Analysis of GNAS gene variant in a Chinese pedigree affected with pseudohypoparathyroidism / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic etiology of a Chinese pedigree affected with pseudohypoparathyroidism.@*METHODS@#Peripheral blood samples of the proband and his parents were collected and subjected to trio-whole exome sequencing (trio-WES). Candidate variants were verified among the pedigree and 50 randomly selected healthy individuals through analysis of restriction fragment length polymorphism. Short tandem repeat (STR) linkage analysis was used to verify the parental origin of the pathogenic variants.@*RESULTS@#Trio-WES and Sanger sequencing showed that the proband and his mother had both harbored a c.121C>G (p.His41Asp) variant of the GNAS gene, which was not found in other family members and the 50 healthy controls. The variant was not found in international databases. Based on guidelines from the American College of Medical Genetics and Genomics, the variant was predicted to be likely pathogenic.@*CONCLUSION@#The novel c.121C>G variant of the GNAS gene probably underlay the disease in this pedigree. Above finding has enriched the spectrum of GNAS gene variants.

An analysis of GNAS and THRA gene mutations in children with congenital hypothyroidism / 中国当代儿科杂志

OBJECTIVE@#To preliminarily investigate the relationship between stimulatory G protein α subunit (GNAS) and thyroid hormone receptor α (THRA) gene mutations and clinical phenotypes in children with congenital hypothyroidism (CH).@*METHODS@#A total of 70 children with CH diagnosed by neonatal screening were enrolled. Their peripheral blood samples were collected to extract genomic DNA. GNAS and THRA genes were screened for mutations using next-generation sequencing. Bioinformatics software was used to analyze the pathogenicity of gene mutations.@*RESULTS@#Of the 70 children with CH, nine missense mutations (three known mutations and six novel mutations) in the GNAS gene were detected in three patients (4%), and one gene polymorphism, c.508A>G(p.I170V), in the THRA gene was detected in four patients. The analysis results of bioinformatics software and ACMG/AMP guidelines showed that the two GNAS gene mutations [c.301C>T(p.R101C) and c.334G>A(p.E112K)] were more likely to be pathogenic. Three children with GNAS gene mutations showed different degrees of hypothyroidism.@*CONCLUSIONS@#GNAS gene mutations are related to the development of CH, and children with CH have different clinical manifestations. THRA gene mutations may not be associated with CH.

Carcinoma neuroendocrino primario de vagina. Revisión de literatura a propósito de un caso / Primary neuroendocrine carcinoma of the vagina. Literature review on the subject of a case

RESUMEN El carcinoma primario de vagina representa 1 a 2% de los cánceres ginecológicos, siendo la diferenciación histológica neuroendocrina de células pequeñas extremadamente infrecuente, sólo se han reportado 28 casos en la literatura, describiéndose en orden de frecuencia en cérvix, endometrio, ovario, vagina y vulva. Se observa con más frecuencia en mujeres postmenopáusicas. Se presenta el caso de paciente femenino, de 39 años de edad, quien acude a la consulta por presentar secreción genital serohemática, fétida, de 1 mes de evolución, evidenciándose al examen físico lesión exofítica, friable, renitente, de aproximadamente 4 cm de diámetro, en tercio superior y cara posterolateral izquierda de vagina, por lo que se realiza biopsia excisional de dicha lesión, siendo el diagnóstico anatomopatológico carcinoma neuroendocrino de células pequeñas, grado histológico: 3. A propósito de este caso, se realiza una revisión del tema, haciendo hincapié en la importancia de la exploración ginecológica exhaustiva que incluya tomas de citologías y colposcopias periódicas, tomando en cuenta la vagina y así, realizar diagnóstico precoz en vista que el riesgo de carcinoma en dicha zona es infrecuente, mejorando el pronóstico y sobrevida de las pacientes.

ABSTRACT The primary carcinoma of the vagina represents 1 to 2 % of gynecologic cancers, being the histological differentiation neuroendocrine of small cells extremely infrequent, only 28 cases have been reported in the literature, describing in order of frequency: in the cervix, endometrium, ovary, vagina and vulva. It is most commonly seen in postmenopausal women. We present the case of a female patient, 39 years old, who comes to medical consult due to serohematic, fetid, genital discharge of 1 month of evolution, evidencing at physical examination an exophytic lesion, friable, renitent, with a diameter of approximately 4 cm, in the upper third and posterolateral left side of the vagina, for which an excisional biopsy of said lesion is performed, being the anatomopathological diagnosis neuroendocrine carcinoma of small cells, histological grade: 3. A bibliography reviewed was made, emphasizing the importance of exhaustive gynecological exploration with periodic cytology and colposcopy examinations, including the vagina for early diagnosis in view of carcinoma risk in this area is uncommon, improving the prognosis and survival of patients.

