Juvenile granulosa cell tumor of the ovary: A comprehensive clinicopathologic analysis of 15 cases.

OBJECTIVE: Juvenile granulosa cell tumor(JGCT) is an uncommon ovarian sex-cord stromal tumor, with diverse clinical, radiological and histopathologic features. The present study describes the clinicopathological and histomorphological spectrum of JGCTs, and highlights the key differentiating features from its mimics. METHODS: A retrospective analysis of all cases reported as JGCTs during 2011-19 (8 years) was performed with detailed evaluation of clinical, histopathologic data and follow-up details. RESULTS: Of a total 115 GCTs reported during the study period, 15(13%) were reported as JGCTs. The mean age at presentation was 17 years. Abdominal pain and distension were the most common clinical presentations. Five patients were pre-menarchal with 3 exhibiting precocious puberty. Majority of tumors were unilateral(left>right), solid-cystic, ranging in size from 4 to 20 cm. Microscopically, macrofollicular architecture was most frequent (n = 12;80%). The tumor cells depicted variable nuclear pleomorphism, small distinct nucleoli and moderate-abundant pale eosinophilic-clear/vacuolated cytoplasm. Mitotic activity ranged from 1 to 10/10HPFs. Uncommon histopathologic features included microcystic and tubulo-cystic architecture, myxoid degeneration, bizarre tumor giant cells, hob-nailing of the tumor cells, intracytoplasmic hyaline globules, multifocal calcification and thick hyalinized blood vessels. Majority(n = 12;80%) presented in stage I. Surgical treatment included unilateral salpingo-oophorectomy without any adjuvant chemotherapy, bilateral salpingo-oophorectomy (BSO) and total abdominal hysterectomy with BSO with adjuvant BEP chemotherapy (Bleomycin, etoposide, cisplatin). CONCLUSIONS: JGCT is a rare ovarian tumor affecting young women and children with diverse histopathologic features. Despite an aggressive histopathology, these tumors have a good outcome, when diagnosed at an early stage.

Juvenile granulosa cell tumor of the testis: a case presenting as a small round cell tumor of childhood.

We describe the case of a testicular juvenile granulosa cell tumor (JGCT) in a 4-year-old boy. The highly undifferentiated appearance and robust mitotic activity of the neoplasm led to an initial impression of an aggressive, small round cell tumor of childhood. Immunocytochemical and ultrastructural studies excluded the usual members of that group, and led to the correct diagnosis. To our knowledge, this is the oldest reported patient to present with this tumor in the testis, and the first with clinical evidence of hormonal activity. The benign behavior of testicular JGCT mandates that it be distinguished from other, much more aggressive, neoplasms which it may resemble.

Establishment and characterization of a human ovarian granulosa tumor cell line (HSOGT).

We successfully established a novel ovarian granulosa tumor cell line (HSOGT). The tumor tissue of the ovary was derived from a 25 year-old Japanese woman under her consent. The cell line was maintained for over 14 months, subcultured more than 73 times, and had a population doubling time of 18.9 hours. Phase contrast microscopy displayed a pavement-like arrangement without contact inhibition. The chromosome number showed a wide distribution of aneuploidy and the mode was 83; many marker chromosomes were observed. The HSOGT was also successfully xenotransplanted into nude mice. The cell line produced estradiol and has preserved some characters of granulosa cells with stable growth in vitro. We firmly believe that this cell line will be a most useful tool for endocrinological investigation of human granulosa cells.

Extraovarian granulosa cell tumor.

