Histology Favorable: <1 yr age, hyperdiploid, lack of n-myc
Unfavorable: 1p36 del (n-myc amplification >10 times), diploidy, del(14p), high Mitosis-Karyrhexis index, >1 yr age
t(2;13) PAX3 / FKHR and t(1;13) PAX7 / FKHR - PAX3 and 7 members of paired box family trsc factors, FKHR member of forkhead trsc factor family. Fusion protein is potent trsc activator.
Occur in all ages, more often in juven and adult. Arise in extremities, no favored site.
Three histologic subtypes: typical, solid and mixed embryonal and alveolar. All mimic lymphoma but with primitive myoblastic diff. Typical with fibrovasc septae separate tumor cells into nests. Cell align septae in picket fence pattern, discohesion in center.
High grade, more aggressive than embryonal.
Desmoplastic small round cell tumor
t(11;22) WT1/EWS- fusion of the Ewings sarcoma gene with the wilms tumor gene. WT-1 expressed in mesodermal tissues- hence serosal lining involvement. EWS- trsc modulation, WT-1 - DNA binding domain
Children and young adults, widespread abdominal serosal involvement, striking male predominance.
Small round cell tumor with prominent stromal desmoplasia and polyphenotypic diff. Epithel, muscle, and neural diff characteristic
IHC: strong positive with cytokeratin, desmin, NSE. Myogenin negative. WT1 usually positive.
Prognosis very poor.
Alveolar soft part sarcoma
t(X;17) ASPL/TFE3 - TFE trsc factor fused with ASPL gene, localize to nucleus and activate trsc.
Most common 15 - 35 yrs. Extremities, deep soft tissue of thigh. Children - head and neck region
Organoid nesting pattern composed of large, uniform, epithelioid cells with granular eosinophilic cytoplasm. Nests separated by thin sinusoids. PAS w/diastase stains rhomboid crystals in cytopl. Also seen in EM.
IHC: nuclear staining positive for TFE. Otherwise, no consisent positive findings
Prognosis: Slow growing yet highly metastatic.
t(17;22) COL1A1/PDGF beta- fused collagen gene with platelet derived growth factor- fusion protein is potent growth factor.
Young to middle aged adults, trunk or extremities.
Infiltrative, deep dermal and subcutaneous proliferation of monotonous, bland spindle cells in a distinct storiaform pattern. Infiltrate subq fat in lace-like pattern. Wrap around adnexa. Pigmented variant - Bednar tumor with melanin-laden dendritic cells.
IHC: CD34 positive, s100 and F13a negative
Childhood variant - giant cell fibroblastoma
Prognosis- locally aggressive, mets uncommon (5%)
Congenital mesoblastic nephroma (cellular type)
t(12;15) same as infantile fibrosarcoma, ETV6(TEL)/NTRK3- activation of NTRK3 receptor tyrosine kinase. Infantile fibrosarcoma arising within kidney.
Classic (non-cellular) type not related to infantile fibrosarc, insecting bundles of spindle cells, less dense, thin walled vasc spaces, less mitotic activity, sharply demarcated border.
IHC: actin and vimentin positive, cd34/s100/keratin negative
t(12;15) ETV6(TEL)/NTRK3- activation of NTRK3 receptor tyrosine kinase. Also trisomies 8,11,17 and 20.
<2 yrs age, superficial and deep soft tissue of distal extremities
Intersecting fascicles of primitive ovoid to spindle cells with herringbone pattern. Zone necrosis and hemorrhage frequent. Little pleomorphism.
IHC nonspecific, vimentin positive
Favorable outcome when compared to the adult fibrosarcoma.
Extraskeletal myxoid chondrosarcoma
t(9;22) CHN(NR4A3)/EWS in approx 50% of cases, produces fusion oncoprotein.
Rare, adulthood, deep soft tissue of prox extremities and limb girdles.
Multinodular architecture, abundant myxoid matrix and malignant chondroblast-like cells arranged in cords, clusters, or delicate networks. No convincing evidence of chondroid diff. Cells typically show low grade cyto features.
IHC: vimentin positive, no other consistent.
Possible of prolonged survival, but known to have high risk local recur and mets.
t(12;16) FUS/CHOP - present in >90% cases. Fusion oncoprotein.
Second most common liposarcoma, young adults, deep soft tissue of extremities, thigh.
Uniform round to oval primitive non-lipogenic mesenchymal cells and variable small signet ring lipoblasts in a prominent myxoid stroma with characteristic branching vascular pattern (pulmonary edema like). Round cell areas (>=5%) defined as solid sheets of back to back primitive round cells with high NC ratio and no intervening stroma.
t(12;22) ATFI/EWS- fusion protein represses p53 activation
Rare, young adults, extremities with predilection for foot/ankle. Usually deep seated around tendons (malignant melanoma of soft parts)
Typical uniform, nested or fascicular growth pattern of polygonal to spindle cells with abundant eosinophilic/clear cytoplasm. Thin fibrous septae around nests.
