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Smooth Muscle and Similar Lesions

Elizabeth Montgomery

Disclosure Statement

Dr. Montgomery reports no relevant financial relationships with commercial interests.

Smooth Muscle TumorsMost are leiomyomas (of the uterus usually) but they can be found in skin, gastrointestinal tract, rarely in retroperitoneum (often extra-uterine in females)Of course in body cavities, the differential diagnosis is always with gastrointestinal stromal tumor – easily resolved with modern immunolabeling (CD117, DOG1)

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Gastric leiomyoma – usually at gastroesophageal junction. Note: it is the same color as the muscularismucosae and hypocellular

Leiomyoma – brightly eosinophilic cytoplasm and paranuclear vacuoles indenting the nucleus

Uterine leiomyomas can extend into vessels –

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intravascular leiomyomatosis

intravascular leiomyomatosis

intravascular leiomyomatosis – note the delicate longitudinal striations. These are usually hormone receptor+

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Intravascular leiomyomatosis – desmin– note the perfectly perpendicular fascicles

Intravascular leiomyomatosis - actin

Intravascular leiomyomatosis - ER

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Intravascular leiomyomatosis - PR

Benign metastasizing leiomyoma – see in patients with uterine leiomyomas – they extend into veins and spread to lungs. Patients overall do well. ER/PR positive

Benign metastasizing leiomyoma

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Benign metastasizing leiomyoma –perpendicularly oriented brightly eosinophilic fascicles

Benign metastasizing leiomyoma – more delicate longitudinal striations, perpendicular fascicles

Benign metastasizing leiomyoma - desmin

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Benign metastasizing leiomyoma - keratin

Lesion in retroperitoneum of a 40 year old woman (premenopausal)

Myolipoma(lipoleiomyoma)

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Myolipoma – ER stain

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GI Tract LeiomyomasTend to arise in association with the lamina propria of the distal colonCan be found anywhere in the GI tract They are easy to diagnose and usually no immunolabeling is neededIf you do a CD117/KIT stain, be aware of Cajal cell tendrils

Colon leiomyoma associated with muscularis mucosae

Rectal leiomyoma

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Gastric leiomyoma

Esopho-gastric junction leiomyoma

Esopho-gastric junction leiomyoma – KIT/CD117 stain – pitfall alert –intercalated Cajal cells

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Leiomyoma of colon

Colonic leiomyoma, smooth muscle actin immunostain

Colon leiomyoma, KIT/CD117 stain

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Epstein Barr Virus (EBV)-Associated Smooth Muscle Tumors

Not good to call them leiomyosarcomas or leiomyomas ( “tumor” is suggested)Found in immunosuppressed persons (renal transplantation > AIDS > steroid therapy) .Multicentric rather than metastatic?Most patients do not die from themSoft tissues>lungs>liverMost express actin, about half express desminAm J Surg Pathol. 2006 Jan;30(1):75-82. Epstein-Barr virus-associated smooth muscle tumors are distinctive mesenchymal tumors reflecting multiple infection events: a clinicopathologic and molecular analysis of 29 tumors from 19 patients. Deyrup AT1, Lee VK, Hill CE, Cheuk W, Toh HC, Kesavan S, Chan EW, Weiss SW

Epstein Barr virus-associated smooth muscle neoplasm –this one has rounded cells and spindle cells

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Liver biopsy with Epstein Barr virus-associated smooth muscle neoplasm

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Epstein Barr virus-associated smooth muscle neoplasm, in situ hybridization study

LeiomyosarcomaMalignant smooth muscle neoplasms account for approximately 5-10% of all sarcomas. Most found in adultsFemale predominanceThey retain the general characteristics of smooth muscle differentiation (brightly eosinophilic cytoplasm, paranuclear vacuoles, delicate lingitudinal cytoplasmic striations)

Skin – leiomyosarcomas restricted to dermis essentially never metastasize (some prefer the term “atypical smooth muscle tumor”). Subcutaneous ones can metastasize. Note the perpendicularly oriented fascicles and brightly eosinophilic tumor cells