A 54-year-old woman was admitted to our hospital complaining of postcoital bleeding. Sonography of the abdomen showed a 8.2 x 8.9 cm-sized solid heterogeneous mass occupying the cul-de-sac, which appeared to be in no way connected with the ovary. On exploratory laparotomy, the tumor mass protruded from the posterolateral retroperitoneum of the pelvic cavity and severely replaced the uterus and adnexa with the outer surface being grossly intact. It grossly measured 10 cm in maximal diameter. The histologic features closely resembled those of ovarian granulosa cell tumor. The primary extraovarian granulosa cell tumor is extremely rare such that in the English literature only 7 cases have been reported to date. Of those granulosa cell tumors are especially rare and only two cases have been reported to arise from retroperitoneum. We herein present a case of retroperitoneal granulosa cell tumor with special regard to differential diagnosis from other solid tumors with similar histology.

Parameters of differentiation and proliferation in adult granulosa cell tumors of the ovary.

We evaluated parameters of cell differentiation and proliferation to improve prognostication of ovarian adult granulosa cell tumors. Recurrent tumors (n = 10, REC group) and nonrecurrent tumors (n = 30, NED group) were compared in terms of cellular atypia, nuclear area, p53 overexpression, ploidy, DNA index, mitosis count, S-phase fraction, and nucleolar organizer region number and area per cell. Cellular atypia was significantly more frequent in REC than NED tumors (50% versus 13%; P = .03). Mean nuclear area was significantly larger in the REC than in the NED group (44 microm2 versus 36 microm2; P = .006). Mitotic count was significantly higher in REC than NED tumors (mean of 4.8 versus 1.7; P = .004). S-phase fraction and ploidy did not predict outcome: neither did nucleolar organizer region numbers and area per cell, or p53 overexpression. Cellular atypia and mitotic count may help in determining the prognosis of adult granulosa tumors of the ovary. The histochemical parameters evaluated did not provide additional information.

[Granulosa cell tumors: structural and ultrastructural analysis]. / Tumores de células de la granulosa: análisis estructural y ultraestructural.

UNLABELLED: These ovarian neoplasm derive from the ovarian stromal component constituting around the 5 to 12% of all ovarian tumors. OBJECTIVE: To examine the histopathological and ultrastructural morphologic characteristic of the neoplastic cells and the patognomonic element of these tumors: Call Exner's Bodies MATERIALS AND METHODS: The materials corresponded to 2 women of 52 and 55 years. The syntomatology was abdominal tumor that went in increase. The materials were fractioned for the histopathological conventional study and for ultrastructural analysis. For this last one, they were fixed in Karnovsky, refix in osmio and included in Araldita. RESULTS: By means of the different observations it was determined in both cases the nuclear atipia, indentations nuclei and prominent nucleoli. In one of the cases the presence of Bodies of Call-Exner was detected, and ultrastructurally was compound by whirled fibrils and amorphous material, with dense structures electron to its around. It was interest the infiltrated of plasmatic cells around the tumors cells. These neoplasms are of interest due to their impredictible behavior and to the hormonal production that can originate alterations in other organs of the genital apparatus.

Tumores de células de la granulosa: analisis estructural y ultraestructural / Granulosa cell tumors: structural and ultrastructural analysis

Estas neoplasias ováricas derivan del componente estromal ovárico, constituyendo alrededor del 5 al 12 por ciento del total de los tumores ováricos. Objetivo: Examinar a nivel histopatológico y ultraestructural las características morfológicas de las células neoplásicas y del elemento patognomónico de estos tumores: los Cuerpos de Call Exner. Material y Métodos: Los materiales correspondieron a 2 mujeres de 52 y 55 años- La sintomatología era tumoración abdominal la cual iba en aumento. Los materiales fueron fraccionados para el estudio histopatológico convencional y para el análisis electromicroscópico. Para este último, fueron fijados en Fijador Karnovsky , refijados en osmio e incluídos en Araldita. Resultados: por medio de las diferentes observaciones se determinó en ambos casos la atipia nuclear, núcleos indentados y nucleólos prominentes.. En uno de los casos se detectó la presencia de Cuerpos de Call-Exner, que ultraestructuralmente estaban compuestos por fibrillas arremolinadas y material amorfo, con estructuras electrón densas a su alrededor. Fue llamativo el infiltrado de células plasmáticas alrededor de las células tumorales . Estas neoplasias son de interés debido a su conducta impredecible y a la producción hormonal que puede originar alteraciones en otros sistemas del aparato genital. (Au)

Ovarian small cell tumors: an electron microscopic review.