IHC: positive for s100, HMB45 and other melanoma antigens.
t(X;18) SSX1/SYT and SSX2/SYT
SSX1 biphasic, SSX2 monophasic
-22 or del(22q)
del(1p) or (14q) - anaplastic
Clear cell RCC
-Y, +7, +17, t(X;1)
TFE translocation RCC
t(X;1) PRCC/TFE1 and t(X;17) ASPSCR1/TFE1
Acute myelogenous leukemia
t(8;21) (RUNX1T1)ETO/(RUNX1)AML - M2 morphology/with maturation, younger pts, and good response to tx, longterm dz-free survival
Characteristic high expression CD34/HLA-DR/MPO and CD13, weak CD33. Frequent CD19 and PAX5
inv(16), t(16;16) CBFB/MYH11 - M4 morphology?/Monocytic and granulocytic diff and abnl eos granules in BM, younger patients more common, good prognosis in young, worse in older pts
t(15;17) PML/RARA - M3 morphology, hyper and hypogranular (WBC very high) types, good response to ATRA, DIC, best prognosis of AML
Hypergranular: low expression CD34, HLA-DR, CD11a, 11b and CD18 and bright expression CD33, heterogenous CD13, CD117 (sometimes weak).
Hypogranular: frequent expression of CD34 and CD2
CD56 expression associated with worse outcome
t(11;17) PLZF/RARA - variant APL, poor response to ATRA
t(6;9) DEK-NUP214 - with or without monocytic features, basophilia and multilineage dysplasia, nonspecific phenotype, poor prognosis
t(3;3) or inv(3) RPN1-EVI1- nl or elevated plts, atypical megakaryocytes, arise from MDS or de novo, adults most common, poor prognosis
t(1;22) RBM15-MKL1- maturation in megakaryocyte lineage (M7), infants with Downs female, prognosis unclear
CD41 (glycoprot 2b3a), CD61 (glyco 3a), CD42 less frequent, myeloid may be positive, 34, 45 and DR often negative. CD36 positive
t(9;11) MLLT3-MLL - monocytic features, more common in young, 11q23abnl, DIC, tissue infiltration, intermediate survival, CNS involvement
Strong expression of CD33, CD65, CD4 and HLA-DR, low expression of CD13,34 and 14. Plus markers of monocytic origin
Myelodysplastic syndrome with isolated del(5q)
Sole genetic abnormality is del(5q). Elderly women, with severe macrocytic anemia and occasional thrombocytosis. Medial survival 145 months (>10yrs), transformation <10%
Chronic myelogenous leukemia
t(9;22) BCR (chr 22)/ABL (chr 9) fusion gene p210 (90-95%) on Ph chromosome, increased tyr kinase activity. Imatinib competes for ATP binding site of fusion protein. Indolent chronic phase, accelerated phase and blast phase. Older adults. Neutrophil leukocytosis in different stages of maturation, no sig dysplasia, absolute basophilia. Progression to blast phase associated with clonal evolution: extra Ph chr, +8, +19 or i(17q).5 yr progression free survival 80-95%.
B lymphoblastic leukemia/lymphoma
Hyperdiploidy (>50 chromosomes and usually <66 chromosomes) - very favorable prognosis, cures >90% of children
CD10/19/34 positive, often CD45 negative
t(12;21) TEL(ETV6)-AML(RUNX) - common in children ~25% B-ALL, very favorable prognosis, >90% cure
Hypodiploidy - blasts with <46 chromosomes, children and adults, poor prognosis, 44-45 chromosomes do better then less
t(v;11q23) most common t(4;11) MLL - most common leukemia in <1 yr, CNS, neonates and infants, poor prognosis
CD10 negative, CD24 negative, CD15 and CD19 positive
t(1;19) E2A(TCF3)-PBX1- children, poor prognosis?
CD10/19/ mu heavy chain positive
t(9;22) BCR-ABL - worst prognosis in patients with ALL, p190 kd BCR-ABL fusion protein (in all kids and 1/2 adults)
CD10/19/Tdt positive, occ CD13,33, 25
t(8;14) cMYC/IgH and t(8;22) cMYC/IgLambda and t(2;8) IgKappa/cMYC (up to 10% of cases lack MYC translocation)- endemic form: equatorial africa, most common childhood malig, EBV in all patients. Sporatic form: worldwide, children and young adults, EBV in 30%.
CD10, CD19, CD20, CD22, CD38, CD43, CD77, BCL-6, weak or negative BCL-2, Tdt negative. Near 100% ki67 index. High cure rate in low stage disease.
t(14;18) BCL2/IgH (90% cases) - widespread dz at dx, US and West Europe, adults, paratrabecular involvement in BM, grade 1-2 indolent, grade 3 more aggressive.
Mantle cell lymphoma
t(11;14) BCL1 (cyclin-D1)/ IgH - mid to old adults, LN spleen BM plus upper GI tract. Blastoid and pleomorphic variants- poor prog. Survival 3-5 yrs.
CD5, FMC-7, cyclin D- and CD43 positive, weak to negative CD23, negative for CD10 and BCL-6.
Extranodal marginal zone (MALT) lymphoma
t(11;18) MALT/API2 in pulmonary and gastric tumors, t(1;14), t(14;18) in ocular adnexae and salivary gland, and t(3;14) in thyroid, skin, orbit- indolent nature, t(11;18) resistant to H.pylori eradication
CD20, CD79a and weak CD43, 11c positive, CD5, CD10, CD23 negative. CD21 and CD35 also expressed.
Plasma cell myeloma
Hyperdiploidy >45 and <65 chromosomes - good prognosis
t(11;14) CCND1/IgH - most common, good prognosis
del(13), del(17p), t(4;14), t(4;16) or t(14;20) - poor prognosis
t(8;14) cMYC/IgH - poor prognosis
hypodiploid - poor prognosis
Anaplastic large cell lymphoma
t(2;5) ALK-NPM, strong nuclear and cytoplasmic ALK staining, 85% of cases
t(1;2) TPM3-ALK, 13% of cases
ALK+ patients have favorable prognosis(80% 5yr) compared with ALK negative cases (48%)