Circulating-free DNA Mutation Associated with Response of Targeted Therapy in Human Epidermal Growth Factor Receptor 2-positive Metastatic Breast Cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The addition of anti-human epidermal growth factor receptor 2 (HER2)-targeted drugs, such as trastuzumab, lapatinib, and trastuzumab emtansine (T-DM1), to chemotherapy significantly improved prognosis of HER2-positive breast cancer patients. However, it was confused that metastatic patients vary in the response of targeted drug. Therefore, methods of accurately predicting drug response were really needed. To overcome the spatial and temporal limitations of biopsies, we aimed to develop a more sensitive and less invasive method of detecting mutations associated with anti-HER2 therapeutic response through circulating-free DNA (cfDNA).</p><p><b>METHODS</b>From March 6, 2014 to December 10, 2014, 24 plasma samples from 20 patients with HER2-positive metastatic breast cancer who received systemic therapy were eligible. We used a panel for detection of hot-spot mutations from 50 oncogenes and tumor suppressor genes, and then used targeted next-generation sequencing (NGS) to identify somatic mutation of these samples in those 50 genes. Samples taken before their first trastuzumab administration and subsequently proven with clinical benefit were grouped into sensitive group. The others were collected after disease progression of the trastuzumab-based therapy and were grouped into the resistant group.</p><p><b>RESULTS</b>A total of 486 single-nucleotide variants from 46 genes were detected. Of these 46 genes, phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), proto-oncogene c-Kit (KIT), and tumor protein p53 (TP53) were the most common mutated genes. Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred m utations in the resistant group were associated with the resistance of targeted therapy. In addition, we detected a HER2 S855I mutation in two patients who had persistent benefits from anti-HER2 therapy.</p><p><b>CONCLUSION</b>Targeted NGS of cfDNA has potential clinical utility to detect biomarkers from HER2-targeted therapies.</p>

Extraskeletal myxoid chondrosarcoma: a report of 5 cases and review of literature / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features, immunophenotype and differential diagnosis of extraskeletal myxoid chondrosarcoma (EMC).</p><p><b>METHODS</b>The clinicopathologic features of 5 cases of EMC (during the period from 2008 to 2013) were retrospectively analyzed. Immunohistochemical study (EnVision method) was carried out using the archival material. The literature was reviewed.</p><p><b>RESULTS</b>There were altogether 3 female patients and 2 male patients. Their age ranged from 38 to 63 years (average = 51 years). The patients primarily presented with a tender soft tissue mass. All the tumors studied were solitary and the duration of disease onset varied from 3 months to 1 year. The sites of involvement included toe (number = 2), intracranial (number = 1), thigh (number = 1) and shoulder (number = 1). Gross examination showed white nodular masses with a gelatinous cut surface. The average tumor size measured 5.2 cm in greatest dimension. Histologically, a multinodular architecture with fibrous or loose fibrovascular septa separating lobules of tumor cells was identified. The lobules contained abundant myxoid stroma, with peripheral accentuation of tumor cellularity. Two cases were diagnosed as cellular variant of EMC, with invasive growth pattern and hemorrhage. The tumor cells in cellular EMC were arranged in solid nodules, with rare myxoid matrix in between. The nuclei were relatively uniform, round to oval and contained prominent nucleoli. The mitotic figure ranged from 5 to 10 per 10 high-power fields. Immunohistochemical study showed that all of the 5 cases were positive for vimentin, mitochondria and CD56. Two cases expressed synaptophysin and NSE. Focal positivity for these neuroendocrine markers was detected in the other 2 cases. Chromogranin and S-100 protein expression was demonstrated in 2 cases. The staining for epithelial membrane antigen was positive in case 2 and negative in the other 4 cases. CD117 showed diffuse positivity in case 1, the other 4 cases were not expressed.</p><p><b>CONCLUSIONS</b>EMC is a rare soft tissue sarcoma characterized by distinctive histopathologic features and often shows neuroendocrine differentiation. Although EMC is a slow-growing tumor, it carries a high local recurrence rate and even metastases, warranting long-term follow up.</p>

