Ovary
Sex cord stromal tumors
Fibroma
Author: Kyle C. Strickland, M.D., Ph.D.
Editorial Board Member: Carlos Parra-Herran, M.D.
Deputy Editor-in-Chief: Debra Zynger, M.D.
Topic Completed: 1 February 2018
Minor changes: 9 March 2020
Copyright: 2002-2020, PathologyOutlines.com, Inc.
PubMed Search: Fibroma[TI] ovary[TIAB]
See Also: Cellular fibroma
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Laboratory | Radiology description | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Electron microscopy description | Molecular / cytogenetics description | Differential diagnosis | Board review style question #1 | Board review answer #1Cite this page: Strickland KC. Fibroma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/ovarytumorfibroma.html. Accessed August 7th, 2020.
Definition / general
- Benign fibroelastic tumor of the ovary that can be hypo or hypercellular
Essential features
- Fibromas are stromal tumors composed of spindled, oval or round cells that produce variable amounts of collagen
- Cellular fibromas are a subset with high cellularity resembling granulosa cell tumors
- Cellular fibromas with ≥ 4 mitoses per 10 HPF are now termed "mitotically active cellular fibromas" and should be distinguished from fibrosarcoma
- It is important to differentiate benign fibroma from diffuse adult type granulosa cell tumor, a potential mimic
Terminology
- Fibroma
- Cellular fibroma: see Essential features
- Mitotically active cellular fibroma: see Essential features
- Fibroma with sex cord elements: see Microscopic description
ICD coding
Epidemiology
- Accounts for ~4% of ovarian tumors (Cancer 1981;47:2663)
- Most common sex cord stromal tumor, encompassing ~70% of this category
- Cellular fibromas represent ~10% of all fibromas
- Occur in patients 20 - 80 years, with an average age of ~50
- Often discovered incidentally
- Conventional fibromas are bilateral in 5 - 10% of cases, whereas cellular fibromas are invariably unilateral
Sites
- Ovary
Pathophysiology
- Meigs syndrome is defined as the presence of an adnexal mass accompanied by ascites and hydrothorax (Am J Obstet Gynecol 1937;33:249, Eur J Obstet Gynecol Reprod Biol 2000;92:199), which occurs in ~1% of patients with ovarian fibroma (Nucci: Gynecologic Pathology, 1st Edition, 2009)
- Gorlin syndrome (basal cell nevus syndrome) is an autosomal dominant disease characterized by multiple basal cell carcinomas of the skin, as well as odontogenic keratocysts, palmoplantar pits, ectopic calcifications and other abnormalities
- 2 - 25% of female patients with Gorlin syndrome are found to have ovarian fibromas, which are often bilateral, multinodular and calcified, particularly suspicious in pediatric populations (J Pediatr Adolesc Gynecol 2011;24:e5)
- Occurs in patients with mutations of the human homologue of the Drosophila gene PTCH (patched)
Etiology
- Arise from specialized fibroblasts of the ovarian stroma
Clinical features
- Most common clinical symptoms are abdominal pain, distension and increased urinary frequency
- Can be associated with ovarian torsion
- Up to 30% of patients with large fibromas, cellular fibromas and fibrosarcomas have ascites
Diagnosis
- Diagnosis of ovarian fibroma can be tentatively made grossly (see Gross description) and can often be made at frozen section evaluation
- Benign lesion characterized by a benign fibroblastic proliferation in the ovary and often adjacent to or continuous with ovarian stroma
Laboratory
- Can lead to increased serum CA125 (Gynecol Oncol 1995;59:405)
Radiology description
- Important radiologically because appears as a solid mass, mimicking malignancy (Radiographics 2002;22:1305)
- Ultrasonography typically reveals a large, solid pelvic mass separate from the uterus that appears homogeneous and hypoechoic with posterior acoustic shadowing (AJR Am J Roentgenol 1985;144:1239)
