Gradual and synergistic correlation of tumor thickness and histological grade in penile invasive carcinomas.

Histological grade and depth of invasion are among the best outcome pathological predictors in penile cancer. The TNM system is based on a combination of both for some stages. It is assumed that high-grade and deep tumors carry the worst prognosis, and the opposite occurs with superficial and low-grade neoplasms. However, there is no systematic evaluation of the phenomenon. We studied 147 patients from the Hospital de Oncologia - Instituto Mexicano del Seguro Social (period 2000 to 2013). They were treated by total or partial penectomies. Lymph node involvement was evaluated by bilateral inguinal node dissection (126 cases) or ultrasonography (21 cases). Tumor thickness was measured in mm from tumor surface to deepest invasion point, using a cut-point for superficial (≤10 mm) vs deep (>10 mm) tumors. Histological grade was from 1 to 3 according to WHO and AFIP criteria and considering G1 and G2 as low-grade and G3 as high-grade. Average age was 62 (26-98) years old. Tumor thickness mean was 15 mm (2-30 mm). G1, G2 and G3 tumors corresponded to 19 (13 %), 48 (33 %), and 80 (54 %) cases, respectively. Follow-up ranged from 10 to 82 months (median: 57 months). Fifty-three (36 %) patients died of disease. There was an overall correlation of tumor thickness and grade in most of the cases. Low-grade tumors were encountered in 92 % (12/13 cases) of superficial tumors. Deep tumors showed high-grade in 75 % of cases (73/97 cases). Superficial tumors with low histological grade had negative inguinal nodes and no mortality whereas deep tumors showing high histological grade were associated with high metastatic risk to lymph nodes (62/73 cases) and mortality (52/73 cases). Out of 24 deep tumors with low histological grade, seven had nodal spread (29 %) but only one died of disease. No outcome difference was found in HPV associated vs HPV independent tumors. Tumor thickness and grade are important synergistic and predictive pathological factors in relation to prognosis.

Preneoplasia of the Breast and Molecular Landscape.

The current model of human breast cancer progression proposes a linear multi-step process which initiates as flat epithelial atypia (FEA), progresses to atypical ductal hyperplasia (ADH), evolves into ductal carcinoma in situ (DCIS) and culminates in the potentially lethal stage of invasive ductal carcinoma. FEA commonly coexists with well-developed examples of ADH, low-grade DCIS, lobular neoplasia and tubular carcinoma. These findings and those of recent genetic studies suggest that FEA is a neoplastic lesion that may represent a precursor to or the earliest morphologic manifestation of ductal carcinoma in situ. At the same time, many of the genomic changes of ADH are also shared by common sporadic breast cancer, consistent with a high risk for future development of metachronous breast cancer.

Metastasis of melanoma to the gastrointestinal tract. Report of three cases / Metástasis de melanoma al tracto gastrointestinal. Reporte de tres casos

Background: Cutaneous melanoma is one of the most common malignancies to metastasize to the gastrointestinal tract. Presence of tumor metastasis is an important prognostic factor. Despite clinical advances, the five-year survival rate of patients with stage IV malignant melanoma is only about 14%. We present three clinical cases with metastasis of cutaneous melanoma. Clinical cases: Man 68 years old and woman 55 years old, with colon metastasis; and man 75 years old with metastasis to the small intestine. All of them underwent resection alone when they presented gastrointestinal symptoms and they obtained relief after it. Two patients had initial cutaneous lesions with Breslow´s thickness < 2 mm. The three patients died months after the surgery. Conclusion: Meticulous attention to patients with prior history of cutaneous melanoma who present with subtle gastrointestinal symptoms is highly recommended.

Introducción: el melanoma cutáneo es una de las neoplasias malignas que con mayor frecuencia metastatiza al tracto gastrointestinal. La presencia de metástasis es un factor pronóstico importante. A pesar de los avances clínicos, la supervivencia libre de enfermedad a 5 años en pacientes con melanoma cutáneo en estadio clínico IV es únicamente de 14%. Se presentan tres casos clínicos, con melanoma cutáneo metastásico a intestino. Casos clínicos: hombre de 68 años y mujer de 55 años de edad, con metástasis en colon; hombre de 75 años de edad con metástasis a intestino delgado. Cuando presentaron síntomas grastrointestinales, fueron tratados únicamente con cirugía, con alivio de los síntomas iniciales. Dos pacientes tenían diagnóstico previo de melanoma cutáneo, con espesor de Breslow < 2 mm. Los tres pacientes fallecieron meses después de la cirugía. Conclusión: se recomienda prestar atención especial a pacientes con historia previa de melanoma cutáneo que presenten síntomas gastrointestinales inespecíficos.

