Dysplastic megakaryocytes and eosinophilic precursors in the diagnosis


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  • ***If untreated, many of these patient go on to develop AML within less than 1 year.
  • Ten cases of granulocytic sarcoma was reported. This table shows the various clinical, pbs ,fnac finding along with the diagnosis and follow up..
  • Cmpd-chronic myeloproliferative disease
  • This is picture of lympmh node fanac showing dysplaticmegakayocyte with myeloid precursor
  • Mpd-myeloprolifertave disease
  • Mds-myelodysplastic syndrome
  • Mpd-myeloproliferative disease.
  • Mpd- myeloproliferative disease
  • Autoimmune pancreatitis (AIP
  • Only those patients with a prior FNA of the pancreas were included.
  • Demographic characteristics included 12 males and 5 females with age ranging from 29 to 76 years. The patient were predominantly white-13, with 2 asian patients, 1 african –american ,and 1 patient listed as others.
  • Most common presenting symptoms wereAbdominal pain in 41%Obstructive jaundice in 29%.The remaining patients presented with pancreatitis.weight loss early satiety and irritable bowel.
  • Aip-autoimmune pancreatitis.
  • Of the 20 aspirates,1 was diagnosed as adenocarcinoma, 1 as suggestive of mucinous cystic neoplasm, 10 as atypical, 5 as benign and 3 as scant or nondiagnostic.
  • The single igg4 negative case was noted to have granulocyte – epitheliallesions,which are found in a subset of AIP without elevated IgG4 levels
  • AIP- autoimmune pancreatitis.
  • AIP- autoimmune pancreatitis.
  • AIP- autoimmune pancreatitis.
  • Autoimmune pancreatitis (AIP
  • AIP- autoimmune pancreatitis.
  • Dysplastic megakaryocytes and eosinophilic precursors in the diagnosis

    2. 2. INTRODUCTION  Myeloid sarcoma is a rare manifestation characterized by the occurrence of 1 or more tumorous myeloid masses at an extramedullary site.  It is also known as extramedullary acute myeloid leukemia (AML), extramedullary myeloid tumor, myeloblastoma, granulocytic sarcoma or chloroma.
    3. 3.  Myeloid precursors on fine-needle aspiration can be seen in a variety of pathological states, both neoplastic and nonneoplastic.  Myeloid sarcoma can precede, occur concurrently, or arise subsequent to the diagnosis of AML.  It can also arise in patients with myelodysplastic syndrome, chronic myeloproliferative disease and myelodysplastic disease.  The incidence of myeloid sarcoma ranges from 1 to 3%.
    4. 4.  The most common sites of myeloid sarcoma are the subperiosteal bone structures of the skull, paranasal sinuses, bones, lymph nodes, and skin.  Less common sites are central nervous system, spinal cord, breast, heart, thymus, liver, spleen, pancreas, endocrine glands and female genital tracts.
    5. 5.  1) 2) 3) Myeloid sarcoma occurs in patients with AML in three clinical settings: Most often, myeloid sarcoma is associated with concurrent evidence of AML involving the blood and bone marrow. Myeloid sarcoma can arise in patients with a history of AML as a sign of relapse. Least frequently, myeloid sarcoma can arise in patients without a history or concurrent evidence of AML.
    6. 6.  Myeloid sarcoma can show unilineage or multilineage proliferation and is further sub classified within the WHO scheme as differentiated, immature, and blastic.  Differentiated tumors are composed of numerous promyelocytes and more mature granulocytic cells.  Immature tumors are composed of myeloblasts, promyelocyte and blastic tumors which is least mature.  They are composed predominantly of myeloblasts with little evidence of granulocytic differentiation.
    7. 7.  Proliferation of the erythroid or megakaryocytic series can also be seen in myeloid sarcoma, most often in cases with chronic myeloproliferative disease or myelodysplastic syndrome.  Megakaryocytes may be dysplastic, small or abnormally large in size with hyper or hypolobated nuclei, or show hyperchromasia.  Thus, the presence of immature myeloid cells, eosinophilic precursors or dysplastic megakaryocytes is supportive of the neoplastic nature of a myeloid proliferation.
    8. 8. MATERIALS AND METHODS  During the course of study nearly 4186 FNAC of lymph nodes were performed.  186 were diagnosed as hematolymphoid malignancies of which 15 cases were diagnosed as myeloid sarcoma with the involvement of lymph node in 10 cases.  FNAC was performed using 23- gauge disposable needle and 10 ml disposable syringe. Both non-aspiration and aspiration techniques were used.  Peripheral smears of all cases were made by using finger prick technique and stained with Giemsa stain.
    9. 9. RESULTS  The differentiation of granulocytic sarcoma from malignant lymphomas and other small round cell tumors is very critical.
