Immunohistochemical Markers in the Differential Diagnosis of Melanoma and Nevus in Humans

SUMMARY: Immunohistochemistry allows in situ detection of cell and extracellular components through specific antibodies. The objective was to compare the immunohistochemical expression patterns of the S-100, HMB-45 and MART-1 proteins for differential diagnosis of malignant melanoma and melanocytic nevus in human skin biopsies. Thirty-nine biopsies of human tissue were used. They were divided into two groups: 19 in malignant melanoma and 20 in melanocytic nevi. Next, the samples were fixed with paraformaldehyde and processed following the protocol for inclusion. Then, immunohistochemical staining was performed. Finally, the histological and qualitative analysis of the samples was carried out. S-100, HMB-45, and MART-1 markers showed positive immunoreaction in melanoma biopsies. HMB-45 marker was generally present with weaker expression than S-100 and MART-1 in melanocytic nevus biopsies. No expression pattern was observed which specifically associates one or more markers with some types of histopathological diagnosis. Immunohistochemistry is fundamental in differential diagnosis of melanomas and melanocytic nevi. However, there is no antibody or set of antibodies which allows unequivocal diagnosis between melanoma and nevus. It is therefore necessary to analyze with care the expression pattern and location of the lesion using standard morphological characteristics.

RESUMEN: La inmunohistoquímica permite la detección in situ de componentes celulares y extracelulares a través de anticuerpos específicos. El objetivo de nuestro estudio fue comparar los patrones de expresión inmunohistoquímica de las proteínas S-100, HMB-45 y MART-1 para el diagnóstico diferencial de melanoma maligno y nevo melanocítico en biopsias de piel humana. Se utilizaron treinta y nueve biopsias de tejido humano, las que fueron divididas en dos grupos: 19 en melanoma maligno y 20 en nevos melanocíticos. A continuación, las muestras se fijaron con paraformaldehído y se procesaron siguiendo el protocolo convencional para su inclusión. Luego, se realizó la tinción inmunohistoquímica. Finalmente, se realizó el análisis histológico y cualitativo de las muestras. Los marcadores S-100, HMB- 45 y MART-1 mostraron inmunorreacción positiva en biopsias de melanoma. El marcador HMB-45 estuvo generalmente presente con una expresión más débil que S-100 y MART-1 en biopsias de nevo melanocítico. No se observó ningún patrón de expresión que asocie específicamente uno o más marcadores con algunos tipos de diagnóstico histopatológico. La inmunohistoquímica es fundamental en el diagnóstico diferencial de melanomas y nevos melanocíticos. Sin embargo, no existe ningún anticuerpo o panel de anticuerpos que permita un diagnóstico inequívoco entre el melanoma y el nevo. Por tanto, es necesario analizar con cuidado el patrón de expresión y la localización de la lesión utilizando características morfológicas estándar.

Comparison of core needle biopsy and surgical specimens for accurate evaluation of hormonal receptors status and molecular subtypes of breast cancer / 中国肿瘤临床

Objective:To explore concordance between preoperative core needle biopsy(CNB)and resection specimen(RS)in evaluat-ing biomarkers and molecular subtypes with immunohistochemical method.Methods:A retrospective study was performed on 324 breast cancer patients who underwent modified radical mastectomy at the Tianjin Medical University Cancer Institute and Hospital be-tween August 2015 and November 2016.All patients who had received neoadjuvant systemic therapy were excluded.The aim of this analysis was to report concordance between CNB and surgical specimens in evaluating biomarkers,such as ER,PR HER-2,Ki-67,and molecular subtypes.Results:There was concordance between estrogen receptor(ER)assessment on CNB and RS in 94.1%(305/324) of the patients(κ=0.84).Concordance of the progesterone receptor(PR)and the human epidermal growth factor receptor 2(HER-2) assessments were observed in 90.7%(294/324,κ=0.76)and 61.1%(198/324,κ=0.38)patients,respectively.Evaluation of Ki-67 re-vealed an accordance rate of 86.7%(281/324,κ=0.34),and the concordance for immunohistochemistry detection for assessing breast cancer(BC)molecular subtypes was 73.4%(91/124,κ=0.64).Conclusions:Although CNB showed good accuracy for evaluating hormon-al receptor status and BC molecular subtypes,its evaluation of HER-2 and Ki-67 statuses was less accurate than other biomarkers. Therefore,we should combine immunohistochemical results with both CNB and RS samples in order to improve accuracy when diag-nosing molecular subtypes.Moreover,improved diagnoses can provide the basis for more effective systemic therapies.

