Myeloid sarcoma.pptx

Myeloid Sarcoma

1. Myeloid sarcoma Speaker: Snehvarsha Bhagat Moderator: Dr. Pulkit Rastogi

2. Definition: A myeloid sarcoma is a tumor mass consisting of myeloid blasts, with or without maturation, occuring at a site other than the bone marrow. Infiltration of any site of the body by myeloid blasts in a patient of leukemia is not classified as myeloid sarcoma unless it presents with tumor masses in which the tissue architecture is effaced. Also known as : Granulocytic sarcoma Chloroma Extramedullary myeloid tumor

3. EPIDEMIOLOGY: Predilection for males and older individuals Male:female = 1.2:1 Median patient age:56 yrs Rare neoplasm with difficulty encountered in its treatment. ETIOLOGY: Similar as that of AML and other myeloid neoplasm like MDS and MPN De novo mostly May be therapy related Developmental Anomaly • Patients with certain inherited diseases have increased risk of AML/MS ○ Fanconi anemia , Down syndrome, Klinefelter syndrome, ataxia-telangiectasia, neurofibromatosis Environmental Exposure • Ionizing radiation • Chemotherapy with cytotoxic agents and topoisomerase II inhibitors • Chemicals, such as benzene, pesticides, and herbicides

4. LOCALIZATION: Any site. Most commonly- skin, lymph nodes, GIT,bone,soft tissue and testes. ○ Skin: 28-43% ○ Lymph node: 16-22% ○ Central nervous system: 3-9% ○ Testis: 7% ○ Intestines: 7% ○ Bladder: 4% ○ Gynecologic tract: 4% ○ Pleura and chest wall: 4% ○ Bone: 3% ○ Multiple anatomical sites: < 10% of cases

5. CLINICAL settings: 1)In about 25%cases, myeloid sarcoma occurs in absence of an underlying AML or other myeloid neoplasm - here, its detection is considered equivalent to diagnosis of AML. 2)May precede or coincide with AML or constitute Acute blastic transformation of MDS, MDS/MPN or MPNs. 3)Isolated Myeloid Sarcoma occurs in 8-20% of patients with Allogenic Stem Cell Transplantation. 4) Initial manifestation of relapse in a patient with previously diagnosed AML, regardless of blood or bone marrow findings. 5)Associated with a simultaneous or previously treated NHL ( Eg. - Follocular Lymphoma, Mycosis fungoides or Peripheral T cell lymphoma, NOS) Or with a previous histoy of non haematopoietic tumor ( Eg. - Germ cell tumor, prostatic carcinoma, endometrial carcinoma, breast cancer or intestinal adenocarcinoma).In this setting, myeloid sarcoma might be secondary to prior chemotherapy.

6. Gross pathology: • MS with granulocytic differentiation is designated as chloroma because tumors have green color ○ Green is result of verdoperoxide – Peroxidative enzyme present in cytoplasmic granules of MS

7. Picture 1: Chloroma of oral cavity Picture 2: Isolated Myeloid Sarcoma presenting with small bowel obstruction

8. Picture 1: Myeloid Sarcoma Presenting With Multiple Skin and Subcutaneous Mass Without Leukemic Manifestations After Renal Transplantation Picture 2 : chloroma of bone

9. MICROSCOPY: The tumor consists of blasts with scant cytoplasm and round- oval nuclei with finely dispersed chromatin and minute but distinct nucleoli. Mitotic figures are numerous. The tumors may have: 1) Myeloblasts (most common) with or without features of promyelocytic or neutroplic matutation . 2) Myelomonocytic morphology 3) Pure Monoblastic morphology 4) Erythroid precursors (rare) 5) Megakaryoblasts (rare) Architecturally, at extranodal sites, neoplastic cells frequently mimic metastatic carcinoma by forming cohesive nests and/ or single files surrounded by fibrotic septae . In lymph node, they can either infiltrate the paracortex surroundind reactive follicles or grow diffusely, often extending into perinodal fat.