Association of T393C single nucleotide polymorphism of GNAS1 gene with non-valvular atrial fibrillation / 南方医科大学学报

<p><b>OBJECTIVE</b>To analyze the association between T393C single nucleotide polymorphism (SNP) of GNAS1 gene and non-valvular atrial fibrillation (AF) in Chinese Han patients.</p><p><b>METHODS</b>Ninety patients with non-valvular AF and 90 healthy subjects were examined for T393C SNP of GNAS1 gene using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The allele genotypes and the distribution of allele frequencies were analyzed and compared between the two groups. The relationship between allele frequency distribution characteristics and the heart rate variability (HRV) were also studied for analysis of the association between T393C SNP of GNAS1 gene and the autonomic nervous activation in non-valvular AF.</p><p><b>RESULTS</b>The two groups showed a significant difference in the frequencies of genotypes of T393C SNP of GNAS1 gene and allele frequencies (P<0.01). CC genotype and T393C allele frequency were significantly increased in the case group. pNN50, LF, or LF/HF showed no significant difference between different genotypes (P<0.05).</p><p><b>CONCLUTIONS</b>The T393C SNP of GNAS1 gene is closely associated with non-valvular AF in Chinese Han patients.</p>

Clinical features, mutation of the GNAS1 and pathogenesis of progressive osseous heteroplasia / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the clinical features, mutation of the GNAS1 and pathogenesis of progressive osseous heteroplasia (POH).</p><p><b>METHOD</b>The typical clinical, pathological and radiographic features of a boy with POH were collected and summarized following family survey. The GNAS1 gene sequence of all family members were amplified by polymerase chain reaction (PCR) and the products were sequenced directly to identify the mutations. A literature review and long-term follow up were also conducted.</p><p><b>RESULT</b>The patient was an 11-year-old boy who had the onset in infancy, which indicates a chronic progressive cause of disease. The clinical features include the unsmooth local skin of the right shank where spread many rigid rice-like or irregular slabby uplifts, slabby bone-like sclerosis on the left lower mandible, left masticatory muscles, in lateral subcutaneous site of left hip joint and deep tissue, accompanied by gradually progressive difficulty in opening mouth. Histopathology showed that there were loosened hyperplasia of fibroblast and interstitial edema with punctiformed ossification. Radiographs showed flocculence hyperdense image in the subcutaneous tissues and muscles around left lower mandible, and the left masticatory muscles were obviously involved. The 3-dimensional computed tomography showed dislocations of the left temporomandibular joint. Sheeted hyperdense image with inequable density could be noted in lateral muscles of the left hip. And lamellar hyperdense image parallel to the long axis of the bone could be seen in the subcutaneous dorsum of the left foot and achilles tendon. Macro-thumb and of brachydactylia of the hands and feet were not present. The level of calcium, phosphorus and alkaline phosphatase in the blood were normal. Brother of same father but different mothers was free of the disease and no patient of the same disease was found in maternal line and paternal lines. A mutated allele in exon 7 and a polymorphism in exon 5 were found in GNAS1 gene in both of the patient and his father.</p><p><b>CONCLUSION</b>There is possibility/likelihood/probability that Chinese children could develop POH. Translocated dermal ossification began in infancy and shows a progressive cause in childhood. The disease is characterized by the heterotopic ossification of the skin, deep tissue, muscles and facial surface tissues. The location of the mutation in this study was different from that reported in abroad studies although exist in the same exons.</p>

