PKA drives paracrine crisis and WNT4-dependent testis tumor in Carney complex

ABSTRACTLarge Cell Calcifying Sertoli Cell Tumors (LCCSCTs) are among the most frequent lesions occurring in Carney complex (CNC) male patients. Although they constitute a key diagnostic criterion for this rare multiple neoplasia syndrome resulting from inactivating mutations of the tumor suppressor PRKAR1A leading to unrepressed PKA activity, the LCCSCT pathogenesis and origin remain elusive. Mouse models targeting Prkar1a inactivation in all somatic populations or separately in each cell type were generated to decipher the molecular and paracrine networks involved in the CNC testis lesion induction. We demonstrate that Prkar1a mutation is required in both stromal and Sertoli cells for the occurrence of LCCSCT. Integrative analyses comparing transcriptomic, immunohistological data and phenotype of mutant mouse combinations led to understand the human LCCSCT pathogenesis and demonstrated unprecedented PKA-induced paracrine molecular circuits in which the aberrant WNT4 signal production is a limiting step in shaping intratubular lesions and tumor expansion both in mouse model and human CNC testes.

Large Cell Calcifying Sertoli Cell Tumor with Macrocalcification in a Partially Resected Testis

Large cell calcifying Sertoli cell tumors (LCCSCTs) are extremely rare, with less than 100 tumors being described to date. Most of the tumors are benign with a few malignant cases, and aggressive behavior is infrequent. These tumors are a type of Sertoli cell tumor, and these tumors comprise less than 0.3% of all testis tumors in Saudi Arabia. They usually occur in boys and young adults and can affect one or both testicles in multifocal form causing microcalcifications. A 28-year-old male visited our hospital with left testis pain. Physical examination of the scrotum revealed that both testicles were normal sized with no palpable mass. Ultrasonography evaluation revealed grade 3 left varicocele and an incidental 9 mm calcified mass in the right testicle, which was further confirmed by MRI. Partial orchiectomy was performed. Clinical data, radiological studies, and morphological and immunohistochemical characteristics were analyzed.

Case Report on Sertoli Cell Tumor of Ovary

A 33 years old lady presented with history of irregular menstrual cycle followed by menorrhagia. USG revealed left ovarian solid mass but all tumor markers were within normal range. A solid mass on left sided ovary was found on laparotomy. Histopathological examination of the mass showed well differentiated sertoli cell tumor. Tumors of the stroma (Leydig cells) and/or sex cords (Sertoli cells) represent approximately 8% of ovarian tumors and develop from the connective tissue (respectively, interstitial and nurse cells) of the ovary. Because these cells participate in ovarian hormonal function, most of the sex-cord or stromal tumors are able to secrete hormones (estrogens, androgens, corticoids), which explains the hormonal dysfunctions associated with these tumors. Their prognosis are difficult to establish; some of the tumors are almost always benign (Sertoli cell tumors, Leydig cell tumors), whereas others are malignant but with more-or-less delayed local-regional or metastatic relapses.Bangladesh J Obstet Gynaecol, 2016; Vol. 31(1) : 54-56