Disclosures I have nothing to disclose. Pleomorphic sarcomas: MFH, - - PowerPoint PPT Presentation
Disclosures I have nothing to disclose. Pleomorphic sarcomas: MFH, where did you go? Andrew Horvai, MD, PhD Clinical Professor, Pathology 78 year old man Questions Where did the diagnosis of MFH come from? Slowly growing 15 cm soft
I have nothing to disclose.
Slowly growing 15 cm soft tissue mass in the thigh
Deep but does not involve bone
Biopsy at referring hospital read as “MFH”
Where did the diagnosis of MFH come from? How can we subclassify pleomorphic sarcomas? What are meaningful clinicopathologic categories of
1960s: Stout et al. multiple reports of “fibrous xanthoma” and “histiocytoma”
Cultured cells from MFH (Ozello, Stout and Murray)
Initially ameboid movement, phagocytosis histiocytes Later, bipolar spindled cells fibroblasts “Facultative fibroblasts”: histiocytes capable of fibroblast
differentiation
Kauffman SL, Stout AP. Cancer 1961 14:469-82. Ozzello et al Cancer 1963 16:331-44.
1972: Kempson and Kyriakos
Kempson RL, Kyriakos M. Cancer 1972 961-76.
Theories
Facultative fibroblasts (facultative histiocytes?) Mixture of fibroblasts and histiocytes Stem cell with dual differentiation into fibroblasts and histiocytes
Problems
No histotype supported by ancillary diagnostic and in-vitro methods Some well-differentiated tumors (liposarcoma, leiomyosarcoma, etc.)
contain areas indistinguishable from pleomorphic, storiform or giant- cell MFH
No unifying genetic changes (usually profound genomic instability)
Fletcher CD. AJSP 1992 16:213-28. Fletcher CD et al J Clin Oncol 2001, 19:3045.
Myxofibrosarcoma Leiomyosarcoma Rhabdomyosarcoma Myogenic sarcoma NOS Pleomorphic liposarcoma WD liposarcoma Osteosarcoma Myofibroblastic sarcoma Fibrosarcomatous DFSP Evans tumor Other Undifferentiated sarcoma
Fletcher CD et al J Clin Oncol 2001, 19:3045.
Undifferentiated sarcoma
Dedifferentiated liposarcoma Pleomorphic rhabdomyosarcoma MPNST Adult fibrosarcoma Pleomorphic hyalinizing angiectatic tumor Myxoinflammatory fibroblasic sarcoma Undifferentiated sarcoma
Diagnosis Clin-path clues Immunostains Genetics Sarcomatoid carcinoma Cohesive cells, clinical history, superficial near epithelium Diffuse keratin P63+ INI1 intact Melanoma Nesting, in-situ component, pigment SOX10, S100, HMB45, MelanA BRAF V600E Germ cell tumor Young patient, para-aortic, mediastinum, history SALL4, OCT4, Keratin, CD30 Hematolymphoid In nodal anatomic sites, multifocal, round cells, dyshesive LCA, CD4, MPO, CD30 Variable
Diagnosis Clin-path clues Stains Genetics Dedifferentiated liposarcoma Well differentiated component, retroperitoneum, scrotum MDM2, CDK4 Amp(12q13-15) Rhabdomyosarcoma Strap cells Myogenin, MyoD1, desmin Leiomyosarcoma Abundant dense cytoplasm Caldesmon, SMA, desmin (2 of 3) Myofibrosarcoma Loose, fasciitis-like SMA (tram-track) Pleomorphic liposarcoma Pleomorphic lipoblasts Oil red O Extraskeletal
Produces osteoid or bone SATB2 (sensitive, not specific) Malignant peripheral nerve sheath tumor NF1, pre-existing benign nerve sheath tumor SOX10, S100 (sens. ~ 50%) H3K27Me3 loss
McCormick et al Am J Surg Pathol 1994, 18:1213-23.
Horvai et al. 2009 Mod Pathol 22(S1): 14A
Leiomyosarcoma
Rhabdomyosarcoma
Myofibroblastic sarcoma
“Myogenic NOS”
Fletcher CD et al J Clin Oncol 2001, 19:3045.
Diagnosis Recurrence Metastasis Mortality Dedifferentiated liposarcoma 51% 15% 26% @ 5 yrs. Myogenic sarcomas ?% 56% 39% @ 20 yrs. Undifferentiated pleomorphic sarcoma 13-42% 31-35% 37% @ 5 yrs.
McCormick et al Am J Surg Pathol 1994, 18:1213-23. Fletcher CD et al J Clin Oncol 2001, 19:3045.
Diagnosis Clin-path clues Stains Genetics Myxofibrosarcoma Superficial, predominantly myxoid, branching vessels Nonspecific, most negative Variable Atypical fibroxanthoma / Pleomorphic dermal sarcoma Dermal, subcutaneous, sun damage Nonspecific: Vimentin, CD10; negative for keratin and melanocytic NOTCH1/2 FAT1 Pleomorphic hyalinizing angiectatic tumor Foot, middle age, damaged vessels, 0-1/10 hpf S100 negative TGFBR3-MGEA5 Myxoinflammatory fibroblastic sarcoma Acral, foot, pseudolipoblasts, inflammation, <1 mf / 50 hpf Nonspecific BRAF (in pure MIFS)
McCalmont TH. J Cutan Pathol 2011; 38:853. McCalmont TH. J Cutan Pathol. 2012 39:8.
Odei B et al. Am J Clin Oncol 2017 epub. Koch M et al. Anticancer Res 2015 35:5717. Miller K et al. Am J Surg Pathol 2012 36:1317. Folpe AL, Weiss SW. Am J Surg Pathol 2004 11:14-17. Laskin WB et al. Am J Surg Pathol 2014 38:1. Roland CL et al. Ann Surg Oncol 2016 23:2220.
Diagnosis Recurrence Metastasis Mortality Myxofibrosarcoma (grade 1-3) 31% 15% 23% @ 3 yrs. Atypical fibroxanthoma 8% 0-3% 0-2% @ 20 yrs. Pleomorphic dermal sarcoma 28% 5-10% 0-2% @ 2 yrs. Pleomorphic hyalinizing angiectatic tumor 33% 0% 0% @ 4 yrs. Myxoinflammatory fibroblastic sarcoma 51% 2% 0% @ 5 yrs. Undifferentiated pleomorphic sarcoma 13-42% 31-35% 37% @ 5 yrs.
Undifferenti- ated sarcoma
Lymphoma: DLBCL, anaplastic
Myeloid sarcoma
Follicular “dendritic cell”
Interdigitating “dendritic cell”
True histiocytic sarcoma
Cannatella J and Horvai A. Manuscript in prep
Undifferent iated sarcoma
Lymphoma: DLBCL, anaplastic
Myeloid sarcoma
Follicular “dendritic cell”
Interdigitating “dendritic cell”
True histiocytic sarcoma
Cannatella J and Horvai A. Manuscript in prep
Biopsy:
Desmin, SOX10, Keratin History of NF1: S100, H3K27Me3 Looks myoid: SMA, caldesmon If retroperitoneal, scrotal or imaging to suggest fat: MDM2, CDK4
Excision:
H&E: lipoblasts, cartilage, bone, benign neurofibroma, mitotic activity Same stains as above Make sure mitoses correlate with pleomorphism esp. in feet