Extramedullary Acute Myeloid Leukemia: Testicular Myeloid Leukemia, Leukemia Cutis with Leptomeningeal Involvement

Extramedullary Acute Myeloid Leukemia: Testicular myeloid leukemia, leukemia cutis with leptomeningeal involvement Z Saeed, H Aslam, A Weil, M Muzaffar Myeloid sarcoma also called granulocytic sarcoma, myeloblastoma, or chloroma is an extramedullary tumor of immature granulocytic cells. Extramedullary soft tissue manifestations are relatively rare in hematological malignancies. One of the rarest manifestations is myeloid sarcoma (MS). MS develops as part of acute myeloid leukemia, myeloproliferative neoplasm, or myelodysplastic syndrome or at relapse, especially following allogeneic hematopoietic stem cell transplant. Demographically, it has a slight male predominance with a male to female ratio of 1.2: 1. It may occur at any age and any site in the body leading to varied clinical presentations. The most reported sites are lymph nodes, skin and soft tissues, bone, testes, gastrointestinal tract, and peritoneum. 44 year old male with past medical history of diabetes mellitus type 2 and morbid obesity presented with right testicular pain and swelling and underwent radical orchiectomy. Pathology reported seminoma and received adjuvant Carboplatin for pT3 disease. He developed left testicular pain and swelling 2 months later and underwent left radical orchiectomy. Pathology reported CD4+, CD56+ high grade hematopoietic neoplasm. It was sent for second opinion to NIH and was consistent with myeloid sarcoma with monoblastic features. Repeat evaluation of right testicular specimen was CD45+. Bone marrow biopsy showed normocellular marrow with multilineage hematopoiesis. PET scan showed hyper metabolic activity in the right hemi scrotum, widespread osseous areas of increased uptake and 3 soft tissue nodules within the subcutaneous tissues of the left abdominal wall. FNA of the subcutaneous nodule showed CD56 positive monocytoid cells. Induction chemotherapy with 7+3 (cytarabine 200 mg/m2, daunorubicin 60mg/m2) with gemtuzumab 3mg/m2 on day 1, 4, 7 was completed. Cerebrospinal fluid studies (CSF) showed monoblastic/monocytic proliferation and received intrathecal (IT) chemotherapy alternating between methotrexate and cytarabine every week. CSF studies were cleared after 2 IT chemotherapy. Patient remained in the hospital for 87 days due to poor count recovery and development of pulmonary embolism. Myeloid mutation screening identified a mutation in NRASG13D. Repeat PET scan showed 7 areas of hypermetabolic foci involving nodular densities of bilateral lower anterior abdominal wall. One of the lesion was biopsied that was negative. He completed 2 cycles of high dose cytarabine for consolidation but had repeated hospital admissions and therapy was switched to azacytidine and venetoclax. Patient was evaluated by bone marrow transplant team. He had disease progression at tenth month when he presented with severe back pain and lower extremity weakness. MRI brain and spine showed new patchy T2 hyperintense signal in the right frontal white matter, increased number and size of marrow replacing lesions throughout the visualized skeleton. Patient underwent bone biopsy that showed >90% marrow involvement (sheets of infiltrative cells with identical phenotype. Positive for CD56 (>90% of marrow cellularity), CD4 and lysozyme. Hospital course was complicated with renal failure, electrolytes imbalance and hemodynamically instability requiring vasopressor support. Discussions were held for re-induction with CLAG (cladribine 5mg/m2, and cytarabine 2gm/m2) vs best supportive care. Patient decided to pursue comfort care and passed away peacefully. The uniqueness of this case is the myeloid sarcoma of testes as initial presentation with normal bone marrow. Misdiagnosis is not uncommon and can delay the appropriate treatment. Extra medullary involvement from leukemia is very aggressive and needs high suspicious and prompt treatment. Systemic chemotherapy using AML-like regimens should be commenced early, even in non leukemic disease. Allogeneic hematopoietic stem cell transplantation has demonstrated promising results, particularly in patients who achieved complete remission with AML-induction protocols, and recent advances in genetic profiling may enable the development of novel targeted therapies. Prospective multicenter controlled trials are required to further refine management decisions and investigate the role of novel targeted therapies. Disclosures No relevant conflicts of interest to declare.

