An Overview of Genital Stromal Tumors

By Konstantinos Linos MD, FCAP, FASDP

Bone, Soft Tissue and Dermatopathology

Assistant Professor of Pathology

Dartmouth-Hitchcock Medical Center

Geisel School of Medicine at Dartmouth

Hanover, NH, USA

• Book Royalties

Financial disclosures

• Broad variety of soft tissue tumors exclusively in vulvovaginal and inguinoscrotal sites

• Probably originate from a distinct zone of subepithelial stromal cells or subepithelialmesenchyme extending from the endocervix

• Striking morphologic, immunophenotypic and genetic overlap

General

• Fibroepithelial Polyp• Superficial Myofibroblastoma• Cellular angiofibroma• Mammary-type myofibroblastoma• Angiomyofibroblastoma• Deep/”Aggressive” angiomyxoma• Superficial Angiomyxoma• Prepubertal Vulvar Fibroma• Lipoblastoma-Like tumor of the vulva• Smooth Muscle Tumors of the external

genitalia

• Synonyms• Mesodermal stromal polyp• Cellular Pseudosarcomatous fibroepithelial

stromal polyp• Pseudosarcoma botryoides

• Benign polypoid growth of the vagina, vulva or cervix

• Strongly tied to hormonal stimulation

Fibroepithelial Stromal Polyp

• Most often during pregnancy • also in reproductive age women• Postmenopausal women undergoing hormonal

replacement

• Regression in the postpartum period is typical

• Typical clinical presentation is one or more polyps that may be symptomatic

• Usually 1-5cm

Immunohistochemistry

• Consistently reactive for• Desmin• Estrogen Receptor (ER)• Progesetrone Receptor (PR)• Sometimes Smooth Muscle Actin

Enbryonal

Rhabdo-

myosarcoma

Rhabdomyoma

Superficial (cervicovaginal) myofibroblastoma

• Benign tumor that may arise in the vulva, vagina or cervix

• Nodular or polypoid painless mass in adults most commonly in their 50s

• Grossly well-circumscribed, firm and dense mass from 1 to 6.5cm

Immunohistochemistry• Desmin in 75-100% of cases

• ER/PR in 80-100%

• CD34 in 50-85%

• SMA in 0-45%

Cellular Angiofibroma• Synonym

• Angiomyofibroblastoma-like tumor of the male genital tract

• Benign neoplasm in vulvovaginal and inguinoscrotal areas

• Middle-aged patients with a female predominance

• Classically subcutaneous painless nodule usually not exceeding 7cm

Immunohistochemistry

• Inconsistent expression

• Variable expression of CD34, desmin, SMA

• P16 positivity in sarcomatous areas

p16

Mammary-type Myofibroblastoma

• Initially described in breast • Can arise anywhere in soft tissue • Predilection for inguinal and pelvic region

• Most cases occur in men

• Median age 53

• Range 1-22cm (median size of 6cm)

Immunohistochemistry

• Frequently positive for CD34 and Desmin (~90%)

• Rare cases negative for both (~3%)

CD34 Desmin

• Benign tumor

• Local excision curative

• No evidence of significant recurrence risk even in the presence of positive resection margins

Prognosis

RB1 and Genital Stromal Tumors

Mammary-type

myofibroblastoma

Cellular

Angiofibroma

RB1

RB1

• Benign mesenchymal neoplasm of the vulva and vagina

• Uncommonly may present as a penduculatedlesion

• Most grossly well-circumscribed and smaller than 5cm

Angiomyofibroblastoma

Immunohistochemistry • Positive for

Desmin, ER & PR

• Less commonly CD34 and SMA positivity

Desmin

• Synonym: “Aggressive” angiomyxoma• Low Grade, locally infiltrative myxomatous

neoplasm specific to the deep vulvovaginal, perineal and pelvic tissues

• Strong female predisposition • In men in the analogous inguinoscrotal and

perineal regions • Usually 4th decade of life with painless cystic

mass often exceeding 10cm

Deep Angiomyxoma

• Less aggressive course than initially described if completely excised with negative margins

• Potential for local destructive recurrence some times years (often decades) after initial excision• Even tumors as small as 3cm have recurred

multiple times• Grossly soft gelatinous tumor with ill-defined

margins • In recurrent cases may have more fibrous

appearance

Immunohistochemistry• Typically positive for:

• Desmin• SMA• ER/PR• Variable CD34 positivity

• Structural rearrangements of the region 12q15• ~30% of tumors, intragenic/extragenic

• HMGA2 and CDK4 IHCs positive• When positive, useful in confirming the diagnosis

and assessing margins status in a subset of cases

Reactive changes Smooth Muscle Tumor

WDL Superficial Angiomyxoma

Superficial Angiomyxoma• Can also occur in the genital region of women • Include this entity in the differential of

myxoid lesions of the distal female genital tract

• Association with Carney complex less clear with lesions in the genital area

• Typically polypoid and usually less than 5cm• Potential for local nondestructive recurrence in

~30-40% of cases

Prepubertal Vulval Fibroma

Myxoid Collagenous

Loss of RB1 by IHC

• Lack of PLAG1 and HMGA2

expression suggests it is

distinct from “true”

lipoblastomas

• Loss of Rb1 suggests possible

role of 13q chromosomal

alterations

• Possible relationship with the

Spindle cell lipoma family

Practical approach

• Correct Identification of Aggressive Angiomyxoma is critical

• If above has been excluded and definitive classification is not possible you can use label• “Benign Genital Stromal Tumor”

Smooth Muscle Tumors of the External Genitalia

• Smooth muscle tumors of vulva, vagina, and scrotum have similar gross and pathologic features to soft tissue and uterine counterparts

• Criteria for malignancy depend on the specific site

• Soft tissue• Superficial (including nipple)• Genital • Deep seated

Epithelioid morphology

Myxoid changes

LEIOMYOMA

LEIOMYOSARCOMA

Some combination of

• cytologic atypia,

• increased mitotic

activity

• Increased size

• infiltrative growth

Smooth Muscle Tumors of the Vulva

• Leiomyomas of the vulva is one of the more common vulvar mesenchymal neoplasms • Present in 4th to 5th decade as a small (<3cm)

mass• Mutliple leiomyomas may be manifestation of

Alport Syndrome• Hereditary disorder

• Glomerulonephritis, ocular abnormalities & hearing loss

• Mutation in COL4A3, COL4A4, COL4A5

Smooth Muscle Tumors of the Scrotum

• Uncommon and most are leiomyosarcomas• Cytologic atypia, mitotic activity and necrosis

• Rare in this location tumors with absence of atypia or mitotic activity• Extensive sample is necessary before apply the

diagnosis of leiomyoma • Note long-term clinical follow-up

• Any mitotic activity warrants classification as malignant

• Neurofibroma• S100-protein/SOX 10 +

• Solitary Fibrous Tumor• STAT6 positive

• Inflammatory Myofibroblastic Tumor• ALK + in 50-60% of cases

• Sarcomatoid Carcinoma• Diffuse cytokeratin expression• Examine for High Grade Squamous Intraepithelial

lesion or dVIN

Differential Diagnosis

• Email: Konstantinos.Linos@hitchcock.org

• @ @ KonstantinosLin