Small cell tumors of the ovary are uncommon but represent an important group to recognize in the differential diagnosis of primary and metastatic ovarian neoplasms. In some cases the correct diagnosis cannot be confidently made on the basis of clinical setting, routine light microscopy, and immunohistochemistry, and electron microscopy may be supportive or definitive in establishing cell type. The cell type is often important in choosing optimal therapy and in predicting prognosis. The authors performed electron microscopy on a moderate number of ovarian small cell tumors and here describe and illustrate the diagnostic features of representative examples of various types. The ultrastructural features of the metastatic tumors, such as embryonal rhabdomyosarcoma, neuroblastoma, and melanoma, are identical to those of their respective primary tumors, are well known, and usually pose no problem in diagnosis. On the other hand, the ultrastructural features of some primary ovarian small cell tumors may present a more difficult differential diagnosis, because they have features that are subtle and/or in common. Exemplary of tumors in this category are diffuse adult granulosa cell tumor, endometrial stromal sarcoma, and small cell carcinomas of the hypercalcemic and pulmonary (oat cell) types. Distinguishing among them may be difficult but is possible, and electron microscopy may be a valuable supplement to the diagnostic information obtained from the clinical presentation, light microscopy, immunohistochemistry and, in some tumors, cytometric analysis of these neoplasms.

Gynandroblastoma with elements resembling juvenile granulosa cell tumor.

Gynandroblastoma is an extremely rare sex cord-stromal tumor that exhibits significant ovarian and testicular differentiation. In most previously reported tumors, adult granulosa cell tumor has formed the ovarian-type component and Sertoli or Sertoli-Leydig cell tumor (SLCT) has formed the testicular-type component. In contrast, the ovarian-type element in the case reported here resembled juvenile granulosa cell tumor (JGCT). The testicular-type elements accounted for 20% of the tumor and resembled intermediate-grade SLCT. The Sertoli cells had strong cytoplasmic staining for cytokeratin CAM 5.2 and positive nuclear staining with estrogen and progesterone receptor, whereas the JGCT-like areas were negative for these antibodies. Ultrastructurally, the JGCT-like areas consisted of groups of cells that were invested by a basal lamina and had low nuclear-cytoplasmic ratios, cytoplasmic lipid droplets, and simple junctional complexes. The Sertoli cells in the SLCT-like areas had long, tight junctions and well-formed desmosomes. Gynandroblastoma usually presents clinically as an abdominal mass, often associated with either virilizing or feminizing manifestations. The prognosis is favorable and similar to that of the individual tumor components, but clinical follow-up in the small number of cases has been limited.

Adult-type granulosa cell tumor, presenting as extraovarian metastases: ultrastructural diagnosis.

All granulosa cell tumors have the potential to recur locally or metastasize, in spite of apparent complete surgical excision. Long-term follow-up is particularly important in these tumors, since recurrences may occur many years after the initial diagnosis. This report highlights the ultrastructural findings that led to the diagnosis of metastatic granulosa cell tumor in two patients presenting with extraovarian masses. In patient 1 the information about an ovarian granulosa cell tumor removed 9 years before the current admission was obtained only after the metastatic tumor was correctly diagnosed. In patient 2 the ovarian primary was found after abdominal wall involvement by granulosa cell tumor was diagnosed. Thus, in both cases the clinical circumstances were atypical and electron microscopic examination of the tumors was essential to make the diagnosis of granulosa cell tumor with confidence. Based on the features observed in these two extraovarian tumors as well as eight other primary ovarian granulosa cell tumors from our files, a consistent ultrastructural profile is identified that can be very useful for diagnosis.