Neuroendocrine carcinoma of breast: a study of tumor morphology and subtyping / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinical features and histopathology of the neuroendocrine carcinoma (NEC) of the breast.</p><p><b>METHODS</b>Twenty-two cases of NEC of the breast were analysed by morphology and immunohistochemistry using synaptophysin, chromogranin A, NSE, CD56, estrogen receptor (ER), progesterone receptor (PR), HER2, EGFR, CK5/6, CK14, p63, E-cadherin, p120, p53 and Ki-67 staining. HER2 gene amplification was detected by fluorescence in situ hybridization (FISH) for cases with HER2 protein expression 2+. The diagnosis of breast NEC relies on the expression of neuroendocrine markers expression in more than 50% of tumor cells, and no evidence of neuroendocrine carcinoma in any other parts of the body at the same time.</p><p><b>RESULTS</b>The patients aged from 31 to 96 years (mean 65.2 years), and all were female but one. Amongst the 22 patients studied, the NECs were in the left breast in 15 cases (68.2%) and in the right breast in seven cases (31.8%); the tumor size was 0.5 to 5.5 cm (mean 2.7 cm). Lymph node metastasis was found in six cases. Basing on the morphologic features, these 22 cases were categorized into six subtypes including nine cases of solid cohesive, six of mucinous, three of solid papillary, two of small cell, one of large cell and one of alveolar variants. Immunohistochemically, the expression rate of markers was 100% (22/22) for synaptophysin, 12/13 for NSE, 54.5% (12/22) for chromogranin A, and 5/16 for CD56. Also, 90.5% (19 of 21) of cases expressed ER, 81.0% (17 of 21) of cases expressed PR, and none expressed EGFR, CK5/6, CK14 and p63. HER2 protein over-expression (3+) and gene amplification was not detected in any case. All cases (19/19) were positive for membrane staining for E-cadherin and p120. p53 expression was seen in 6 of 17 cases. Ki-67 labeling index was less than 3% in 9.5% (2/21) of the cases, 3% to 20% in 66.7% (14/21) of the cases and more than 20% in 23.8% (5/21) of the cases. Both cases of HER2 (2+) did not show gene amplification by FISH. On the basis of immunophenotypes, most of the breast NECs were of the luminal molecular subtype, but not HER2-overexpression or basal-like subtypes.</p><p><b>CONCLUSIONS</b>NEC of breast more likely occurs in elderly patients and in the left breast than the right breast. The most common morphology is the solid cohesive subtype, followed by the mucinous variant.</p>

Synchronous Large-Cell Neuroendocrine Carcinoma and Adenocarcinoma of the Colon

Large-cell neuroendocrine carcinoma of the colon is a rare entity with a prognosis that is usually poor due to the high likelihood of early metastasis. A 61-year-old man had surgery for colon cancer of the transverse colon and cecum. Microscopic examination of the tumor showed that the location was the proximal transverse colon, with small nests containing rosettes and palisading patterns of large tumor cells with faintly granular cytoplasm. The immunohistochemistry was positive for synaptophysin and chromogranins. The tumors were diagnosed as a large-cell neuroendocrine carcinoma of the colon. In addition, the tumor of the cecum showed microscopic findings consistent with a well-differentiated adenocarcinoma. The immunohistochemical panel showed that the tumor was negative for neuroendocrine markers. There were no clinical findings suggestive of hormone hypersecretion. Cancer metastasis was found in the peritoneum section of the small bowel. Postoperative chemotherapy was applied. The patient was alive with good performance after, and there was no sign of tumor progression. This is the first case of a synchronous large-cell neuroendocrine carcinoma and adenocarcinoma of the colon. The patient was treated successfully with debulking surgery and systemic chemotherapy.

Primary neuroendocrine carcinoma of the breast.

Primary neuroendocrine carcinoma of the breast is rare-only about 30 cases have been reported in literature. Immunohistochemical examination showing expression of chromogranin and/or synaptophysin confirms evidence of neuroendocrine differentiation. Usually foci of neuroendocrine differentiation can be seen in breast carcinoma and are reported to be present in about 2-5% of breast cancer cases. Here, we report a case of breast carcinoma in which most of the areas studied on the tissue section showed neuroendocrine differentiation.

Abnormal expression of c-myc, p53, p16 protein and GNAS1 gene mutation in fibrous dysplasia / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the significance of c-myc, p53 and p16 protein expression in fibrous dysplasia, to detect the GNAS1 gene mutation in fibrous dysplasia, and to explore the property of fibrous dysplasia.</p><p><b>METHODS</b>The expression of c-myc, p53 and p16 protein was evaluated by immunohistochemistry SP method in 35 cases of fibrous dysplasia including 1 FD with malignancy, 1 Mazabraud syndrome and 20 control cases (10 cases of bony callus, 10 cases of osteosarcoma). Genomic DNA extraction, PCR amplification and gene sequencing were used to detect GNAS1 gene mutation in 35 cases of fibrous dysplasia.</p><p><b>RESULTS</b>C-myc protein immunoreactivity was detected in 91 percentage of FD (P = 0.001). Compared with the negative control group, the difference was significant. P16 positive was detected in 34 FD cases (P = 0.001). The difference was significant as compared with the positive control group. Positive p53 protein expression was detected in the only 1 case of fibrous dysplasia with malignant transformation. PCR amplification was successful in 12 of 35 FD cases. Two of the 12 FD cases were detected to have GNAS1 gene mutation, in which 1 case was FD of Mazabraud syndrome, 1 case was a monostotic lesion.</p><p><b>CONCLUSIONS</b>C-myc could be another protooncogene in addition to c-fos in the fibrous dysplasia disease. P53 protein overexpression could be useful in the diagnosis of FD malignancy and in the prediction of the prognosis of FD. The abnormal expression of the gene p16 might play an important role in the formation of FD. The GNAS1 mutation exist in FD. All of the results indicate that FD could be a neoplasia disease, caused by multiple factors leading to a dysfunction of bone development.</p>

