Poorly differentiated (PD) thyroid carcinomas lie both morphologically and behaviorally between well-differentiated and undifferentiated (anaplastic) carcinomas. Following the original description of this entity, different diagnostic criteria have been employed, resulting in wide discrepancies and confusion among pathologists and clinicians worldwide. To compare lesions occurring in different geographic areas and the diagnostic criteria applied in those countries, we designed a study with a panel of internationally recognized thyroid pathologists to develop consensus diagnostic criteria for PD carcinomas. Eighty-three cases were collected from Europe, Japan, and the United States, and circulated among 12 thyroid pathologists. Diagnoses were made without any knowledge of the clinical parameters, which were subsequently used for survival analysis. A consensus meeting was then held in Turin, Italy, where an agreement was reached concerning the diagnostic criteria for PD carcinoma. These include (1) presence of a solid/trabecular/insular pattern of growth, (2) absence of the conventional nuclear features of papillary carcinoma, and (3) presence of at least one of the following features: convoluted nuclei; mitotic activity >or=3 x 10 HPF; and tumor necrosis. An algorithmic approach was devised for practical use in the diagnosis of this tumor.

The efficacy of fertility-sparing treatment with a high-dose of MPA for EC and AH was proven by this prospective trial. Even in responders, however, close follow-up is required because of the substantial rate of recurrence.

The relationship between histologic type and survival of 258 thyroid malignancies has been analysed. A new clinicopathologic entity, poorly differentiated carcinoma of the thyroid, is proposed. Papillary and follicular carcinomas of the thyroid showed no significant difference in survival rates. Both tumors were histologically separated into well differentiated and poorly differentiated carcinomas, so that thyroid cancer, deriving from follicular cells, was divided into well differentiated, poorly differentiated, and anaplastic carcinomas. The characteristic histology of poorly differentiated carcinoma was the presence of solid, trabecular and/or scirrhous patterns. Poorly differentiated carcinoma was found in 13.6% of all thyroid malignancies, and its prognosis was worse than that of well differentiated carcinoma. The differences of survival rates among well differentiated, poorly differentiated and anaplastic carcinomas were statistically significant. Prognostic data support the suggestion that the clinicopathologic entity of poorly differentiated carcinoma is of value in determining management and survival of thyroid cancer patients.

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L-Carnitine is an essential component of mitochondrial fatty acid ␤-oxidation and plays a pivotal role in the maturation of spermatozoa within the male reproductive tract. Epididymal plasma contains the highest levels of L-carnitine found in the human body, and initiation of sperm motility occurs in parallel to L-carnitine increase in the epididymal lumen. Using a specific carrier, epididymal epithelium secretes L-carnitine into the lumen by an active transport mechanism; however, the structure-activity relationship comprising the carnitine-permeation pathway is poorly understood. We discovered a novel carnitine transporter (CT2) specifically located in human testis. Analyzing the primary structure of CT2 revealed that it is phylogenetically located between the organic cation transporter (OCT/OCTN) and anion transporter (OAT) families. Hence, CT2 represents a novel transporter family. When expressed in Xenopus oocytes, CT2 mediates the high affinity transport of L-carnitine but does not accept mainstream OCT/ OCTN cationic or OAT anionic substrates. We synthesized and tested various carnitine-related compounds and investigated the physicochemical properties of substrate recognition by semi-empirical computational chemistry. The data suggest that the quaternary ammonium cation bulkiness and relative hydrophobicity be the most important factors that trigger CT2-substrate interactions. Immunohistochemistry showed that the CT2 protein is located in the luminal membrane of epididymal epithelium and within the Sertoli cells of the testis. The identification of CT2 represents an interesting evolutionary link between OCT/OCTNs and OATs, as well as provides us with an important insight into the maturation of human spermatozoa.

Summary Matrix metalloproteinases play a crucial role in tumour invasion and mestasis. Matrilysin (MMP-7) has been shown to correlate with nodal or distant metastasis in colorectal carcinomas; however, its implication in early invasive colorectal carcinomas has not been determined. This study was undertaken to clarify the association of matrilysin expression with clinicopathologic parameters in early invasive colorectal carcinomas. 38 early invasive colorectal carcinomas treated by local excision or radical surgery were examined. Tumour budding was evaluated as the number of dedifferentiation units along the entire invasive margin. Matrilysin protein levels were determined using immunohistochemical study. Univariate analysis showed that matrilysin expression alone was significantly associated with distant metastasis (P = 0.0339), and both tumour budding and matrilysin expression were significantly associated with adverse outcome (P = 0.0005, 0.0341). Histological differentiation, vessel invasion, and depth of invasion were not significantly associated with either distant metastasis or adverse outcome. Multivariate analysis confirmed that tumour budding and matrilysin expression were independently associated with adverse outcome, although the significance of matrilysin expression was marginal (P = 0.0488). Tumour budding at the invasive margin and matrilysin expression are more useful in identifying high-risk groups for adverse outcome in patients with early invasive colorectal carcinomas.

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Objective: To evaluate the sensitivity and specificity of endometrial cytology obtained by intrauterine sample using a descriptive reporting format for endometrial cytological diagnosis. Study Design: 10,152 consecutive endometrial scrapings obtained in 13 different Japanese hospitals were analyzed. Cytological results were classified as ‘negative for malignancy’, ‘atypical endometrial cells’ (ATEC), ‘endometrial hyperplasia’, ‘atypical endometrial hyperplasia’ or ‘malignant tumor’. ATEC was subclassified as ‘ATEC, of undetermined significance’ (ATEC-US) and ‘ATEC, cannot exclude atypical endometrial hyperplasia or more’ (ATEC-A). Cytological results were compared with the histological diagnosis as a gold standard. When the cytological result was ‘negative for malignancy’ and there was no subsequent histological examination, the case was considered a true negative when the endometrium was assessed as normal on transvaginal ultrasonography and there was no abnormal uterine bleeding. Results: 1,083 cases in which histology was not performed, 557 cases of ‘unsatisfactory specimen’ and 76 cases of ATEC-US were excluded. In the remaining 8,436 cases, the sensitivity and specificity, positive predictive value and negative predictive value for detecting atypical endometrial hyperplasia or malignant tumors were 79.0 and 99.7, 92.9 and 98.9%, respectively. Conclusion: The current diagnostic standards for endometrial cytology in Japan were established. Specificity is satisfactory for excluding cancer or precancerous diseases.