Micropapillary Cervical Adenocarcinoma: A Clinicopathologic Study of 44 Cases.

Micropapillary adenocarcinoma has been reported as an aggressive variant of adenocarcinoma in several organs, where it is associated with poor clinical outcome. This study reports the clinicopathologic features and outcomes of cervical adenocarcinomas with a micropapillary component (micropapillary cervical adenocarcinomas); this represents the largest reported study of these neoplasms. The study comprised 44 cervical adenocarcinomas of usual (human papillomavirus-related)-type (84%), mucinous, not otherwise specified (4.5%), gastric-type (4.5%), endometrioid (4.5%), and adenosquamous carcinoma (2%). The micropapillary component comprised >50% of the neoplasm in 34 cases (77%) (group 1), and 10% to 50% in 10 cases (23%) (group 2). Lymph node metastasis was present in 41 of 44 (93%) cases and typically the nodal tumor retained a prominent micropapillary morphology. Follow-up ranged from 7 to 123 months (mean, 65.9 mo). Seventeen of 44 (38.6%) patients had no evidence of disease on follow-up, 6/44 (13.6%) were alive with disease, and 21/44 (47.7%) died of disease. There were no survival differences between group 1 and group 2. On univariate analysis, lymph node metastasis (P=0.0015), lymphovascular space invasion (P=0.002), parametrial involvement (P=0.03), and depth of stromal invasion (P=0.045) were related to tumor recurrence. On multivariate analysis, lymph node metastasis (P=0.001), and extent of lymphovascular space invasion (P=0.027) were significant independent predictors of tumor recurrence. Our study shows that a micropapillary component in cervical adenocarcinoma may be associated with aggressive behavior and that a micropapillary architecture may occur within a variety of types of cervical adenocarcinoma.

HER2/neu, p53, MIB1 and PAX8 immunoexpression in Primary Serous Fallopian Tube Carcinomas / Determinación inmunohistoquímica de HER2/neu, p53, MIB1 y PAX8 en el Carcinoma Seroso Primario de la Trompa Uterina

Background. Carcinoma of the fallopian tube is a rare gynecological malignancy. A previous review of Primary Fallopian Tube Carcinoma (PFTC) from a multi-institutional study identified several poor prognosis indicators, including the depth of invasion, advanced stage disease, tumor grade and the presence of lymph node metastases. The detection of the malignant lesion at an early stage and the identification of biomarkers with prognostic significance are the major concerns of recent studies. Aims. In this study, we have investigated the immunohistochemical expression of 4 proteins in cases of low-grade (n:5) and high-grade (n:65) serous PFTC to determine their role in PFTC prognosis. Material and methods. HER2/neu, p53, PAX8 and MIB-1 were evaluated using immunohistochemistry on a tissue microarray of 70 serous PFTC and the expression was correlated to the following clinico-pathologic variants: age, grade, lymph node metastases, stage and survival. Results. HER2/neu oncoprotein overexpression was demonstrated in 20 of 65 (31%) high-grade serous fallopian tube carcinomas. p53 was demonstrated in more than 50% (3+) of the tumor in 59 (90.7%) high-grade serous FTCs, while eight cases (12%) were moderate or weakly positive (2+). The expression of PAX8 was positive in 55 (78.5%) cases, the remaining 15 (21%) cases being negative. The outcome of the disease for patients with tumors showing HER2/neu overexpression was worse (p:0.0001). p53, MIB-1 or PAX8 failed to have a predictive value in disease outcome. Conclusion. The potential prognostic relevance of HER2/neu in tubal cancer and its potential role in the selection of patients for targeted therapy should be investigated further (AU)