A prognostic nomogram for ER/PR+ and HER2- breast cancer patients based on classical immunohistochemical index / 中国肿瘤生物治疗杂志

@# Objective: To modify traditional prognostic model for patients with ER/PR+, HER2- breast cancer to meet the actual requirements in current clinical practice. Methods: 335 patients with ER/PR+, HER2- breast cancer, who were admitted in Department of Breast Surgery, Shanghai Huangpu Center Hospital from January 2009 to December 2009, were enrolled in this study. 97 variables were incorporated into the model, using SCAD variable selection method, after fully considering whether covariates existing a log-linear relationship, reasonable determination of the cut-off value of the covariates in non-logarithmic linear relationship (piecewise linear relationship) and collinear and interaction, then we set up a new Cox regression prognostic model for traditional ER/PR+, HER2-type breast cancer patients with traditional immunohistochemical indicators, and further establish its nomogram model. On this basis, a nomogram of the survival probability of 1-, 3-, and 5- years after surgery was established; The discrimination and calibration of model were compared to evaluate the predictive ability of the model. Results: The Cox regression model shows that the prognosis of patients are associated with the histologic grade, lymph node metastasis, Ki67, PR and age etc. Among them, the histologic grade and lymph node metastasis have log-linear relationship with prognosis; Ki67, PR and age have non-log-linear relationship with prognosis and the reasonable cut-off values are Ki67(60%)，PR（20%）and age（55 years old） . Area under the receiver operating characteristic (ROC) curve（AUC）of this Cox model for 1-, 3- and 5- year survival after surgery are all above 0.85, indicating high discrimination. The Grønnesby-Borgan goodness-of-fit test statistics of this model is 1.37 with P>0.05, indicating good calibration. Conclusion: The modified nomogram.could accurately, directly and effectively predict the survival probability of patients, which may exert good guidance for the clinical practice for patients with breast cancer.

Tumor de las células de la granulosa: importancia de la inmunohistoquímica en el diagnóstico

Se presenta un caso de una paciente joven de 30 años quien consultó por trastornos menstruales y dolor abdominal de evolución de 1 año. Se le diagnóstico una tumoración de ovario poco frecuente como son los tumores de las células de la granulosa por medio de marcadores de inmunohistoquímica.

It is presented a case of a young woman who had menstrual problems and abdominal pain since one year ago. It was diagnosed an uncommon ovarian tumor such as tumor of granulosa cells using immunohistochemical markers.

Atypical (Symplastic) Leiomyoma A case report.

Atypical, bizarre, symplasmic (symplastic), or pleomorphic leiomyoma contains bizarre tumor cells with variation in size and shape, hyperchromatic nuclei, giant cells and occasional multinucleated giant cells but no coagulative necrosis or increased mitotic activity. Mitotic counts higher than 10/10hpf in such a tumor indicates a high malignant potential smooth muscle tumor (leiomyosarcoma). Bizarre leiomyoma closely mimics leiomyosarcoma. We report a case of 31 years old, nulliparous woman who presented with a history of infertility. On examination she was found to have uterine fibroid of 28 weeks size over a period of 5 years. She was diagnosed to have fibrobid clinically and on ultrasonographic examination. Hence, a myomectomy was performed. Histomorphological features are of atypical (Symplastic) leiomyoma which closely mimics leiomyosarcoma and immunohistochemical markers are certainly of help to exclude malignancy in case of dilemma.

