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 subepithelial

mesenchyme 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 penduculated

lesion

• 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