A case of AML with complex karyotype and chromosomal rearrangement of KMT2A.

This is a case of an elderly patient diagnosed with acute myeloid leukemia (AML). While morphological findings, including numerous long, slender, cigar-shaped Auer rods, suggested AML with t(8;21), cytogenetic and FISH analysis revealed abnormalities in chromosome 11 and the KMT2A (MLL) gene. The patient also exhibited double minutes, typically seen in AML and linked to a complex karyotype and poor prognosis. Correlating morphological findings with molecular genetics and cytogenetics is crucial for accurate diagnosis and treatment.

A Case of Acute Myeloid Leukemia Mimicking Blastic Plasmacytoid Dendritic Cell Neoplasm: Utility of the Proposed Upcoming WHO-5 Diagnostic Criteria.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive hematologic malignancy which is associated with a distinctive morphologic appearance. However, the morphology is not specific, and diagnostic characterization requires integration of immunophenotypic and genetic testing. We herein report a case of a 35-year-old female patient who presented with worsening cytopenia. A bone marrow aspirate identified medium-sized blastic cells with perinuclear microvacuoles ("pearl neckless"). Occasional blasts demonstrated a "hand mirror" appearance. Tandem flow cytometry showed an atypical population of dim CD45 events with expression of CD4, CD56, CD117, CD123, and monocytic markers such as CD64. Fluorescence in situ hybridization (FISH) showed evidence of a KMT2A rearrangement with an unknown partner on chromosome 19. Expression of MPO and muramidase was present. The final diagnosis was acute monocytic leukemia (AMoL). Due to the overlapping features of acute myeloid leukemia and BPDCN, the 5th Edition of the World Health Organization (WHO) Classification of Haematolymphoid Tumours provides new criteria for the diagnosis of BPDCN. Our case highlights the utility of these criteria.

Rapid acanthocytic schistocytosis and fulminant microangiopathic hemolysis as a preterminal event.

Isolated schistocytosis is a hematological emergency. Clinically significant schistocytosis requires 1% red cell fragments in a high power field. These include triangular fragments, crescents, helmet cells, keratocytes, or microspherocytes.

Bone Marrow Involvement by Aggressive B Cell Lymphoma Undetected by Aspirate Immunophenotyping.

Staging for newly diagnosed lymphoma is an essential diagnostic step aimed at not only estimating prognosis but also refining the ensuing therapeutic pathway. Bone marrow is routinely sampled for this reason. Morphological assessment of the bone marrow aspirate and biopsy remains the gold standard approach. Nonetheless, ancillary testing such as aspirate immunophenotyping is also used with the aim to increase sensitivity and add diagnostic utility, e.g., to provide proof of clonality. Both of these techniques are fraught with shortcomings and concordance is often not perfect. Cases of infiltrative lymphoma identified by morphology, and not detected by flow cytometry highlights the dangers of over reliance on aspirate immunophenotyping. Under sampling, disintegration, fibrosis and hemodilution are but some causes of a false negative flow result. Therefore, neither technique is sufficient in isolation. In this submission, a case of such a discrepancy is presented as an introduction for review of literature that highlights this phenomenon.

A Case of Parathyroid Adenocarcinoma and Hyperparathyroidism, When "CRAB" Symptoms Are Not due to a Plasma Cell Myeloma.

A previously well 49-year-old patient presented to our hospital with symptomatic hypercalcaemia complaining of polyuria and polydipsia, as well as abdominal and lower back pain (serum/ionized calcium at 3.66 milli mole/l and 1.90 milli moles/l). At admission, he had a normocytic anemia (Hb, 99 g/L) and acute kidney injury (creatinine at 161 µM). His parathyroid hormone (PTH) levels were at 67.6 pico moles/l. A plain X-ray of the lumbar spine showed the presence of a lytic lesion in the L4 vertebrae. CT and MRI confirmed this to be a destructive lesion. A subsequent pan CT scan showed a 2.8 cm complex nodule in the left lobe of the thyroid posteriorly. Excisional biopsy of the resected mass was associated with an infiltrative cellular parathyroid neoplasm with solid and nested architectural growth pattern admixed with hemorrhage and focal calcifications. The tumor showed lymphovascular and perineural invasion. At the time of workup and despite the absence of a positive SPEP/UPEP, a bone marrow biopsy was requested to rule out multiple myeloma. His normocellular bone marrow biopsy showed marked paratrabecular fibrosis and extensive bony remodelling but no metastatic invasion. The diagnosis of a metastatic parathyroid carcinoma was made. He is subsequently considered for palliative radiotherapy to the primary tumor bed and the lumbar spine. In addition, a role for immunotherapy with ipilimumab and nivolumab in context of clinical trials is envisioned and he is being considered for enrollment.

Chronic lymphocytic leukemia with progressive anemia secondary to development of composite lymphoma.

Deterioration of hematologic parameters in lymphoma patients is often attributed to disease progression, comorbidities, or treatment effects. Second primary malignancies occur at increased frequency in CLL and must also be considered.

Therapy related acute myeloid leukemia with blast cannibalism and cytophagocytosis.

The case of an 83-year old male patient is described. He presented to our hospital with a 2 week history of intermittent syncope and was diagnosed with atrial fibrillation. His CBC showed bicytopenia with anemia and neutropenia in context of a leucoerythroblastic blood film and blastemia. As the patient was previously diagnosed with stage IV diffuse large B cell lymphoma; treated with CHOP-R a bone marrow biopsy was requested to rule out acute leukemia. A cellular bone marrow aspirate showed presence of a myeloblast infiltrate (32.6%; confirmed by flow cytometry). Interestingly blast phagocytosis of terminally differentiated cells along with cannibalism of other blasts was identified. The diagnosis of therapy-related acute myeloid leukemia was reached and a palliative consultation was requested. To our knowledge, this is the first report of blast cytophagocytosis and cannibalism associated with a therapy-related acute myeloid leukemia with a complex karyotype.

A case of bony lytic lesions in a patient with Gaucher disease.

Gaucher disease is a clinically heterogeneous disorder of glucocerebroside metabolism and may present incidentally late in life with unexplained thrombocytopenia, splenomegaly, or bony lesions. Clinicians should be aware that patients with Gaucher disease appear to have an increased risk for developing hematolymphoid malignancies, particularly monoclonal gammopathies and plasma cell myeloma.