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Leiomyosarcoma – perfect perpendicular orientation of fascicles

Leiomyosarcoma. Blunt-ended nuclei and a paranuclear vacuole

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A perfect paranuclearvacuole

Paranuclearvacuole, leiomyosarcoma

Leiomyosarcomashave NO characteristic translocation – they are chromosome unstable – note the anaphase bridge. Like benign lesions they also feature delicate cytoplasmicstriations. No need to count mitoses. Any will do (except in uterus), where counts are important

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Leiomyosarcoma, anaphase bridge

Many retroperitoneal leiomyosarcomas arise in association with large blood vessels

Retroperitoneal leiomyosarcoma associated with a large vein

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Variants - Inflammatory leiomyosarcoma – often actin -, desmin + - some of these may be epithelioid inflammatory myofibroblastic sarcomas

Inflammatory leiomyosarcoma – often actin -, desmin+. This is a desmin stain

Myxoid Leiomyosarcoma

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Epithelioid leiomyosarcoma, gastrointestinal tract

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Epithelioid leiomyosarcoma, GI tract, ER stain

Epithelioid Leiomyosarcoma – rare

Pitfall - Epithelioid inflammatory myofibroblasticsarcoma (high grade form of inflammatory myofibroblastictumor) -ALK rearrangements, responds to targeted therapy

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Epithelioid inflammatory myofibroblasticsarcoma -ALK rearrangements, responds to targeted therapy. Note the neutrophils

Epithelioid inflammatory myofibroblasticsarcoma -ALK rearrangements, responds to targeted therapy, note perinuclear pattern of ALK labeling

Leiomyosarcoma versus Gastrointestinal Stromal Tumor (GISTs)

Leiomyosarcomas are more pleomorphicLeiomyosarcomas have more blunt ended nucleiLeiomyosarcomas have pinker cytoplasmLeiomyosarcomas have perpendicularly oriented fasciclesLeiomyosarcomas have abnormal mitosesGISTs can be more palisaded and have better paranuclear vacuoles

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GIST Leiomyosarcoma

GIST Leiomyosarcoma

GIST Leiomyosarcoma

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Exceptions with GISTsSo called “dedifferentiated” GISTs after targeted treatmentSome SDH deficient GISTs are pleomorphic

SDH deficient GIST, plexiform pattern

SDH deficient GIST

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SDH deficient GIST

SDH deficient GIST

SDH deficient GIST, SDHB stain

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Genital Stromal TumorsThe all have the same immunolabeling pattern (variable ER, PR, desmin, actin, CD34)They are all benignAll can contain fatYou can waste a lot of time separating themThe only one to separate is aggressive angiomyxoma, since it likes to recur but does not metastasizeThese are further discussed in another session

Aggressive angiomyxomaDescribed by Steeper and Rosai (1983)Striking female predominance (6:1; F:M)Teens – 70s. Mot in 30-40sMost vulvovaginal, pelvoperineal. Some in retroperitoneum, buttock, inguinalIn scrotal and inguinal area in men, perianalPain and pressure at presentationRecurrences in a high percentage (36-72%)Most lesions> 5 cm, can be well-marginated

Aggressive angiomyxoma - low to moderate cellularity, haphazardly arranged, short spindled and stellate-shaped cells set in myxoid, edematous stromacontaining fine strands of collagen and prominent variably-sized vessels

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Aggressive angiomyxoma - Medium to large-sized vessels with clusters of smooth muscle cells “spinning off” from the main vessel

Aggressive angiomyxoma – cells “spinning off” main vessel

Aggressive angiomyxoma –very hypocellular

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Aggressive angiomyxoma –patchy desmin