    10. 10.   Location of Extramedullary Proliferation: In this, 7 patients presented with multiple lymphadenopathy and 3 patients with enlargement of a single group of lymph nodes.  The majority of the patients (8 cases) presented with cervical lymphadenopathy and 6 of these also showed inguinal and axillary lymphadenopathy.  One case had isolated inguinal lymphadenopathy and the other had multiple lymph nodes involving inguinal, axillary, pre and para -aortic groups.
    11. 11. CLINICAL PRESENTATION  Four patients were less than 20 years of age,3 were in the age group of 21-40, 2 were between 41 and 60 and 1 was more than 60 years of age.  The male: female ratio was 2:1.  Six patient had fever at the time of presentation,4 had hepatosplenomegaly of moderate grade,4 had symptoms related to anemia, 1 patient had skin lesions and 1 had gum bleeding.  Pre- FNAC diagnosis of a neoplastic process was present in only 2 cases (1 case of AML and 1 of CML).  In all other cases, diagnosis was confirmed by examination of peripheral smear, bone marrow examination, flow cytometry or cytogenetics.
    12. 12. LABORATORY FINDINGS  Complete Blood count and Peripheral Blood Smear  Total white blood cell count was raised in 8 cases, normal in 1 case and decreased in 1 case. Peripheral blood smears of all patients were taken and stained with Giemsa stain. Eight cases showed the presence of blasts or myeloid precursors in the peripheral blood. Three of the 8 cases showed an AML –like picture with blasts> 20% and 4 cases showed features of CMPD with immature myeloid precursors, eosinophils and eosinophilic precursors, occasional basophils and blasts < 10%. One case showed atypical monocytoid cells without cytoplasmic granularity on PBS.    
    13. 13. FNAC FINDINGS:  1. 2. 3. Cytological findings that suggested the diagnosis were: The presence of immature myeloid series cells, especially eosinophilic precursors. Blasts with cytoplasmic granularity. Dysplastic megakaryocytes.
    14. 14.  Megakaryocytes with dysplastic forms were seen in 5 of the10 cases(2 CML, 1 AML and 2 cases where PBS do not show blast) and in conjugation with eosinophilic precursors helped in the diagnosis of myeloid sarcoma.
    15. 15. FOLLOW- UP  In this study, there were 10 patients where myeloid precursors were seen on fine- needle aspiration of lymph nodes and were diagnosed as myeloid sarcoma.  On further investigations, 3 cases were diagnosed as CML on PBS.  1 case was diagnosed as juvenile myelomonocytic leukemia, as the LAP(leukocyte alkaline phosphatase) score was 18 (normal range 20-180) and the Philadelphia chromosome was negative; 2 cases did not show lasts on PBS, however one of them was diagnosed as MPD on bone marrow aspirate.
    16. 16. DISCUSSION  Myeloid sarcoma of the lymph node is an uncommon entity and should be distinguished from myeloid metaplasia and Non- Hodgkin lymphoma.  Extramedullary hematopoiesis (EMH) or myeloid metaplasia can occur in the lymph nodes of children with benign hematological disorders like: Thalassemia Hereditary spherocytosis Sickle cell anemia Congenital dys-erythroblastic anemia Immature thrombocytopenic purpura     
    17. 17.  Extramedullary hematopoiesis can show either unilineage or multineage proliferation like myeloid sarcoma.  The presence of myeloid precursors including blasts, eosinophilic precursors and dysplastic megakaryocytes is not seen with extramedullary hematopoiesis.  This favors a diagnosis of extramedullary hematopoiesis. myeloid sarcoma over
    18. 18.  Myeloid sarcoma can closely resemble diffuse large cell lymphomas of B cell or T cell lineage and without clinical history and high index of suspicion are likely to be misdiagnosed.  Cytologically, diffuse large B cell lymphoma have one or more prominent nucleoli and thick nuclear membranes.  Myeloid sarcomas have eosinophilic myelocytes or other myeloid precursors which differentiate it from non-Hodgkin lymphoma.  Blasts in myeloid sarcoma also show cytoplasmic granularity which is absent in non- Hodgkin lymphoma.
    19. 19.  In the study, 1 case which showed atypical monocytoid cells and eosinophilic precursors on FNAC was diagnosed on flow cytometry as pre-T ALL.  Pre-T ALL is usually infiltrated by eosinophils and some of these cases have developed AML, MDS or myeloid sarcoma, suggesting that both neoplasm arise from common progenitor cell.
    20. 20.  Two cases had a normal PBS, but the presence of eosinophilic precursors and dysplatic megakaryocytes in both of them favors a diagnosis of myeloid sarcoma over extramedullay hematopoiesis.  However, myeloid sarcoma can precede diagnosis of AML or other MPD.
    21. 21.  Thus, the presence of eosinophilic myeloid precursors and dysplastic megakaryocytes in aspirates should suggest a diagnosis of myeloid sarcoma, even in the absence of a documented myeloproliferative disease.
    23. 23. INTRODUCTION  Autoimmune pancreatitis (AIP) is an inflammatory disease of the pancreas characterized by a duct-centric lymphoplasmacytic infiltrate and fibrosis.  It is a benign condition that is often treated by nonsurgical methods such as corticosteroid therapy.  Patients with autoimmune pancreatitis have elevated level of serum IgG4 which can aid in the preoperative diagnosis of the disease.
