An Overview of Genital Stromal Tumors
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1 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
2 Financial disclosures Book Royalties
3 General 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
4 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
5 Fibroepithelial Stromal Polyp 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
6 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
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12 Immunohistochemistry Consistently reactive for Desmin Estrogen Receptor (ER) Progesetrone Receptor (PR) Sometimes Smooth Muscle Actin
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15 Enbryonal Rhabdomyosarcoma Rhabdomyoma
16 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
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20 Immunohistochemistry Desmin in % of cases ER/PR in % CD34 in 50-85% SMA in 0-45%
21 Synonym Cellular Angiofibroma 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
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29 Immunohistochemistry Inconsistent expression Variable expression of CD34, desmin, SMA P16 positivity in sarcomatous areas p16
30 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)
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35 Immunohistochemistry Frequently positive for CD34 and Desmin (~90%) CD34 Desmin Rare cases negative for both (~3%)
36 Prognosis Benign tumor Local excision curative No evidence of significant recurrence risk even in the presence of positive resection margins
37 RB1 and Genital Stromal Tumors
38 Mammary-type myofibroblastoma RB1 Cellular Angiofibroma RB1
39 Angiomyofibroblastoma Benign mesenchymal neoplasm of the vulva and vagina Uncommonly may present as a penduculated lesion Most grossly well-circumscribed and smaller than 5cm
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43 Immunohistochemistry Positive for Desmin, ER & PR Less commonly CD34 and SMA positivity Desmin
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45 Deep Angiomyxoma 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 4 th decade of life with painless cystic mass often exceeding 10cm
46 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
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49 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
50 Reactive changes Smooth Muscle Tumor WDL Superficial Angiomyxoma
51 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
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54 Prepubertal Vulval Fibroma
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56 Myxoid Collagenous
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62 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
63 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
64 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
65 LEIOMYOMA Epithelioid morphology Myxoid changes
66 LEIOMYOSARCOMA Some combination of cytologic atypia, increased mitotic activity Increased size infiltrative growth
67 Smooth Muscle Tumors of the Vulva Leiomyomas of the vulva is one of the more common vulvar mesenchymal neoplasms Present in 4 th to 5 th 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
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71 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
72 Differential Diagnosis 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
73 KonstantinosLin
Notice of Faculty Disclosure
Mesenchymal Tumors of the Vulva: Old, New, Something(s) Different Napa Valley Conference Pathology Education Partners Inc May 15, 2018 Teri A. Longacre, M.D. longacre@stanford.edu Stanford University,
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