Aggressive angiomyxoma – CD34

Aggressive angiomyxoma –estrogen receptor

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Angiomyofibroblastoma

AngiomyofibroblastomaUsually arises in vulva; a few male cases reportedPeak incidence – 30-40sUsually small and well-marginated. Not likely to recurSame immunolabeling as all the other genital stromal tumors!!!!!! (often ER, PR, sometimes CD34, desmin, actin)

Angiomyofibroblastoma, gross specimen -gelatinous

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Angiomyofibroblastoma - Plump, epithelioidcells with a proclivity to concentrate around vessels in a nested and cord-like arrangement

Angiomyofibroblastoma -Plump, epithelioid cells

Some angiomyofibroblastomashave a fat component – just like all the genital stromal types……

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Angiomyofibroblastoma –fat and plump cells

Cellular AngiofibromaOriginally called “angiomyofibroblastoma-like tumor of the male genital tract” but found in men and woman alike (M:F=1:1)In older patients than the others (50s)Vulva (median size 3 cm), inguinal/scrotal (median size 7 cm)Seldom recurWell marginated, lobulated (not gelatinous)

Cellular angiofibroma– looks a bit like a spindle cell lipoma

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Cellular angiofibroma - vessels with hyalinization, fibrinoid change – no tumor cells cuffing them

Cellular angiofibroma –hyalinized vessels, ropy collagen

Cellular angiofibroma, ER

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Cellular angiofibroma with fat – even fake lipoblasts

Cellular angiofibroma –overlapping cytology with angiomyofibroblastoma

Cellular angiofibroma –overlapping cytology with angiomyofibroblastoma BUT note the ropy collagen

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Cellular angiofibroma – the vessels are key

Cellular angiofibroma – This one is CD34- (different from spindle cell lipoma, solitary fibrous tumor)

Cellular angiofibroma –estrogen receptor

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Fibroepithelial Stromal Polyps of The Lower Female Genital Tract

Common – found in vagina>vulva>cervix. Frequent in pregnant women (up to 20%)Some are very cellular (add a myogenin to address rhabdomyosarcoma in this setting)Can be desmin+Analagous to skin tags

FibroepithelialStromal Polyp of The Lower Female Genital Tract – coated by mucosa/skin

Fibroepithelial stromal polyp; reactive stellate fibroblasts

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Fibroepithelial stromal polyp; reactive stellate fibroblasts, sometimes multinucleated

Superficial cervicovaginal myofibroblastoma

Median age about 60 y; female patientsWell marginated subepithelial lesions that involve the vagina, cervix, and vulvaMost are small (largest reported 6 cm)Just under epithelium with a small Grenz zone Very bland – can express desmin, actin, CD34. Often ER/PR+

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Myo Myo MyoMyofibroblastomaMyofibromaMyopericytoma

Totally different but they sound alike so we mix them up!!!!!

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Oh myo, myo, myo

…And we haven’t even gotten to myoepithelioma

MyofibroblastomaNoted here since this name is similar to “myofibroma” and thus these two entities may be confused. Sixteen breast lesions having ultrastructural characteristics of myofibroblasts was described in 1987 as “myofibroblastomas” although a number of isolated cases had been described prior to this series.Extramammary lesions have subsequently been reported in a variety of sites; the lymph nodes were the first highlighted. Differ from myofibromas by lacking the hemangiopericytoma-like areas between lobulesDivergent immunohistochemical phenotype; express both CD-34 and desmin

Myofibroblastoma – looks like the one we saw in the cervicovaginal area!!!!

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Myofibroblastoma – bland cells, some collagen, scattered mast cells

Myofibroblastoma – CD34

Myofibroblastoma – Desmin – this makes it different from solitary fibrous tumor and spindle cell lipoma

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Palisaded myofiboblastoma of lymph node

Reported in 1989:Weiss SW, Gnepp DR, Bratthauer GL. Palisaded myofibroblastoma. A benign mesenchymal tumor of lymph node. Am J Surg Pathol. 1989 May;13(5):341-6.