- CT imaging demonstrates a homogeneous solid tumor with delayed enhancement (Radiographics 2002;22:1305)
- On MRI, fibromas exhibit a low signal intensity on T1 weighted images and a remarkably low signal intensity (similar to skeletal muscle) on T2 weighted images (J Magn Reson Imaging 1997;7:465)
Prognostic factors
- In general, fibromas do not recur and are adequately treated by surgical excision
- Ovarian surface involvement or adhesions are seen in 6% of cellular fibromas and 10% of mitotically active cellular fibromas
- Likewise, 11% of patients with cellular fibromas and 13% of those with mitotically active fibromas are found to have extraovarian spread at surgery; however, these patients have a benign clinical follow up (Am J Surg Pathol 2006;30:929)
- Cellular fibromas have been reported to recur (Cancer 1981;47:2663); thus, long term follow up is recommended
Case reports
- 40 year old woman with a rare case of bilateral ovarian fibroma presenting as Meigs syndrome (J Obstet Gynaecol 2013;33:636)
- 65 year old woman with recurrence of mitotically active cellular fibroma of the ovary (Obstet Gynecol Int 2009;2009:803062)
- 66 year old woman with extraovarian fibroma with minor sex cord elements (Int J Surg Pathol 2017;25:472)
- 73 year old woman with cellular fibroma of the ovary with Meigs syndrome and elevated CA125 (J Reprod Med 1995;40:817)
Treatment
- Fibromas are adequately treated by surgical excision
- Cellular fibromas require long term follow up, particularly in the setting of ovarian surface involvement, intraoperative rupture or extraovarian spread
Gross description
- Nearly all are firm and have a smooth lobulated surface
- Up to 20% present as pedunculated or polypoid growths on the surface of the ovary (Nucci: Gynecologic Pathology, 1st Edition, 2009)
- Size range from 1 - 21.5 cm (average 6 cm) (Nucci: Gynecologic Pathology, 1st Edition, 2009)
- Cut surface of conventional fibroma has a solid white or tan / yellow appearance
- About 1/4 of all fibromas have cystic changes and about 1/3 of cellular fibromas contain cysts; edema is frequent
- Calcifications are seen in up to 10% (Nucci: Gynecologic Pathology, 1st Edition, 2009)
- If associated with ovarian torsion, fibromas will often exhibit hemorrhage and necrosis
- Cut surface of cellular fibromas may appear fleshy (Cancer 1981;47:2663)
- In contrast, fibrosarcomas are often large and have a soft cut surface, often containing areas of hemorrhage or necrosis
Gross images
AFIP images
Various images
Contributed by Rex Bentley, M.D.
Ovarian fibroma
Images hosted on other servers:
Fibroma
Fibrothecoma
Microscopic (histologic) description
- Composed of thin spindle cells in a whorled arrangement
- Nuclei are bland, wavy and fusiform and the cytoplasm is eosinophilic, blending with a variable amount of extracellular collagen
- Cytologic atypia is rare
- 10% are hypercellular, containing little intercellular collagen (Fletcher: Diagnostic Histopathology of Tumors, 4th Edition, 2013)
- Cellular fibromas are composed of small cells arranged in herringbone, cross stitched or storiform patterns
- Cells contain bland spindled nuclei and can exhibit up to 1 - 3 mitoses per 10 HPF (Cancer 1981;47:2663)
- In an otherwise typical cellular fibroma, the term "mitotically active cellular fibroma" (MACF) has been proposed for tumors that demonstrate > 4 mitoses per 10 HPF (Am J Surg Pathol 2006;30:929), which should be considered a tumor of uncertain malignant potential
- Occasionally, sex cord elements are present in fibromas, which do not have any prognostic significance if present in less than 10% of the tumor
- These tumors can be diagnosed as fibroma with sex cord elements
Microscopic (histologic) images
Contributed by Kyle C. Strickland, M.D., Ph.D.
Fibroma at low power
Fibroma with edematous change
Typical fibroma
Fibroma at high power
Light SF1 staining
CD99 negative
Contributed by Rex Bentley, M.D.