Tumor de la célula granulosa juvenil del ovario / Young granulous cell tumor of the ovary

Los tumores derivados del estrome gonadal diferenciado corresponden aproximadamente al 5 por ciento de las neoplasias ováricas y dentro de éstos, los tumores de las células de la granulosa (TCG) son los más frecuentes. Existen dos variedades de TCG, siendo la variedad juvenil una entidad histopatológicamente diferente y la menos común. El propósito de éste trabajo es mostrar nuestra experiencia en tres casos de tumores de las células de la granulosa juvenil (TCGJ), tanto en los aspectos clínicos, terapéuticos, como asimismo en los hallazgos estructurales e inmunohistoquímicos encontrados

Smooth muscle differentiation in normal human ovaries, ovarian stromal hyperplasia and ovarian granulosa-stromal cells tumors.

An immunohistochemical and ultrastructural investigation on the presence of "smooth muscle differentiation" in stromal ovarian tissue was carried out in 10 adult granulosa cell tumors, six juvenile granulosa cell tumors, six thecoma/fibrothecomas, six cases of stromal hyperplasia, and in 10 normal ovaries. For immunohistochemistry, formalin-fixed paraffin-embedded tissues were processed using anti-alpha smooth muscle actin (alpha-SM actin) and anti-desmin as primary monoclonal antibodies. All adult granulosa cell tumors and juvenile granulosa cell tumors showed an intense alpha-SM actin immunoreaction, but weaker for desmin. Immunostain was diffuse in six out of 10 and five out of six adult granulosa cell tumors and juvenile granulosa cell tumors, respectively. Ultrastructurally, intermediate filaments focally converging into well developed desmosomes as well as peripheral bundles of myofilaments were documented both in adult granulosa cell tumors and juvenile granulosa cell tumors. In thecoma/fibrothecomas and stromal hyperplasia, alpha-SM actin and desmin expression was minimal or absent; on electron microscopy some "myoid" features and myofibroblasts were also seen. In normal ovaries, alpha-SM actin was found intensely expressed in the theca externa, focally identified in cortex-medulla, and unstained in the theca interna layer. Immunoreaction increased during folliculogenesis, going from a thin positive alpha-SM actin layer around secondary follicles to a strong diffuse stain in mature follicles. Our immunohistochemical and ultrastructural results indicate that a "smooth muscle differentiation" is a typical component of the specialized gonadal stromal tissue. A diffuse and focally alpha-SM actin is constantly present in granulosa cell tumors and thecoma/fibrothecomas, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Combined analysis of flow cytometry and morphometry of ovarian granulosa cell tumor.

BACKGROUND: It is difficult to determine the prognosis of granulosa cell tumors (GCT) at the time of diagnosis. METHODS: The nuclear DNA content of 17 patients with ovarian GCT was investigated by flow cytometry using paraffin-embedded tissue. Nuclear area (NA), nuclear perimeter (NP), and nuclear shape factor (NSF) were measured by an image analyzer using hematoxylin- and-eosin-stained sections. RESULTS: The follow-up period of the patients ranged from 2 months to 11 years. Thirteen tumors were diploid or near diploid, whereas one was tetraploid, and three were aneuploid. Two tumors had varying degrees of DNA content heterogeneity. Crude survival of the patients with an euploid tumor (13 diploid, 1 tetraploid) was more favorable than that of the patients with an aneuploid tumor. Patients with S-phase fraction (SPF) greater than 10% or DNA content heterogeneity experienced disease recurrence or metastasis. A significant difference was observed in NA and NP between those with and without metastasis. CONCLUSIONS: Our results indicate that DNA aneuploidy, large SPF, DNA content heterogeneity, and large NA and NP are adverse prognostic factors in GCT. Thus, flow cytometric and morphometric measurement may provide a rapid and valuable method to predict the biologic behavior of GCT.

Ovarian juvenile granulosa cell tumor associated with Maffucci's syndrome.