Suster S, Rosai J. Intranodal hemorrhagic spindle-cell tumor with "amianthoid" fibers. Report of six cases of a distinctive mesenchymal neoplasm of the inguinal region that simulates Kaposi's sarcoma. Am J Surg Pathol. 1989 May;13(5):347-57.

What the heck is an amianthoid fiber?

am·i·an·thoid (am-i- an 'thoyd), Having a crystalline appearance like that ofasbestos.Synonym(s): asbestoid[G. amianthus, asbestos]

Palisaded myofiboblastoma of lymph node

Adult (median age about 50)Male predominancePrimary in lymph nodes of inguinal region > various other sitesBenign

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Palisaded myofiboblastoma of lymph node

Now known to have CTNNB1 mutations so β-catenin immunolabeling can help diagnose!Laskin WB, Lasota JP, Fetsch JF, Felisiak-Golabek A, Wang ZF, Miettinen M. Intranodal Palisaded Myofibroblastoma: Another Mesenchymal Neoplasm With CTNNB1 (β-catenin Gene) Mutations: Clinicopathologic, Immunohistochemical, and Molecular Genetic Study of 18 Cases. Am J Surg Pathol. 2014 Jul 14. [Epub ahead of print] PubMed PMID: 25025452.

Also express actin (but not usually desmin), cyclin D1

Palisaded myofiboblastomaof lymph node

Palisaded myofibroblastoma of lymph node – the famous fibers

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Palisaded myofibroblastoma of lymph node – the famous palisading!

Solitary Fibrous Tumor- The tumor formerly known as

hemangiopericytoma (among others)- May arise at any site in the body- Alternating hyper- and hypocellular regions,

“patternless pattern”, HPC vessels - CD34(+), CD99(+), BCL2(+), beta-cat (+/-)- Malignant criteria: frankly sarcomatous, >4

mits/10hpf, necrosis, packed cellularity- However, benign appearing lesions may met- Variants: fat-forming, giant cell-rich

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Solitary Fibrous Tumor: Well-circumscribed fibrotic mass involving the bladder

SFT: Alternating cellularity, patternless pattern, vessels

Hypercellular

Hypocellular

Hypocellular

Hypercellular

Hypercellular

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SFT: Alternating cellularity, patternless pattern, vessels

Fat-forming (lipomatous) SFT

Fat-forming (lipomatous) SFT: spindle cells intermixed with mature fat

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Giant cell-rich SFT (Giant cell angiofibroma)

Giant cell-rich SFT (Giant cell angiofibroma)

Giant cell-rich SFT (Giant cell angiofibroma)

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SFT: Frank malignant transformation

Hypercellular

Hypocellular

Sarcomatous

SFT: Frank malignant transformation

CD34

Needle biopsy of fat-rich solitary fibrous tumor

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Fat-rich solitary fibrous tumor -Wiry collagen, fat, “disorganized” pattern of cells

Fat-rich solitary fibrous tumor - CD34

Fat-rich solitary fibrous tumor – STAT6 nuclear labeling - Yoshida A, Tsuta K, Ohno M, Yoshida M, Narita Y, Kawai A, Asamura H, Kushima R. STAT6 immunohistochemistry is helpful in the diagnosis of solitary fibrous tumors. Am J Surg Pathol. 2014 Apr;38(4):552-9. PubMed PMID: 24625420.

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Another new cutieSTAT6SFTs harbor an NAB2-STAT6 fusion geneAll SFT in study stained perfectly! Though some were heterogeneousYoshida A, Tsuta K, Ohno M, Yoshida M, Narita Y, Kawai A, Asamura H, Kushima R. STAT6 immunohistochemistry is helpful in the diagnosis of solitary fibrous tumors. Am J SurgPathol. 2014 Apr;38(4):552-9.

Small laparoscopic

biopsy, has an odd pattern

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BCL2 (a CD34 was similarly

strongly reactive)

STAT6 – very reassuring for diagnosing solitary fibrous tumor. Strong nuclear

labeling is seen

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Thank you