    24. 24.  AIP commonly presents with obstructive jaundice or weight loss.  It can form a mass-like lesion in the head of the pancreas.  AIP and ductal adenocarcinoma is challenging in the absence of a tissue diagnosis.
    25. 25. MATERIALS AND METHODS  • • Case Selection: The search criteria ‘autoimmune pancreatitis’ and ‘ lymphoplasmacytic sclerosing pancreatitis’ were used to identify surgical pancreatic specimens. Following clinical and pathologic data were collected for each case. Age, gender, ethinicity, presenting symptoms , date and results of preoperative imaging studies, including radiographic impression of a mass and biliary cytology.
    26. 26. CYTOPATHOLOGY  Material was obtained by transabdominal ultrasound or endoscopic ultrasound-guided FNA.  Direct smears were prepared and stained with Diff Quick as well as wet-fixed for Papanicolaou staining.  The cytologic criteria used to define ductal atypia included the presence of nuclear abnormalities such as: Hyperchromasia Irregular nuclear borders An increased nuclear-to-cytoplasmic ratio Architectural abnormalities such as the presence of disorganization within tissue fragments.    
    27. 27. SURGICAL PATHOLOGY  Specimens were processed using standard methods and stained with hematoxylin and eosin.  Based on the diagnosis determined at the time of original evaluation, the surgical and cytopathologic data were collected.  The results of IgG4 immunolabeling were available for 10 surgical cases.
    28. 28.  IgG4 immunolabeling was performed on a Ventana XT benchmark automated stainer.  Antigen retrieval was done using enzyme Protease 1 for 8 min.  Incubation with mouse anti-human IgG4 was performed for 8 min at room temperature followed by an amplification step.
    29. 29.  Hematoxylin counterstain was applied to all sections before dehydration.  A surgical specimen was determined to have increased IgG4– positive plasma cells if > 10 IgG4- positive cells were present per high power field.
    30. 30. RESULTS  A total of 20 FNAs from 17 patients were identified.
    31. 31.  Fifteen patients were diagnosed with AIP based examination of a surgical resection specimen. on  Two were diagnosed by a combination of clinical history.  The surgical resections included eight Whipple resections, four distal pancreatectomies, four surgical biopsies and one Frey procedure.
    32. 32.  Of the 10 aspirates diagnosed as atypical ,the majority were described as having rare, focal, or scattered atypical ductal cells while 1 was suspicious for malignancy, 1 could not exclude a neuroendocrine neoplasm, and 1 was makedly atypical.
    33. 33.  Common findings included hypocellularity with a smear background lacking red blood cells.  Rare, oval-shaped fibroblastic nuclei or fragments of fibrous tissue were identified.
    34. 34.  Seven of the 20 pancreatic FNA were accompanied by separate biliary cytology.  Of these specimens, one was diagnosed as markedly atypical and suspicious for malignancy.  IHC labeling for IgG4 was performed on the surgical specimens.  9 out of 10 cases demonstrating increased numbers of IgG4positive plasma cells.
    35. 35. DISCUSSION  AIP is defined as a mixed inflammatory cell infiltrate centered on the pancreatic ducts with an associated venulitis.  It is important to distinguish between pancreatic ductal carcinoma and AIP since they have overlapping clinical and radiological features.  The most common cytomorphological findings of AIP included cellular stromal fragments and inflammatory cells, present either within the stroma or in the background.  In this study, pancreatic FNA of AIP most frequently led to an ‘atypical’ cytopathologic interpretation.  The presence of significant epithelial atypia was often limited to a few or scattered groups of ductal cells.  This is due to the surrounding inflammatory and fibrotic process.
    36. 36.  In the cases available for review ,the most common findings were hypocellular background lacking red blood cells.  Fragments of fibrous tissue and focally atypical ductal epithelium were frequently seen.  Inflammatory cells were not observed in majority of cases.
    37. 37.          AIP is considered one of several manifestations of systemic IgG4- related disease. They may affect diverse organs including: Bile duct Salivary gland Lacrimal gland Retroperitoneum Aorta Lung Kidney
    38. 38.  Extrapancreatic manifestations, including sclerosing cholangitis, appear to be more commonly associated with the lobulocentric pattern of AIP.  Also, majority of the accompanying biliary cytology specimens were found to be benign.  Elevation of serum IgG4 is invariably associated with AIP, thus immunolabeling for IgG-positive plasma cells on histologic sections has become a key diagnostic tool.
    39. 39.  Based on the result of the present study, this ancillary technique may prove most useful in cases with worrisome but inconclusive atypia or scant cytologic material.  In such cases performing IgG4 immunolabeling on the cell block material may demonstrate elevated IgG4 – positive plasma cells, providing an important clue to correct diagnosis and altering the patient’s treatment course.