Fibroma with dense collagen
Cellular fibroma
Positive stains
- WT1, SF1 and FOXL2 stain nearly all fibromas, while inhibin and calretinin have variable expression (Am J Surg Pathol 2009;33:354, Am J Surg Pathol 2011;35:484)
- Vimentin is also positive in fibromas (J Pathol 1987;152:253)
- CD56, ER β and PR are reliably positive (> 95%) and SMA, S100 and CD34 can be occasionally positive (Am J Surg Pathol 2008;32:884)
- Inhibin and calretinin can be helpful when determining if sex cord elements are present but will also be positive in 50% and 25% of fibromas, respectively
- Reticulin is often used to distinguish diffuse adult type granulosa cell tumor (GCT) from fibroma
- Fibromas will exhibit an individual pericellular reticulin staining pattern, whereas GCT will exhibit a nested pattern of reticulin staining
Negative stains
- CD10 is negative (can help distinguish from endometrial stromal tumors) (Int J Gynecol Pathol 2007;26:359)
- Desmin and caldesmon are negative (can help distinguish fibroma from smooth muscle tumors involving the ovary)
- CD99 is negative (can help distinguish from adult granulosa cell tumors which is positive in up to 88% of cases) (Am J Surg Pathol 2009;33:354)
Electron microscopy description
- Ultrastructural examination of typical ovarian fibromas demonstrates numerous thin, elongated cells with intercommunicating cytoplasmic processes admixed with abundant collagen fibrils (Cancer 1971;27:438)
- Fibrils appear grouped in bundles with a crossbanding pattern composed of a light band bound by two thin dark bands (recurring at intervals of 600 Å)
- Cells appear to have indistinct cell borders and are compressed by collagenous stroma
- Little cytoplasm is present, which contains few mitochondria and scant endoplasmic reticulum
- Nuclei appear elongated and thin, with marked heterochromatin condensation noted at the periphery of the nucleus
- Ultrastructural examination of malignant ovarian fibroma reveals ovoid to spindle shaped nuclei with a moderate amount of cytoplasm and lipid vacuoles present intra and extracellularly (J Clin Pathol 1998;51:868)
- Poorly formed adhesions are present between adjacent cells and a discontinuous lamina is present at the cell surface
- Collagen fibrils can be seen in the interstitium
Molecular / cytogenetics description
- Trisomy 12 is a common cytogenetic abnormality associated with benign ovarian fibromas (Genes Chromosomes Cancer 1990;2:48, Gynecol Oncol 1990;38:28)
Differential diagnosis
- Diffuse adult granulosa cell tumor (GCT):
- Cells often demonstrate grooved nuclei at high magnification, in contrast to fibroma
- As mentioned above under Positive stains, reticulin staining is exceptionally useful to distinguish fibroma
- FOXL2 mutations are reported and do not occur in fibromas (Am J Surg Pathol 2011;35:484, N Engl J Med 2009;360:2719)
- Nested reticular staining correlates with positive FOXL2 mutations (Int J Gynecol Pathol 2018;37:305)
- Endometrial stromal tumor:
- CD10 positive, whereas fibromas are invariably CD10 negative
- Positive for JAZF1 / SUZ12 gene fusions by FISH but only present in 75% of endometrial stromal nodules and 50% of low grade endometrial stromal sarcomas, so a negative result may be inconclusive (Orphanet J Rare Dis 2016;11:15)
- Fibrosarcoma:
- Exceptionally rare
- Mitoses ≥ 4 mitoses per 10 HPF, hypercellularity, nuclear pleomorphism, older patients (mean age 58) and extraovarian extension / adhesions (Cancer 1981;47:2663)
- Presence of 4 or more mitotic figures is not enough to diagnose fibrosarcoma, as the differential includes mitotically active cellular fibroma (MACF) (Am J Surg Pathol 2006;30:929)
- Leiomyoma: will appear more fascicular histologically and typically be positive for desmin and caldesmon
- Ovarian stromal hyperplasia:
- Usually a bilateral process characterized by diffuse and cellular proliferation of stromal cells
- Although it may have a nodular appearance grossly, stromal hyperplasia should lack collagenous stroma and hyaline plaques
- Sex cord stromal tumor, NOS: if > 10% of the tumor contains sex cord elements, consider this diagnosis
- Thecoma / fibrothecoma:
- Fibromas and thecomas have histomorphologies that substantially overlap and the term "fibrothecoma" is often used to encapsulate tumors that exhibit features of both
- Thecomas are composed of tumor cells with abundant pale or vacuolated cytoplasm and typically stain positive for CD10 and inhibin, in contrast to fibromas
- Thecomas may also present with virilization (more common in luteinized thecoma) and may present with endometrial adenocarcinomas, secondary to increased estrogen production (Nucci: Gynecologic Pathology, 1st Edition, 2009)
Board review style question #1
You receive an intraoperative consultation from the surgical team for bilateral multinodular ovarian masses in a 16 year old patient. Biopsy of the lesion demonstrates bland, monomorphic spindled cells with a collagenous stroma. Mutation of which of the following is most likely associated with the patient's condition:
- FOXL2
- HMGA2
- JAZF1
- PTCH
- Vimentin
Board review answer #1
