Smooth Muscle and Similar Lesions. Disclosure Statement. Smooth Muscle Tumors. Elizabeth Montgomery
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1 Smooth Muscle and Similar Lesions Elizabeth Montgomery Disclosure Statement Dr. Montgomery reports no relevant financial relationships with commercial interests. Smooth Muscle Tumors Most 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) 1
2 Gastric leiomyoma usually at gastroesophageal junction. Note: it is the same color as the muscularis mucosae and hypocellular Leiomyoma brightly eosinophilic cytoplasm and paranuclear vacuoles indenting the nucleus Uterine leiomyomas can extend into vessels 2
3 intravascular leiomyomatosis intravascular leiomyomatosis intravascular leiomyomatosis note the delicate longitudinal striations. These are usually hormone receptor+ 3
4 Intravascular leiomyomatosis desmin note the perfectly perpendicular fascicles Intravascular leiomyomatosis - actin Intravascular leiomyomatosis - ER 4
5 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 5
6 Benign metastasizing leiomyoma perpendicularly oriented brightly eosinophilic fascicles Benign metastasizing leiomyoma more delicate longitudinal striations, perpendicular fascicles Benign metastasizing leiomyoma - desmin 6
7 Benign metastasizing leiomyoma - keratin Lesion in retroperitoneum of a 40 year old woman (premenopausal) Myolipoma (lipoleiomyoma) 7
8 Myolipoma ER stain 8
9 GI Tract Leiomyomas Tend to arise in association with the lamina propria of the distal colon Can be found anywhere in the GI tract They are easy to diagnose and usually no immunolabeling is needed If you do a CD117/KIT stain, be aware of Cajal cell tendrils Colon leiomyoma associated with muscularis mucosae Rectal leiomyoma 9
10 Gastric leiomyoma Esopho-gastric junction leiomyoma Esopho-gastric junction leiomyoma KIT/CD117 stain pitfall alert intercalated Cajal cells 10
11 Leiomyoma of colon Colonic leiomyoma, smooth muscle actin immunostain Colon leiomyoma, KIT/CD117 stain 11
12 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 them Soft tissues>lungs>liver Most express actin, about half express desmin Am J Surg Pathol Jan;30(1): 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 AT 1, 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 12
13 Liver biopsy with Epstein Barr virusassociated smooth muscle neoplasm 13
14 Epstein Barr virusassociated smooth muscle neoplasm, in situ hybridization study Leiomyosarcoma Malignant smooth muscle neoplasms account for approximately 5-10% of all sarcomas. Most found in adults Female predominance They 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 14
15 Leiomyosarcoma perfect perpendicular orientation of fascicles Leiomyosarcoma. Blunt-ended nuclei and a paranuclear vacuole 15
16 A perfect paranuclear vacuole Paranuclear vacuole, leiomyosarcoma Leiomyosarcomas have NO characteristic translocation they are chromosome unstable note the anaphase bridge. Like benign lesions they also feature delicate cytoplasmic striations. No need to count mitoses. Any will do (except in uterus), where counts are important 16
17 Leiomyosarcoma, anaphase bridge Many retroperitoneal leiomyosarcomas arise in association with large blood vessels Retroperitoneal leiomyosarcoma associated with a large vein 17
18 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 18
19 Epithelioid leiomyosarcoma, gastrointestinal tract 19
20 Epithelioid leiomyosarcoma, GI tract, ER stain Epithelioid Leiomyosarcoma rare Pitfall - Epithelioid inflammatory myofibroblastic sarcoma (high grade form of inflammatory myofibroblastic tumor) -ALK rearrangements, responds to targeted therapy 20
21 Epithelioid inflammatory myofibroblastic sarcoma -ALK rearrangements, responds to targeted therapy. Note the neutrophils Epithelioid inflammatory myofibroblastic sarcoma -ALK rearrangements, responds to targeted therapy, note perinuclear pattern of ALK labeling Leiomyosarcoma versus Gastrointestinal Stromal Tumor (GISTs) Leiomyosarcomas are more pleomorphic Leiomyosarcomas have more blunt ended nuclei Leiomyosarcomas have pinker cytoplasm Leiomyosarcomas have perpendicularly oriented fascicles Leiomyosarcomas have abnormal mitoses GISTs can be more palisaded and have better paranuclear vacuoles 21
22 GIST Leiomyosarcoma GIST Leiomyosarcoma GIST Leiomyosarcoma 22
23 Exceptions with GISTs So called dedifferentiated GISTs after targeted treatment Some SDH deficient GISTs are pleomorphic SDH deficient GIST, plexiform pattern SDH deficient GIST 23
24 SDH deficient GIST SDH deficient GIST SDH deficient GIST, SDHB stain 24
25 Genital Stromal Tumors The all have the same immunolabeling pattern (variable ER, PR, desmin, actin, CD34) They are all benign All can contain fat You can waste a lot of time separating them The only one to separate is aggressive angiomyxoma, since it likes to recur but does not metastasize These are further discussed in another session Aggressive angiomyxoma Described by Steeper and Rosai (1983) Striking female predominance (6:1; F:M) Teens 70s. Mot in 30-40s Most vulvovaginal, pelvoperineal. Some in retroperitoneum, buttock, inguinal In scrotal and inguinal area in men, perianal Pain and pressure at presentation Recurrences 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 stroma containing fine strands of collagen and prominent variably-sized vessels 25