A 15-year-old girl developed a juvenile granulosa cell tumor associated with Maffucci's syndrome (enchondromatosis + hemangiomas). Clinical manifestations of the disease included an abdominal mass and progressive anemia. She underwent the removal of a Stage Ic juvenile granulosa cell tumor and subsequent adjuvant chemotherapy. On follow-up examination 4 years later, no recurrence of the ovarian tumor was noted. A review of the literature showed 10 previous cases of juvenile granulosa cell tumor associated with enchondromatosis, two associated with Maffucci's syndrome, and the rest with Ollier's disease (enchondromatosis). Ovarian juvenile granulosa cell tumor may occur not infrequently in female patients with enchondromatosis in the first or second decades, in contrast to the widely recognized sarcomatous changes of enchondromas that usually occur after the second decade. Data provided from these cases also emphasize the concept of a generalized mesodermal dysplasia.

Testicular granulosa cell tumor of the adult type.

A testicular granulosa cell tumor of the adult type was studied in a 61-year-old man with a history of diabetes and urinary bladder carcinoma. The tumor was composed of three areas, each with a distinctive histologic pattern: solid, cystic, and cordlike. Most of the tumor cells in the three patterns had a round to ovoid euchromatic nucleus with one or two large nucleoli and scanty cytoplasmic organelles, mainly mitochondria and rough endoplasmic reticulum. These cells showed slight immunopositivity for vimentin and no immunostaining for cytokeratins. Occasionally, elongated nuclei displaying membrane infoldings were observed. Pleomorphic nuclei were rare. The number of mitotic figures was low. Differential aspects of testicular and ovarian granulosa cell tumors are discussed.

[The morphogenetic potentials of endometrial and ovarian tumor cells when cultured on soft agar]. / Morfogeneticheskie potentsii kletok opukholei éndometriia i iaichnikov pri kul'tivirovanii v miagkom agare.

Morphofunctional peculiarities of tumor cells from 15 endometrial adenocarcinomas and 2 ovarian tumors have been investigated at the ultrastructural level. These cells could develop two types of colonies in soft agar: those with histotypical differentiation (numerous microvilli, well developed tight junctions, desmosomes, secretory granules), and those without it (absence of epithelial features, ability of tumor cells to produce filamentous extracellular matrix and striated collagen fibrils which are characteristic of fibroblastic cells). The addition of progesterone and tamoxifen to cell cultures resulted in rising the level of cell differentiation in the colonies. The fact that endometrial and ovarian cancer cells can express the properties specific of connective tissue cells may suggest a multipotention of the Mullerian epithelium derivatives to shed light on the histogenesis of the mixed Mullerian tumors of uterus.

[Tumor of the ovarian juvenile granulose cells. Presentation of a case with an immunohistochemical and ultrastructural study]. / Tumor de células de la granulosa juvenil del ovario. Presentación de un caso con estudio inmunohistoquímico y ultraestructural.

Female, 5 years old; first pregnancy of term, eutocic, weight 3,100 g; breast fed, complete vaccination program. A bronchial pathology that was present seven months later, yielded with medical treatment. Her illness started on September, 1984 after sever trauma by horse kick, presenting with a tumor in left illiac fossa; there was pain, improved by analgesics; the tumor continued to grow up to 5 x 6 cm in diameter, painful on palpation, causing hospital admission. Thirty days later an ultrasonographic study reported an ovoid echogenic and echolucid mass of 6.5 cm in left ovary; an infra-umbilical laparotomy was performed, finding a left ovarian tumarration, ovoid, pink white, with vascular areas, 24 x 18 x 15 cm at maximal diameters, solid, smooth and bright; at section there was gray-white, nodular tissue, with cystic cavities, 0.5 cm. Electronic microscopy an immunochemistry study were carried out in order to confirm the diagnosis of juvenile granulosa cell tumor. The patient died seven months later.