A Case of Easily Overlooked Small Duodenal Carcinoid Tumor / 대한소화기학회지

No abstract available.

Extrapulmonary Small Cell Carcinoma of the Liver: Clinicopathological and Immunohistochemical Findings

Patients with primary small cell carcinoma of the liver have rarely been described in medical literature. Knowledge of clinical, pathological and immunohistochemical properties remains limited. We described an 82-year-old female patient with primary small cell carcinoma of the liver. Histologically, the tumor showed typical morphology of a pulmonary small cell carcinoma. Immunohistochemically, the tumor revealed neuroendocrine differentiation; positive reaction for chromogranin, synaptophysin, CD56, and neuron specific enolase. The tumor was also positive for TTF-1 and c-kit but completely negative for hepatocyte, carcinoembryonic antigen, cytokeratin 7; 19; and 20. Herein, we discussed the clinical, pathological and immunohistochemical findings of extrapulmonary small cell carcinoma of the liver and reviewed the relevant literature.

Tumor carcinóide de duodeno: relato de caso e revisão de literatura / Carcinoid tumor of the duodenum: case report and literature review

Os tumores carcinóides não são comuns e aqueles da área duodenopancreática evoluem lentamente, mas sua história natural não é bem conhecida. O objetivo deste trabalho é relatar o caso de um homem com um tumor no intestino delgado e seu tratamento

Evaluation of neuroendocrine and proliferative markers in prostatic adenocarcinomas

Certain marker studies have practical importance in the biology of prostate cancer. The purpose of this study was to determine whether the quantification of certain neuroendocrine and proliferative markers obtained during transurethral resection or prostatectomy, would help in the prognostic evaluation of prostatic adenocarcinomas. The present study was performed on samples obtained from two groups of patients with acinar type prostatic adenocarcinoma. Each group comprised 21 patients with Gleason scores =/> 7 [high-grade] and Gleason scores

Spindle cell carcinoma of breast with neuroendocrine differentiation / 中华病理学杂志

<p><b>OBJECTIVE</b>To describe the morphologic features and immunohistochemistry of spindle cell carcinoma of breast with neuroendocrine differentiation.</p><p><b>METHODS</b>Retrospective review of 2500 cases of breast carcinoma showed 5 cases (0.2%) with a predominance (> 80%) of spindle cell component. Amongst the 5 cases studied, 2 represented intraductal spindle cell carcinoma and 3 represented invasive spindle cell carcinoma. The paraffin sections were stained with hematoxylin and eosin, alcian blue, periodic acid-Schiff and reticulin stain. Immunohistochemical studies for AE1/AE3, CEA, EMA, CK7, 34betaE12, NSE, synaptophysin, chromogranin A, Leu-7, vimentin, S-100, SMA, calponin, estrogen receptor, progesterone receptor, c-erbB2, E-cadherin, Ki-67 and p53 were also carried out. Follow-up information was available in 4 of the 5 cases.</p><p><b>RESULTS</b>The mean age of the patients was 68 years. Histologically, all tumors were predominantly composed of elongated spindle cells. Three of these cases also contained tumor cells with vacuolated cytoplasm, alcian blue-positive tumor cells were observed in 4 cases. Immunohistochemically, the spindle tumor cells in all cases expressed AE1/AE3, CEA, EMA, E-cadherin and synaptophysin. CK7 was positive in 4 cases, NSE in 3 cases, chromogranin A and Leu-7 in 2 cases. Estrogen receptor was expressed in 4 cases and progesterone receptor in 2 cases. Overexpression of c-erbB2 oncoprotein was detected in only 1 case. Vimentin was focally positive in 1 case. Two cases of intraductal spindle cell carcinoma and 1 of the 3 cases of invasive spindle cell carcinoma were classified as neuroendocrine carcinoma of spindle cell type, while the remaining 2 cases of invasive spindle cell carcinoma were considered as metaplastic carcinoma with neuroendocrine differentiation. Amongst the 4 patients with follow-up information available, 3 were still alive 24 to 58 months after the initial diagnosis. One patient died within 27 months of diagnosis.</p><p><b>CONCLUSIONS</b>The presence of spindle tumor cells and sometimes intracytoplasmic mucin are useful morphologic clues in diagnosing spindle cell carcinoma of the breast with neuroendocrine differentiation. Intraductal neuroendocrine spindle cell carcinoma needs to be distinguished from usual ductal hyperplasia and intraductal papilloma. On the other hand, invasive spindle cell carcinoma with neuroendocrine differentiation needs to be distinguished from spindle cell myoepithelioma, malignant melanoma and sometimes soft tissue neoplasm.</p>