26 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 26
27 Aggressive angiomyxoma patchy desmin Aggressive angiomyxoma CD34 Aggressive angiomyxoma estrogen receptor 27
28 Angiomyofibroblastoma Angiomyofibroblastoma Usually arises in vulva; a few male cases reported Peak incidence 30-40s Usually small and well-marginated. Not likely to recur Same immunolabeling as all the other genital stromal tumors!!!!!! (often ER, PR, sometimes CD34, desmin, actin) Angiomyofibroblastoma, gross specimen - gelatinous 28
29 Angiomyofibroblastoma - Plump, epithelioid cells with a proclivity to concentrate around vessels in a nested and cord-like arrangement Angiomyofibroblastoma - Plump, epithelioid cells Some angiomyofibroblastomas have a fat component just like all the genital stromal types 29
30 Angiomyofibroblastoma fat and plump cells Cellular Angiofibroma Originally called angiomyofibroblastomalike 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 recur Well marginated, lobulated (not gelatinous) Cellular angiofibroma looks a bit like a spindle cell lipoma 30
31 Cellular angiofibroma - vessels with hyalinization, fibrinoid change no tumor cells cuffing them Cellular angiofibroma hyalinized vessels, ropy collagen Cellular angiofibroma, ER 31
32 Cellular angiofibroma with fat even fake lipoblasts Cellular angiofibroma overlapping cytology with angiomyofibroblastoma Cellular angiofibroma overlapping cytology with angiomyofibroblastoma BUT note the ropy collagen 32
33 Cellular angiofibroma the vessels are key Cellular angiofibroma This one is CD34- (different from spindle cell lipoma, solitary fibrous tumor) Cellular angiofibroma estrogen receptor 33
34 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 Fibroepithelial Stromal Polyp of The Lower Female Genital Tract coated by mucosa/skin Fibroepithelial stromal polyp; reactive stellate fibroblasts 34
35 Fibroepithelial stromal polyp; reactive stellate fibroblasts, sometimes multinucleated Superficial cervicovaginal myofibroblastoma Median age about 60 y; female patients Well marginated subepithelial lesions that involve the vagina, cervix, and vulva Most are small (largest reported 6 cm) Just under epithelium with a small Grenz zone Very bland can express desmin, actin, CD34. Often ER/PR+ 35
36 Myofibroblastoma Myofibroma Myopericytoma Myo Myo Myo Totally different but they sound alike so we mix them up!!!!! 36
37 Oh myo, myo, myo And we haven t even gotten to myoepithelioma Myofibroblastoma Noted 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 lobules Divergent immunohistochemical phenotype; express both CD-34 and desmin Myofibroblastoma looks like the one we saw in the cervicovaginal area!!!! 37
38 Myofibroblastoma bland cells, some collagen, scattered mast cells Myofibroblastoma CD34 Myofibroblastoma Desmin this makes it different from solitary fibrous tumor and spindle cell lipoma 38
39 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 May;13(5): 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 May;13(5): What the heck is an amianthoid fiber? am i an thoid (am-i- an 'thoyd), Having a crystalline appearance like that of asbestos. Synonym(s): asbestoid [G. amianthus, asbestos] Palisaded myofiboblastoma of lymph node Adult (median age about 50) Male predominance Primary in lymph nodes of inguinal region > various other sites Benign 39
40 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 Jul 14. [Epub ahead of print] PubMed PMID: Also express actin (but not usually desmin), cyclin D1 Palisaded myofiboblastoma of lymph node Palisaded myofibroblastoma of lymph node the famous fibers 40
41 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 41
42 Solitary Fibrous Tumor: Well-circumscribed fibrotic mass involving the bladder SFT: Alternating cellularity, patternless pattern, vessels Hypercellular Hypocellular Hypercellular Hypocellular Hypercellular 42
43 SFT: Alternating cellularity, patternless pattern, vessels Fat-forming (lipomatous) SFT Fat-forming (lipomatous) SFT: spindle cells intermixed with mature fat 43
44 Giant cell-rich SFT (Giant cell angiofibroma) Giant cell-rich SFT (Giant cell angiofibroma) Giant cell-rich SFT (Giant cell angiofibroma) 44
45 SFT: Frank malignant transformation Hypercellular Hypocellular Sarcomatous SFT: Frank malignant transformation CD34 Needle biopsy of fat-rich solitary fibrous tumor 45
46 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 Apr;38(4): PubMed PMID:
47 Another new cutie STAT6 SFTs harbor an NAB2-STAT6 fusion gene All SFT in study stained perfectly! Though some were heterogeneous 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 Apr;38(4): Small laparoscopic biopsy, has an odd pattern 47
48 BCL2 (a CD34 was similarly strongly reactive) STAT6 very reassuring for diagnosing solitary fibrous tumor. Strong nuclear labeling is seen 48
49 Thank you 49
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