Introducción. El carcinoma de la trompa uterina (TU) es una neoplasia poco frecuente del tracto ginecológico. Una revisión previa de los carcinomas primarios de la TU, en un estudio multiinstitucional, identificó varios factores de mal pronóstico, incluyendo profundidad de invasión, estadio avanzado, grado histológico y presencia de ganglios linfáticos metastásicos. Detectar esta neoplasia en estadios tempranos e identificar biomarcadores con significado pronóstico ha sido el objetivo de los últimos estudios. Objetivos. En este estudio investigamos la expresión de 4 proteínas a través de inmunohistoquímica en 70 casos de carcinomas serosos de la TU (CSTU) (5 de bajo grado [BG], y 65 de alto grado [AG]) para determinar su papel pronóstico. Material y métodos. Se evaluó el estado de HER2/neu, p53, PAX8 y MIB-1 en matrices de tejidos, y se correlacionó con las siguientes variantes clinicopatológicas: edad, grado, metástasis ganglionares, estadio y supervivencia. Resultados. Demostramos la sobreexpresión de la oncoproteína HER2/neu en 20 de 65 (31%) CSTU AG. p53 se expresó en más de 50% (3+) del tumor en 59 (90,7%) casos, mientras que en 8 casos (12%), la expresión fue moderada o débil (2+). El PAX8 se expresó en 55 (78,5%) casos, y los otros 15 casos (21%) fueron negativos. El pronóstico de las pacientes cuyos tumores sobreexpresaron el HER2/neu fue más adverso (p=0,0001). p53, MIB-1 o PAX-8 no tuvieron un papel predictivo en el pronóstico de la enfermedad. Conclusiones. La relevancia del papel pronóstico de la sobreexpresión del HER2/neu en el CSTU, así como la posibilidad de seleccionar pacientes para recibir terapias dirigidas deben ser investigadas en más estudios (AU)

[Perception of health and safety risks among workers pathology laboratories]. / Percepción de las medidas de seguridad y salud en trabajadores de laboratorios de patología.

BACKGROUND: Health care workers are experiencing increasing numbers of occupational illnesses. Safety practices in anatomical pathology laboratories (APL) are crucial to prevent unnecessary exposures to both chemical and biological agents. METHODS: The main goal of this study was to determine if pathologists perceptions and actual practice mirror regulatory guidelines. Current available recommendations for APL were reviewed and used to construct an online survey distributed to pathologists. The survey was completed by 121 participants. RESULTS: Eighty-seven (72 %) of respondents reported receiving inadequate safety training. Most pathologists (82 %) were not well-informed about biosafety practices. Sixty-three (52 %) participants felt that the risks of chemical and infectious disease exposures in the APL were low. Most respondents reported having a needle stick or cut (71 %). Eighty-six (71 %) of participants reported musculo skeletal problems. CONCLUSIONS: This study indicated that there is a need for improving training in anatomical pathology safety practices in Mexican laboratories as daily practices do not reflected current guidelines.

Introducción: Los trabajadores de la salud pueden padecer de numerosas enfermedades relacionadas con su ocupación. Las prácticas de seguridad (PS) en los laboratorios de anatomía patológica (LAP) son indispensables para prevenir las exposiciones innecesarias a los agentes químicos o biológicos en dicha área de trabajo. El objetivo fue evaluar el nivel de conocimientos de los patólogos con respecto a las PS. Se revisaron las regulaciones y recomendaciones actuales para las PS en los LAP y con esa información se elaboró un cuestionario que se envió por Internet a los participantes. Métodos: La evaluación fue realizada por 121 patólogos, de los cuales 87 (71 %) reportaron un entrenamiento inadecuado en PS. La mayoría de los encuestados (82 %) no tenían una idea clara del significado de las medidas o prácticas de seguridad en el LAP. Resultados: Un total de 63 (52 %) de los participantes consideraron que el riesgo de enfermedades secundarias a la exposición a sustancias químicas peligrosas y agentes biológicos era bajo. De los participantes (71 %) reportaron algún accidente con un agente punzocortante o cortante. De 86 encuestados (71 %) reportaron problemas musculoesqueléticos. Conclusión: En este estudio se manifestó que existe una necesidad de implementar programas de capacitación en prácticas de seguridad en los laboratorios de anatomía patológica del Instituto Mexicano del Seguro Social.