The Diagnostic Usefulness of HMGA2, Survivin, CEACAM6, and SFN/14-3-3 delta in Follicular Thyroid Carcinoma

BACKGROUND: Follicular thyroid carcinoma (FTC) is the second most common thyroid malignancy and its differential diagnosis includes follicular adenoma (FA) and adenomatous goiter (AG). Several ancillary markers have been suggested to aid in the diagnosis of FTC, but the successful use of these methods still needs to be validated. METHODS: In the present study, we verified the immunoexpression of HMGA2, CEACAM6, survivin, and SFN/14-3-3 delta in lesions including 41 AGs, 72 FAs, and 79 FTCs. We evaluated their diagnostic usefulness, combined with galectin 3, Hector Battifora mesothelial 1 (HBME1), cytokeratin 19, and cyclin D1, in diagnosing FTC. RESULTS: The expressions of HBME1 (65.8%) and HMGA2 (55.7%) were significantly higher in FTCs than in FAs and AGs (p<.001 and p=.005, respectively). HBME1 was the only marker that was more frequently expressed in FTCs than in FAs (p=.021) and it was more frequently expressed in follicular neoplasms than in AGs (p<.001). Among the novel markers, the combination of HMGA2 and HBME1 showed the highest sensitivity (72.2%) and specificity (76.1%) for diagnosing FTC. CEACAM6, survivin, and SFN/14-3-3 delta were barely expressed in most cases. CONCLUSIONS: Our present results show that only HMGA2 can be beneficial in differentiating FTC using the novel markers.

Las cadherinas en el diagnostico histopatológico y pronostico del carcinoma de células renales / The cadherins in the histopathology diagnosis and prognosis of renal cell carcinoma

El carcinoma de células renales es el cáncer renal más común en el adulto. Se describen 5 tipos histológicos principales, que, en general, muestran al microscopio óptico características que permiten diagnosticarlos. Sin embargo, el solapamiento morfológico observado entre los diferentes tipos y la heterogeneidad histológica dentro del mismo tumor, continúan generando problemas en su clasificación. Algunos marcadores inmunohistoquímicos son empleados en el diagnóstico diferencial de estos carcinomas, pero tienen sus limitaciones. En el presente trabajo, se hizo una revisión de varios estudios, en los que se identificaron alteraciones en la expresión de algunas cadherinas en tejidos renales y líneas celulares con carcinoma de células renales. Estas alteraciones estuvieron asociadas con diferentes estados del desarrollo y progresión del tumor, y sirvieron para predecir el comportamiento neoplásico. Incrementar nuestro conocimiento en este campo, contribuiría al hallazgo de marcadores mucho más específicos para el diagnóstico y pronóstico de estos tumores.

Renal cell carcinoma is the most common adult renal cancer. Five main histological types are described, that in general display characteristic light microscopic features that lead to a correct diagnosis. However, the morphologic overlap between tumors and the histologic heterogeneity within a single tumor continue to create problems in the classification. Some immunohistochemical markers are used in the differential diagnosis of these carcinomas, but they have limitations. In the present work, a review of several studies was made, in which alterations in expression of some cadherins in renal tissue and cell lines with renal cell carcinoma were identified. These alterations were associated with different stages of tumor development and progression, and used to predict the neoplastic behaviour. To increase our knowledge in this field, will contribute to find more specific markers for the diagnosis and prognosis of these tumors.

Treatment Outcomes of Anorectal Melanoma

PURPOSE: An anorectal melanoma (AM) is a very rare tumor. However, sufficient data supporting effective surgical options for the disease do not exist. This retrospective review aimed to analyze treatment outcomes for an AM. METHODS: From June 1999 to December 2008, we retrospectively reviewed a prospectively collected consecutive series of 19 patients who had undergone a surgical resection for an AM at a single institute. Surgical method and clinicopathological factors were analyzed. RESULTS: The median age was 61.4 years (range, 46 to79 years). Main symptoms were an anal mass, hematochezia, perianal pain, tenesmus, fecal incontinence, and bowel habit change. The average duration of symptoms before diagnosis was 7.8 months (range, 1 to 36 months). S-100 and HMB-45 were positive in all patients, even in non-melanin pigmentation. There were 12 abdominoperineal resections (APRs) and 7 wide local excisions (WEs). The APR showed longer overall survival when compared with the WE (64.1 months vs. 10.9 months, P < 0.001). No patients who underwent a WE survived more than 13 months. CONCLUSION: A high index of suspicion is necessary to establish the diagnosis for an AM in patients with anal symptoms, and S-100 and HMB-45 can be useful markers for an AM. Even with the small number of cases and the short follow-up, our data suggest that an APR for an AM may provide longer survival than a WE.