Molecular assessment of testicular adult granulosa cell tumor demonstrates significant differences when compared to ovarian counterparts

The differential diagnosis for precocious puberty in a young female includes peripheral causes. This case report documents a rare cause of isosexual precocious puberty, a juvenile granulosa cell tumour of the ovary–and a brief literature review. A one year-old baby girl presented with mass abdomen, vaginal discharge and rapid onset of pubertal development. She underwent an exploratory laparotomy for tumour resection. Pathology reported a juvenile granulosa cell tumour of the ovary. Early stage granulosa cell tumor surgically treated has good prognosis. Adjuvant chemotherapy is not indicated in this setting.

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FOXO1 mitigates the SMAD3/FOXL2C134W transcriptomic effect in a model of human adult granulosa cell tumor

Journal of Translational Medicine ◽

10.1186/s12967-021-02754-0 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Christian Secchi ◽

Paola Benaglio ◽

Francesca Mulas ◽

Martina Belli ◽

Dwayne Stupack ◽

...

Keyword(s):

Granulosa Cell ◽

Chromatin Remodeling ◽

Granulosa Cell Tumor ◽

Cell Tumor ◽

Rna Seq ◽

Pathogenic Role ◽

Rare Type ◽

Cellular Models ◽

Genome Wide

Abstract Background Adult granulosa cell tumor (aGCT) is a rare type of stromal cell malignant cancer of the ovary characterized by elevated estrogen levels. aGCTs ubiquitously harbor a somatic mutation in FOXL2 gene, Cys134Trp (c.402C < G); however, the general molecular effect of this mutation and its putative pathogenic role in aGCT tumorigenesis is not completely understood. We previously studied the role of FOXL2C134W, its partner SMAD3 and its antagonist FOXO1 in cellular models of aGCT. Methods In this work, seeking more comprehensive profiling of FOXL2C134W transcriptomic effects, we performed an RNA-seq analysis comparing the effect of FOXL2WT/SMAD3 and FOXL2C134W/SMAD3 overexpression in an established human GC line (HGrC1), which is not luteinized, and bears normal alleles of FOXL2. Results Our data shows that FOXL2C134W/SMAD3 overexpression alters the expression of 717 genes. These genes include known and novel FOXL2 targets (TGFB2, SMARCA4, HSPG2, MKI67, NFKBIA) and are enriched for neoplastic pathways (Proteoglycans in Cancer, Chromatin remodeling, Apoptosis, Tissue Morphogenesis, Tyrosine Kinase Receptors). We additionally expressed the FOXL2 antagonistic Forkhead protein, FOXO1. Surprisingly, overexpression of FOXO1 mitigated 40% of the altered genome-wide effects specifically related to FOXL2C134W, suggesting it can be a new target for aGCT treatment. Conclusions Our transcriptomic data provide novel insights into potential genes (FOXO1 regulated) that could be used as biomarkers of efficacy in aGCT patients.

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Adult‐type granulosa cell tumor of the ovary: a FOXL2 ‐centric disease

The Journal of Pathology Clinical Research ◽

10.1002/cjp2.198 ◽

2021 ◽

Author(s):

Jessica A Pilsworth ◽

Dawn R Cochrane ◽

Samantha J Neilson ◽

Bahar H Moussavi ◽

Daniel Lai ◽

...

Keyword(s):

Granulosa Cell ◽

Granulosa Cell Tumor ◽

Cell Tumor ◽

Adult Type

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Multiple recurrence of granulosa cell tumor of the ovary: A case report and literature review

10.1055/s-0039-1685319 ◽

2016 ◽

Author(s):

Varkha Chandra ◽

Sandhya Jain ◽

Neerja Goel ◽

Bindia Gupta ◽

Shalini Rajaram

Keyword(s):

Case Report ◽

Granulosa Cell ◽

Adnexal Mass ◽

Malignant Tumors ◽

Abdominal Mass ◽

Pelvic Mass ◽

Granulosa Cell Tumor ◽

Cell Tumor ◽

Surgical Staging ◽

Granulosa Cell Tumors

Introduction: Granulosa cell tumors comprise approximately 5% of all ovarian malignancy and account for 70% of malignant sex cord stromal tumors. Granulosa cell tumors have been diagnosed from infancy, the peak incidence being perimenopausal age. The potential of malignancy of these tumors is low, recurrences are often late and found in 10-33% of cases. Case Report: A 32-year-old P1L1 presented with large abdominal mass for which she underwent staging laparotomy with debulking surgery. She was a known case of granulosa cell tumor in the past and had undergone three laparotomies, along with chemotherapy. At the age of 13 yrs, she was diagnosed with a stage IA granulosa cell tumor (GCT) of the ovary first time. She underwent surgical staging and removal of left sided adnexal mass, after which she was asymptomatic for 7 years. In 2003 she again presented with lump abdomen for which she underwent resection of adnexal mass, histopathology was consistent with recurrent GCT. After second surgery she also received two cycles of chemotherapy. Despite adjuvant chemotherapy, patient presented again after three years in 2006 with adnexal mass and was found to have a third recurrence. At that time, she received 6 cycles of chemotherapy and the mass regressed. Meanwhile she got married and had one child. After four year in 2010 she again presented with lump abdomen and she underwent surgical staging, total abdominal hysterectomy with right salphingo ophorectomy along with removal of mass. After five year in 2015 she again presented with lump abdomen; there was a large pelvic mass which was removed and patient referred for chemotherapy. Discussion: GCTS which a rare malignant tumors of ovary tend to be associated with late recurrences. Although most recurrences occurs within 10 years after initial diagnosis, there are occasional reports of recurrences after10 years. We experienced the rare case of a patient who relapsed multiple times over 20 years, despite surgical and targeted treatment. Conclusion: The long history of granulosa cell tumor highlights the importance of extended follow up of the patient.

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