Metastatic plasma cell leukemia to the skin: a case report with review of the literature

Plasma cell leukemia (PCL) is a rare variant of leukemia with an aggressive clinical course and a poor prognosis. The cutaneous involvement in PCL is very rare either at clinical presentation of leukemia, namely “leukemia cutis”, or in the metastatic PCL to the skin. We present a case of eruptive multiple cutaneous nodules in a 56-year-old man with metastatic PCL. Histologically, a diffuse dermal and subcutaneous infiltration of ovoid cells with amphophilic cytoplasm and eccentrically located nucleus consistent with plasmacytoid morphology was observed. Neoplastic cells showed strong immunoexpression for CD138 and CD38 consistent with plasma cells phenotype, and loss of expression of CD56. Kappa light chain restriction similar to the phenotype of his PCL was demonstrated. We suggest that the evaluation of new skin lesions in leukemic patients should include a histopathologic examination to establish the diagnosis as soon as possible and a correct management of the disease.

Molecular findings in bone marrow samples of myeloid sarcoma

Introduction/Objective Myeloid sarcoma is a rare extramedullary manifestation of acute myeloid leukemia. There are very few studies regarding molecular findings in myeloid sarcoma or their associated myeloid leukemia Methods/Case Report We evaluated cases of myeloid sarcoma with concurrent or prior bone marrow studies diagnosed as acute myeloid leukemia, from 2014 to 2021. We searched our Anatomic pathology information system for the terms ‘myeloid sarcoma’ or ‘leukemia cutis’. Out of 58 cases of myeloid sarcoma, ten had next generation sequencing studies (FoundationOne Heme) performed on bone marrow aspirate. Results-There were 7 male and 3 female patients. Age range was from 1-79 yrs. Myeloid sarcoma involved the skin (n=7) or soft tissue (n=3). Most common mutated genes were KMT2A/MLL (n=4, all translocations/fusions) followed by AXL1 (n=3), TP53 (n=3), NRAS (n=2), TET2 (n=2) and CEPBA (n=2). KMT2A fusion partners were MLLT1/ENL (n=1), MLLT3 (n=1), and MLLT10/AF10 (n=2). In all except for one case that harbored KMT2A/MLL fusions, karyotype also showed translocation of KMT2A. Only one case had both an AXL stop codon and a KMT2A translocation, otherwise AXL1/CEBPA mutated cases and KMT2A/MLL mutated cases were mutually exclusive. Other mutated genes were PHF6, BRCA2, DNMT3A, NPM1, RAD21, CBL, KMD6A, and NF1; each found in one case. Results (if a Case Study enter NA) Our result support the notion of higher risk of myeloid sarcoma in KMT2A and TP53 mutated AMLs. Except for absence of spliceosomes mutation, the incidence of mutated genes and functional categories in our series is concordance with two previously published studies. Conclusion Our result support the notion of higher risk of myeloid sarcoma in KMT2A and TP53 mutated AMLs. Except for absence of spliceosomes mutation, the incidence of mutated genes and functional categories in our series is concordance with two previously published studies.

What to Look Out for in a Newborn with Multiple Papulonodular Skin Lesions at Birth

Multiple papulonodular skin lesions at birth can indicate the presence of various benign and malignant disorders. Although the lesions’ clinical aspect (color and consistency, in particular) may steer the clinician towards one disorder or another (infantile myofibromatosis, xanthogranuloma, or metastatic neuroblastoma), the diagnosis can only be confirmed by the histopathologic assessment of a biopsy. In neonates, a rapid but accurate diagnosis is critical because skin lesions may be the first manifestation of a malignant disorder like leukemia cutis or metastatic neuroblastoma. Here, we review the various disorders that may manifest themselves as multiple skin lesions at birth.