Myeloid sarcoma of the gastrointestinal tract: Wolf in sheep’s clothing!

A 42-year-old gentleman presented with irregular diarrhea for last one year and pain abdomen for 14 days. Complete blood count showed: Hb = 12.1 gm/dl, TLC—21000 cells per microliter, and platelet—1.27 lakhs per microliter. Peripheral blood smear showed the presence of 70% blasts which were large, around three times the size of small lymphocyte, had irregular nuclear contours with convolutions, moderate gray–blue cytoplasm with fine vacuolations in some of the blasts, fine lacy chromatin, and inconspicuous nucleoli [Figure 1].Figure 1: Peripheral blood smear revealed atypical cells three to four times the size of small mature lymphocyte, had a high N/C ratio, irregular nuclear contours, hyperchromatic nuclei, and inconspicuous nucleoli, suggestive of blasts with monocytic differentiation (Giemsa ×600)Contrast-enhanced computed tomography revealed an ill-defined heterogeneous soft tissue mass involving the distal end of the common bile duct causing abrupt cutoff. Esophagogastroduodenoscopy revealed nodular vascular mucosa in the body of the stomach, antrum, and D2, and a biopsy was taken from both the latter sites. Histopathology showed large sized, atypical cells arranged singly and in diffuse sheets in lamina. These cells were two to three times the size of mature lymphocytes, had high N/C ratio, irregular nuclear contours, hyperchromatic nuclei, and scant cytoplasm. Some of these cells had prominent 1–2 nucleoli. Brisk mitotic activity was noted [Figure 2]. On immunohistochemistry (IHC), these atypical cells were positive for leukocyte common antigen (LCA), myeloperoxidase (MPO), CD34, and CD117, while they were negative for CD20, CD79a, CD19, CD3, CD38, Bcl-6, MUM1, ALK, CD30, CD23, Tdt, and PAX5 [Figure 3].Figure 2: (a) H and E section from duodenal biopsy shows increased intercryptal distance with diffuse infiltration in the lamina propria by atypical cells (b) On higher magnification, these cells have high N/C ratio, medium to large hyperchromatic nuclei with regular nuclear contour and inconspicuous to prominent nuclei (H and E ×200)Figure 3: On immunohistochemistry, tumor cells are diffusely positive for (a) Leukocyte common antigen (CD45) (b) Myeloperoxidase (MPO) (c) CD34 (d) CD117 (×200)The patient was further worked up for acute leukemia. Flow cytometric analysis performed on three-laser, 10-color Navios Beckmann Coulter showed 68% blasts with moderate CD45 and high side scatter (SSC). These blasts were positive for CD34, CD38, CD64, CD13, CD33, HLA DR, and MPO, and were negative for CD11b CD4, CD8, CD3, and CD79a. The cytogenetic analysis of the peripheral blood showed CBFB/MYH11 translocation and c-kit mutation [Figure 4].Figure 4: Flow cytometry plots on three-laser, 10-color Navios Beckman coulter analyzer showing 68% blasts with moderate CD45 and high side scatter (SSC). Blasts are positive for CD34, CD38, CD64, CD13, CD33, HLA DR, and MPO and are negative for CD11b, CD 4, CD 8, CD 3, and CD79a.A final diagnosis of AML with monocytic differentiation and concurrent MS involving stomach and duodenum was rendered. The patient refused for chemotherapy and succumbed to the disease within a month. Myeloid sarcoma (MS) is a rare extramedullary myeloblastic tumor with an incidence of less than 1%.[1] MS is typically reported to occur in the skin (13%–22%), bone (9%–25%), or lymph nodes (15%–25%). It is most often associated with AML (30%); less often with other myeloproliferative neoplasms like chronic myeloid leukemia and myelodysplastic syndrome, and rarely as a de novo occurrence without bone marrow involvement.[2] The gastrointestinal tract (GIT) is a rare site for MS (6.5%). Gastric MS has an incidence of less than 1%.[3] The most extensive review by Kheirkhah et al.[4] identified 61 cases of MS localized in the GIT. In a series of 27 cases of small bowel MS, none of the cases had duodenal involvement.