triple-marker IHC could serve as a potential low-cost prognostic indicator to identify patients at high risk of progression.
Assuntos
Biomarcadores Tumorais/análise , Músculos/patologia , Neoplasias da Bexiga Urinária/mortalidade , Bexiga Urinária/patologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Quimioterapia Adjuvante/métodos , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Cistectomia , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Feminino , Fator de Transcrição GATA3/análise , Fator de Transcrição GATA3/metabolismo , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Queratina-14/análise , Queratina-14/metabolismo , Queratina-5/análise , Queratina-5/metabolismo , Líbano/epidemiologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Projetos Piloto , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/terapiaRESUMO
Currently there is no highly specific and sensitive marker to identify breast cancer-the most common malignancy in women. Breast cancer can be categorized as estrogen receptor (ER)/progesterone receptor (PR)-positive luminal, human epidermal growth factor receptor 2 (HER2)-positive, or triple-negative breast cancer (TNBC) types based on the expression of ER, PR, and HER2. Although GATA3 is the most widely used tumor marker at present to determine the breast origin, which has been shown to be an excellent marker for ER-positive and low-grade breast cancer, but it does not work well for TNBC with sensitivity as low as <20% in metaplastic breast carcinoma. In the current study, through TCGA data mining we identified trichorhinophalangeal syndrome type 1 (TRPS1) as a specific gene for breast carcinoma across 31 solid tumor types. Moreover, high mRNA level of TRPS1 was found in all four subtypes of breast carcinoma including ER/PR-positive luminal A and B types, HER2-positive type, and basal-type/TNBC. We then analyzed TRPS1 expression in 479 cases of various types of breast cancer using immunochemistry staining, and found that TRPS1 and GATA3 had comparable positive expression in ER-positive (98% vs. 95%) and HER2-positive (87% vs. 88%) breast carcinomas. However, TRPS1 which was highly expressed in TNBC, was significantly higher than GATA3 expression in metaplastic (86% vs. 21%) and nonmetaplastic (86% vs. 51%) TNBC. In addition, TRPS1 expression was evaluated in 1234 cases of solid tumor from different organs. In contrast to the high expression of GATA3 in urothelial carcinoma, TRPS1 showed no or little expression in urothelial carcinomas or in other tumor types including lung adenocarcinoma, pancreatic adenocarcinoma, colon and gastric adenocarcinoma, renal cell carcinoma, melanoma, and ovarian carcinoma. These findings suggest that TRPS1 is a highly sensitive and specific marker for breast carcinoma and can be used as a great diagnostic tool, especially for TNBC.
Assuntos
Biomarcadores Tumorais/análise , Carcinoma/química , Imuno-Histoquímica , Proteínas Repressoras/análise , Neoplasias de Mama Triplo Negativas/química , Biomarcadores Tumorais/genética , Carcinoma/genética , Carcinoma/patologia , Bases de Dados Genéticas , Feminino , Fator de Transcrição GATA3/análise , Humanos , Valor Preditivo dos Testes , Proteínas Repressoras/genética , Reprodutibilidade dos Testes , Análise Serial de Tecidos , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
Immunohistochemistry is an essential component of diagnostic breast pathology. The emergence of novel assays and applications is accompanied by new interpretation criteria and potential pitfalls. Immunohistochemistry assists in supporting breast origin for primary or metastatic carcinomas and identifying non-mammary metastases to the breast; however, no single immunostain is perfectly sensitive nor specific. GATA3 and Sox10 are particularly useful immunostains to identify triple negative breast carcinoma, which are often negative for other markers of mammary differentiation. Sox10 labeling is a major potential diagnostic pitfall, as Sox10 and S-100 label both triple negative breast carcinoma and metastatic melanoma; a pan-cytokeratin immunostain should always be included for this differential diagnosis. Novel immunohistochemistry serves as surrogates for the molecular alterations unique to several of special-type breast carcinomas, including the use of MYB in adenoid cystic carcinoma, pan-TRK in secretory carcinoma, and mutant IDH2 in tall cell carcinoma with reversed polarity (TCCRP). In addition, PD-L1 immunohistochemistry is an emerging, albeit imperfect, biomarker for breast cancer immunotherapy, with different assay parameters and scoring criteria in breast carcinoma compared to other tumor types. The expanding repertoire of novel immunohistochemistry provides additional diagnostic tools and biomarkers that improve diagnostic breast pathology and patient care.
Assuntos
Neoplasias da Mama , Imuno-Histoquímica/métodos , Antígeno B7-H1 , Biomarcadores Tumorais/análise , Mama/patologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Carcinoma/diagnóstico , Carcinoma/patologia , Carcinoma Adenoide Cístico/diagnóstico , Carcinoma Adenoide Cístico/patologia , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/patologia , Diagnóstico Diferencial , Feminino , Fator de Transcrição GATA3/análise , Humanos , Fatores de Transcrição SOXE/análise , Neoplasias de Mama Triplo Negativas/diagnóstico , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
Distinguishing between poorly differentiated urothelial carcinoma and high-grade prostatic adenocarcinoma is a common challenge in genitourinary pathology, particularly when the tumor involves the bladder neck or prostatic urethra. Clinically, the distinction between these 2 tumors can also be difficult. Proper diagnosis in these patients is essential as they have differing prognoses and clinical management. GATA3 is thought to be a sensitive and relatively specific marker of urothelial carcinoma. However, there is scant data regarding GATA3 labeling of high-grade prostatic adenocarcinoma. The aim of this study is to describe rare cases with strong aberrant GATA3 staining in prostatic adenocarcinoma as a potential diagnostic pitfall. We identified 9 cases of prostatic adenocarcinoma with aberrant positive GATA3 staining from 2015 to 2020 as part of a large consultation service at our institution. All 9 cases were grade group 5, 8 had a Gleason score of 5+5=10 and 1 had a score of 4+5=9. Five of the cases were from the prostate, 3 from the urinary bladder, and 1 from the prostatic urethra. All cases were morphologically typical of high-grade prostatic adenocarcinoma, although were sent for consultation due to uncertainty in the diagnosis. GATA3 positivity was strong, diffuse in 4 cases; strong, patchy in 2 cases and strong, focal in 3 cases. All cases were positive for NKX3.1, 6 positive for p501s, and 6 positive for PSA, with 7/9 cases showing expression of at least 2 prostate-specific markers. The current study describes that rare cases of prostatic adenocarcinoma can show focal or diffuse strong staining for GATA3. In order to avoid this diagnostic pitfall, undifferentiated carcinomas involving the prostate, bladder neck, or trigone should be evaluated not only with GATA3 but also prostate-specific markers.