Metastatic ovarian tumors: a clinicopathologic study of 150 cases.

OBJECTIVE: To determine the frequency of metastatic ovarian tumors and to identify their clinicopathologic features. STUDY DESIGN: A total of 150 patients with pathologically confirmed metastatic ovarian carcinoma who were treated between 1995 and 2011 at the Mexican Oncology Hospital were identified by retrospective review. Clinicopathologic data were analyzed. RESULTS: Metastatic ovarian carcinoma accounted for 15.7% of all ovarian malignancies. The primary sites of nongynecologic tumors were the colon (30%), stomach (16%), appendix (13%), breast (13%), pancreas (12%), biliary tract (15%), and liver (4%). Gynecologic primary sites were the uterine cervix (4%) and the uterine body (23%). Primary malignancies were detected first in 66 patients (44%) and simultaneously with ovarian metastasis in 53 patients (35.3%). An ovarian mass was the first manifestation of disease in 20.6% of the cases. The patients ranged in age from 26 to 72 years (mean, 51). Krukenberg tumors were found in 35 patients (23%). The cut surfaces of the ovaries were solid in 68 patients, solid-cystic in 38, and multicystic in 44. CONCLUSION: Metastatic ovarian carcinomas are an important group of ovarian neoplasms, constituting 15.7% of all ovarian malignancies. Most of them arise from the gastrointestinal tract.

Ovarian dysgerminoma associated with fibrosarcoma: a case report.

A 35-year-old woman presented with abdominal pain and weight loss. Pelvic computed tomography showed a 15 cm mass in the left ovary. Grossly, the removed ovary was completely replaced by a solid tumor mass. On histological analysis (100 sections), the lesion showed the typical morphological features of dysgerminoma (20%) admixed with a major (80%) fibrosarcoma component. Tumors did not have well-demarcated boundaries with a close intermingling of both cell types. Despite surgery and combination chemotherapy, the disease progressed rapidly and the patient died of disease 18 months after diagnosis. Review of the literature showed that soft tissue sarcomas of several types may occasionally be associated with gonadal and extragonadal mixed germ-cell tumors or with spermatocytic seminoma of the testis. However, no previously published report of an ovarian fibrosarcoma associated with a pure dysgerminoma was found in the literature.

Florid lobular intraepithelial neoplasia with signet ring cells, central necrosis and calcifications: a clinicopathological and immunohistochemical analysis of ten cases associated with invasive lobular carcinoma.

BACKGROUND AND AIMS: In its most florid form, classic lobular intraepithelial neoplasia (LIN) proliferates to form a solid mass of tumor cells that fill and expand the duct within the terminal duct lobular unit lumen. Foci such as these can develop central necrosis and calcifications, detectable on mammograms. The immunohistochemical expression of E-cadherin has been found to be absent in all reported examples of LIN with necrosis. The occurrence of LIN composed entirely of signet ring cells with central necrosis is extraordinarily rare. METHODS: We described 10 of these cases to illustrate this uncommon morphologic pattern of LIN. The cases were encountered during routine clinical practice of the authors over a 5-year period at the Oncology Hospital of the Mexican Social Security Institute in Mexico City. Cases were comprised of several (>6) foci of LIN with signet ring cells as well as with comedo-type necrosis. RESULTS: Age of patients ranged from 45-75 years (mean age: 51.2 years). The indications for biopsy were calcifications (n = 7) and mass (n = 3) on mammograms. Luminal necrosis was seen in all ten cases and calcifications in seven cases. Eight cases had associated invasive carcinoma, including six lobular carcinomas and one composite carcinoma (lobular and ductal). All cases showed a lack of E-cadherin membrane staining and a diffuse cytoplasmic immunoreactivity for high molecular weight keratin, positivity for estrogen receptors and progesterone receptors was present in 9/10 and 8/10 of cases, respectively. CONCLUSIONS: LIN composed entirely of signet ring cells can develop macro-acini, central necrosis and calcifications. These cases are frequently associated with invasive lobular carcinoma at the time of initial presentation.