[3] Patterson M et al. reported 13 cases of de novo MS distributed throughout GIT involving the stomach, duodenum, colon, pancreas, small intestine, and mesentery.[3,5] On the literature review, less than 15 cases of myeloid sarcoma have been reported involving the duodenum and stomach each.[2,4-6] Most of the reported cases from small intestinal MS are from ileum or jejunum. Most of the AML patients show GIT involvement during the course of the illness or during treatment. MS involving the duodenum and stomach is extremely uncommon and concurrent acute leukemia presenting primarily with GI symptoms of abdominal pain and diarrhea is even rarer. Neither the routine hematologic workup available did not reveal any atypical cells nor was there any clinical suspicion of leukemia. The histopathologic diagnosis led to a thorough hematologic workup. Imaging and endoscopy findings in these cases are usually nonspecific. GIT involvement by MS is in the form of typically a nodular and ulcerated mass or lesion. The diagnosis of primary MS is challenging with a high rate of misdiagnosis (25–75%).[5] Histopathology remains the mainstay of diagnosis and can be a diagnostic surprise for the clinicians. Careful attention must be paid to the morphology of these atypical hematolymphoid cells, which are discohesive and infiltrate singly, have a high nuclear/cytoplasmic ratio with marked nuclear irregularities and prominent nucleoli. The most common morphologic misdiagnoses are malignant lymphoproliferative disorders, including non-Hodgkin lymphoma, histiocytic sarcoma, thymoma, plasma cell myeloma, melanoma, undifferentiated round cell sarcoma, GIST, and poorly differentiated carcinoma.[4,5] An extensive armamentarium of IHC markers in an appropriate clinical context is required to exclude these differentials. Non-Hodgkin lymphoma shows positive immunoexpression for T- or B-cell lineage markers like CD3, CD4, CD19, CD20, and CD79a, poorly differentiated carcinoma is pancytokeratin positive, GIST is CD117, DOG1, and CD34 positive, and melanomas are usually HMB45 and S100 positive.[2,3] Discohesive large cells in sheets with irregular to convoluted nuclear contours and opened-up chromatin can be a clue toward hematologic neoplasm. Positive immunoexpression for the stem cell markers (CD34 and CD117) and myeloid cell lineage markers (CD33, MPO, CD68, CD163) in the blasts is confirmatory for MS.[5] The literature review reveals that the majority of MS cases with GIT involvement featured positive expression of either CD34 (91%, n = 36) or CD117 (93%, n = 29).[4] Only a single report was identified with a negative expression of both of these markers.[7] Further, the expression of either CD43 (94%, n = 17) or MPO (97%, n = 32) serves as another sensitive marker. Aberrant expression of lymphoid markers, like CD3 and CD79a, can be rarely seen.[4] The possibility of benign extramedullary hematopoiesis (myeloid metaplasia) should also be kept in the differential diagnosis; however, that is characterized by multilineage hematopoietic elements showing progressive stages of maturation. CBFB/MYH11 fusion detected in our patient has been commonly reported in AML with monocytic differentiation and has shown a high predilection for GIT.[3] In a large series, 31 (94%) of 33 cases of myeloid sarcoma harbored CBFB/MYH11 fusion with a marked predilection for abdominal sites.[4,8] While this fusion has a favorable prognosis in AML, the coexistence of c-kit mutation imparts a worse prognosis. To conclude, we report a rare case of duodenal and gastric MS concurrent with AML who was diagnosed in lieu of GI symptoms. Awareness and careful evaluation of morphology is utmost and an extensive immunohistochemistry panel is necessary for establishing the diagnosis and initiating timely systemic chemotherapy. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.