Molecular Pathology Laboratory Network

Hypereosinophilia represents a diagnostic challenge. As in the past, one must clinically exclude benign secondary reactive causes such as infection, hypersensitivity, paraneoplastic reaction, pulmonary and autoimmune diseases. If there is persistent, unexplained eosinophilia lasting more than 6 months without attributable cause, one might consider myeloproliferative neoplasms with dominant eosinophilia, chronic eosinophillic leukemia, rare myeloid and lymphoid neoplasms with recurrent genetic abnormalities or the shrinking category of hypereosinophilia syndrome.

The majority of Enteropathy-associated T-cell lymphomas (EATL) are associated with adult onset gluten-sensitive enteropathy with which they have a similar geographic distribution, which are usually CD56- CD103+. A minor subset of EATLs (Type II; monomorphic variant) is not as clearly associated with gluten-sensitive enteropathy. These subsets are typically CD56+ CD8+. Both subtypes are CD4-, and >80% positive for chromosomal gains at chromosome 9q31.3. In the case of Type II EATL, clinical correlation is required to exclude unlikely secondary GI involvement by an unusual CD56+ peripheral T-cell lymphoma, NOS.

A recently published phase 3 clinical trial demonstrates that a novel melanoma therapy targeted to the BRAF V600E gene mutation has significant therapeutic efficacy against BRAF V600E mutated melanomas. The BRAF V600E mutation is present in 30-60% of cutaneous melanomas.

Vemurafenib, a drug with specific inhibitory activity against the BRAF V600E mutated kinase, demonstrates superior overall and progression-free survival compared to dacarbazine in patients with previously untreated, metastatic BRAF V600E mutation-positive melanoma.

Acute panmyelosis with myelofibrosis is rare and typically presents to pathologists with morphologic features resembling a fibrotic stage of primary myelofibrosis or end-stage of myelproliferative neoplasia-NOS, sometimes resembling acute megakaryoblastic leukemia.

However, as in this case, an acute clinical presentation, peripheral smear morphology, and absence of splenomegaly argue against a chronic myelproliferative neoplasm. In this case, diagnosis is further supported by negative testing for JAK2 mutation V617F and BCR-ABL/ t(9;22). The relatively low blast count argues against acute megakaryoblastic leukemia.