10. Light microscopic picture of Myeloid Sarcoma.

11. Microscopic picture of myeloid sarcoma infiltrating maxillary muscle.

12. CYTOCHEMISTRY: • Touch imprints are very helpful ○ Wright-Giemsa stain allows assessment of morphologic features as seen in bone marrow ○ Unstained, air-dried imprints can be used for cytochemistry On imprints, cytochemical stains can be used to differentiate between- Granulocytic lineage forms { MPO +, naphthol AS-D chloroacetate esterase CAE+} and Monoblastic forms {Non specific Esterase +} SECTION

13. IMMUNOPHENOTYPE: MS expresses array of myeloid-associated antigens • CD68/KP-1(+), lysozyme (+), CD43(+) > 95% • Myeloperoxidase (+): ~ 90%; CD117(+): ~ 80% On IHC in parrafin sections, tumors express CD33,CD34,CD68 (KP1 but not PGM1)and KIT(CD117 ).Staining for TdT , MPO and CD45 is inconsistent. Promyelocytic tumors : CD34 -, TdT –, MPO +, CD 15 + Myelomonocytic tumors : Homogenously + for CD68/KP1. MPO and CD68/PGM1(or CD163) confined to distinct subpopulations, which are CD 34+ Monoblastic tumors : CD68/PGM1 + , CD163+, MPO -,CD34 – Erythroid tumors : Strong + glycophorin A and C, haemoglobin and CD71. Megakaryoblastic tumors : CD61+, LAT +, vWF +

14. CD99 + in >50% cases without association with a specific subtype ~20% show variable degree of CD56 expression More often in inv(16) cases, foci of plasmacytoid dendritic cell differentiation is seen with CD123 +, CD303 + and CD56 – ~16% of tumors stain for NPM1 at the nuclear and cytoplasmic level – indicate presence of NPM1 mutations. Cases which meet criteria for mixed phenotype Acute leukemia are not classified as Myeloid Sarcoma. FLOW CYTOMETRIC ANALYSIS: Tumors with myeloid differentiation : + for CD13, CD33, KIT,MPO Monoblastic tumors : + for CD14,CD163, CD11c

15. CD 3 - CD20 - MPO + CD 34 + CD 45 + CD 117 +

16. DIFFERENTIAL DIAGNOSIS: 1) MALIGNANT LYMPHOMA . Cytochemical and immunonophenotypic analyses help to differentiate myeloid sarcoma from B and T lymphoblastic leukemia/lymphoma, Burkitt’s ,DLBCL, small round cell tumors in children. 2) NON EFFACING EXTRAMEDULLARY BLASTIC PROLIFERATIONS ;which occur in AML or in conjunction with acute transformation of MPN,MDS or MDS/MPN. 3) EXTRAMEDULLARY HAEMATOPOIESIS ,following the administration of growth factors that can produce pseudotumoral masses in any part of body. 4)In ADVANCED STAGE MPN , nodular accumulations of mature hematopoietic cells occur. Trilineage haematopoiesis and lack of a significant blast component confirm extramedullary haematopoiesis and exclude myeloid sarcoma 5) BLASTIC PLASMACYTOID DENDRITIC CELL NEOPLASM

17. 6)HISTIOCYTIC SARCOMA: Cells of histiocytic sarcoma are larger, cytoplasm is more abundant and evidence of blood or bone marrow involvement in patients with histiocytic sarcoma DIAGNOSTIC CHECKLIST: • High index of suspicion needed to diagnose MS • Green color of gross specimen ○ Medium-sized or large cells with blastic chromatin, folded nuclei, high mitotic rate ○ Intracytoplasmic granules (myelocytes)

18. GENETIC PROFILE : ~55% cases show chromosomal aberrations detected by FISH/ cytogenetics These include monosomy 7;trisomy 8; KMT2A rearrangement; inv(16); trisomy 4; monosomy 16; loss of 16q,5q,or 20q; and trisomy 11 . ~16% cases carry NPM1 mutations , show aberrant cytoplasmic NPM1 expression.Such cases mostly have myelomonocytic or monoblastic morphology. t(8;21)(q22;q22)is observed more in paedeatric population than adults. inv(16) or amplification of CBFB has been linked to breast, uterus or intestinal involvement and possible foci of plasmacytoid dendritic cell differentiation. Trisomy 8 and KMT2A –MLLT3 fusion seen more often in myeloid sarcoma involving skin and breasts.

19. PROGNOSIS AND PREDICTIVE FACTORS: Clinical behaviour and response to therapy do not seem to be influenced by age, sex, anatomical site, type of presentation, therapy relatedness, histologic features, immunophenotype or cytogenetic findings. Radiotherapy or surgery is sometimes used upfront in patients who need debulking or rapid symptom relief. Patients who undergo allogenic or autologous bone marrow transplantation seem to have higher probability of prolonged survival or cure.

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