20 September 2007 Case of the Week #96
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We thank Dr. Jamie Shutter, University of South Florida, Tampa, Florida (USA), for contributing this case. This case was reviewed in May 2020 by Dr. Jennifer Bennett, University of Chicago and Dr. Carlos Parra-Herran, University of Toronto.
Case of the Week #96
Clinical History
The patient was a 55 year woman with a 24 cm pelvic mass, massive ascites and a diffusely nodular omentum. The mass was excised.
Gross images: image #1
Micro images: low/medium power - image #2; #3; #4; #5
high power - image #6
What is your diagnosis?
Diagnosis:
Granulosa cell tumor - adult type
Discussion
This is a relatively straight forward case of a common tumor in women. Most (75%) cases are associated with hyperestrogenism. In children, these tumors may cause precocious puberty, and in adults, they may be associated with metrorrhagia or endometrial hyperplasia / carcinoma.
The tumor grossly is an encapsulated cystic or solid tumor with straw colored or mucoid fluid. Microscopically there are small, bland, cuboidal to polygonal cells in various patterns, including Call-Exner bodies (small follicle-like structures containing eosinophilic material), macrofollicular, trabecular, solid or insular (island-like) patterns. Focal luteinization (plump cells with abundant cytoplasm) may be present, particularly during pregnancy. The tumor cells often have distinctive coffee bean shaped nuclei (also called folded nuclei or nuclear grooves).
These tumors have a good prognosis, with a 10 year survival over 90%. However, they may recur late, even after 20 years, and 5-25% may have malignant behavior, which cannot be predicted from morphology. In the present case, the omental nodules were only reactive mesothelial hyperplasia, and not metastases.
Adult granulosa cell tumors are usually immunoreactive for inhibin (image #7), calretinin (AJSP 2002;26:1477), vimentin and smooth muscle actin. However, reliance of immunostains for diagnosis is dangerous, as these tumors may also be immunoreactive for CD99 (Mod Path 1998;11:769), S100 (50%) and keratin. This is a particular problem for tumors resembling poorly differentiated surface epithelial carcinoma (Virchows Arch A Pathol Anat Histopathol 1989;414:439), which is also keratin positive, although with diffuse staining, in contrast to the dot-like keratin staining of granulosa cell tumors (AJSP 1992;16:962). The differential diagnosis of granulosa cell tumors also includes endometrial stromal sarcoma, endometrioid carcinoma, small cell carcinoma of hypercalcemic type, and pregnancy related granulosa cell proliferation (Hum Path 1988;19:657)
Distinctive nuclear grooves are not specific to granulosa cell tumors, as indicated in the table below. The table would be even larger if it included entities with nuclear folds, slight nuclear grooving, tumor cells with nuclear irregularities or grooves in cytologic specimens (Acta Cytol 2001;45:48).
Cells or diseases with distinctive nuclear grooves (partial list)
Normal or reactive
Lymphoblasts and lymphocytes (centrocytes)
Histiocytes (normal and inflammatory conditions)
Osteoblasts
Granulosa cells, Sertoli cells
Melanocytes, sebaceous glands, Langerhans cells
Prostate basal cells (some)
Mesothelial hyperplasia
Urothelial metaplasia
Hematopoietic malignancies
Leukemia: AML-M3, M4, M5
Lymphoblastic leukemia/lymphoma
Granulocytic sarcoma
Hairy cell leukemia
Histiocytic sarcoma
Diffuse large B cell lymphoma (occasionally)
Mantle cell lymphoma-blastoid variant
Bone and Soft tissue tumors
Liposarcoma-myxoid/round cell
Giant cell tumor of tendon sheath
Adamantinoma
Chondroblastoma
Desmoplastic small round cell tumor
Epithelioid hemangioendothelioma
Epithelioid angiosarcoma
Papillary tumors
Papillary thyroid carcinoma
Papillary tumor of pineal region
Solid pseudopapillary neoplasm of the pancreas
Other papillary tumors
Gynecologic
Granulosa cell tumor
Sex cord tumor with annular tubules
Brenner tumor
Fallopian tube Walthard cell nests
Cervix - normal cells, ASCUS, dysplasia
Other
Hyalinizing trabecular adenoma of thyroid gland
Pleomorphic adenoma of salivary gland
Langerhans cell histiocytosis
Breast myofibroblastoma
Clear cell sarcoma of kidney
Epithelioid GI stromal tumor
Ependymoma
Melanocytoma of CNS
Nuclear grooves and other nuclear envelope irregularities may be physiologic (normal cells) or due to altered expression of cytoplasmic intermediate filaments, actin or tubulin (tumor cells). For example, disruption of vimentin intermediate filaments causes nuclear folds or invaginations in cell lines (J Cell Sci 1994;107:1593). The RET/PTC oncogene, associated with papillary thyroid carcinoma, can rapidly induce nuclear envelope irregularities, perhaps by generating external forces on the nuclear envelope via intermediate filaments (Am J Pathol 2003;163:1091).
The function of nuclear grooves is not understood. In plants, they provide an increased nuclear surface area that may promote transport across the nuclear membrane (Plant Cell 2000;12: 2425). Whether this occurs in humans is unknown.
Additional references: PathologyOutlines.com - Ovary chapter
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