Carcinoid syndrome: diagnosis and medical management

Gastro-intestinal carcinoids are slow growing tumors arising from enterochromaffin or Kulchitsky cells. Their clinical presentation depends on what combination of bioactive substances is secreted. Midgut carcinoid can present with the carcinoid syndrome in the presence of liver metastases. Its most typical clinical manifestations include cutaneous flushing and diarrhea. A nonspecific biochemical tumor marker for carcinoid tumors is serum chromogranin A and a specific marker for the carcinoid syndrome is the increased urinary excretion of 5-hydroxy indole acetic acid (5-HIAA). Localizing studies in carcinoid tumors/syndrome are: transabdominal ultrasonography (US), endoscopy, endoscopic US, videocapsule endoscopy, computerized tomography, magnetic resonance imaging, selective abdominal angiography, 111In-pentetreotide scintigraphy (and intraoperative radionuclide probe), 123I (131I)-metaiodobenzylguanidine (MIBG) scintigraphy, bone scintigraphy and 11C-5-HT positron emission tomography (PET). Therapies for carcinoid tumors/syndrome are: surgery, somatostatin analogs, interferon-alpha, radiotherapy, liver dearterialization, liver (chemo, or radio)-embolization, alcohol sclerotherapy of liver metastases, radiofrequency ablation of liver metastases, cryosurgery of liver metastases, occasionally liver transplantation, radiotherapy-coupled somatostatin analogs, 131I-MIBG and occasionally chemotherapy.

Diferenciação neuroendócrina dos mesoteliomas pleurais / Neuroendocrine differentiation in pleural mesotheliomas

Introdução: o termo neuroendócrino tem sido usado para definir células que secretam seus produtos de maneira regulada oudirigida em resposta a estímulos específicos. O sistema neuroendócrino inclui neurônios, células endócrinas e células imunes, compartilhando um fenótipo comum, caracterizado pela expressão de diversos marcadores. O objetivo do presente estudo foi determinar por imuno-histoquímica, o grau de diferenciação neuroendócrina em mesoteliomas pleurais por meio da sensibilidade múltipla em paralelo dos marcadores tumorais cromogranina A e enolase neurônio-específica (NSE). Metodologia: estudo secundário resultante da revisão não sistemática. Análise de dados primários não publicados de 16 pacientes com mesotelioma pleural maligno. A técnica imuno-histoquímica utilizada foi peroxidase-anti-peroxidase. Os marcadores utilizados foram: cromogranina A; NSE; queratina, vimentina, desmina, actina muscular e proteína S100. Cálculo da sensibilidade isolada de cada marcador e da sensibilidade para diferenciação neuroendócrina com os marcadores NSE e cromogranina A na combinação múltipla em paralelo. Resultados: pacientes eram 11 homens (média de idade, 63 anos) e 5 mulheres (média de idade, 47 anos). Dos casos, 81 (13/16) eram do tipo histológico epitelial e 19 (3/16) do tipo bifásico. Sensibilidade isolada dos marcadores: queratina 100, vimentina 94, desmina 56, NSE 25, cromogranina A 31, proteína S100 31 e actina muscular 0. Sensibilidade para diferenciação neuroendócrina de 55,9 com NSE e cromogranina A usados como testes múltiplos em paralelo. Conclusão: na prática clínica a expressão de marcadores neuroendócrinos em mesoteliomas pleurais conduz a possibilidade dessas neoplasias expressarem maior quimiossensibilidade e de serem úteis para o diagnóstico diferencial com outros tipos de neoplasias na pleura