This issue of the American Journal of Surgical Pathology: Reports and Reviews is centered around challenging diagnostic issues in various leukemic entities, as well as several lymphomas, with an emphasis on advances in molecular testing. Hematopathology has always been at the leading edge of the oncoming revolution in molecular diagnostics, and this is particularly true with regard to myeloid neoplasms, wherein molecular characteristics are invaluable in both categorization and prognostication. Pathologists are routinely asked to incorporate genetic findings into diagnostic reports and interpret results within the context of the whole patient—these skills require a solid understanding of molecular testing methods and are best done in a multidisciplinary setting. In this journal issue, we discuss a variety of leukemias and lymphomas, with an eye toward interesting/challenging diagnostic issues as well as novel genetic findings.
First, Barron et al discuss a myeloid sarcoma, presenting in a patient with a heterogeneous genetic syndrome not known to be associated with risk of malignancy, although with genetic changes that have been found in acute myeloid leukemias. Their report poses interesting questions about whether common mutations in myeloid leukemias fit the usual categorization when found in the clinical context of a genetic syndrome, as well as whether a potential germline predisposition should be considered in patients with a previously unassociated congenital syndrome.
Next, Nageshwar et al continue the discussion of myeloid neoplasms with a genetic predisposition, with a description of a young patient with an initial presentation suspicious for this condition, followed by transformation to chronic myelomonocytic leukemia and then acute myeloid leukemia. The presence of short telomeres and a TERT mutation raises the possibility of a potential novel association between chronic myelomonocytic leukemia and short telomeres, illustrates the range of myeloid neoplasia possible in telomere biology disorders, and sheds light on the increasingly recognized challenging diagnostic scenario of clinically silent or phenotypically heterogeneous genetic disorders presenting with bone marrow failure and/or myelodysplasia.
The discussion of molecular testing in myeloid leukemia is continued in Kroloff and colleagues' report, detailing its invaluable use in a posttransplant setting for monitoring chimerism and clonal evolution. Their description provides a practical example illustrating the need for methodical interpretation of next-generation sequencing, as well as its role in bone marrow engraftment analysis.
Additionally, Hittman et al present a myeloid neoplasm with features of a myelodysplastic/myeloproliferative overlap syndrome, with discordant hypocellularity and thrombocytosis, eluding definitive subclassification as a myelodysplastic syndrome versus myelodysplastic/myeloproliferative neoplasm. The additional presence of an SF3B1 mutation highlights the challenges in subclassification and complex underlying genetic landscape seen in myeloid neoplasia.
In a change of pace, Su et al describe a case of granulomatous slack skin T-cell lymphoma, manifesting as ulcerative and gangrenous lesions, with a rapidly progressive clinical course. Lesions such as these illustrate the wide clinical variability within cutaneous T-cell lymphomas and significant histologic overlap between entities. Sukhanova et al present a high-grade B-cell lymphoma with a focal copy number gain of the MYC locus caused by a chromothripsis event, not detected by conventional fluorescence in situ hybridization despite strong MYC immunohistochemical expression; this unique cytogenetic finding suggests chromothripsis as another mechanism for the activation of MYC in aggressive non-Hodgkin lymphomas and underscores the need for microarray testing in select cases. Finally, Liu et al describe 2 rare cases of hairy cell leukemia with rare immunophenotypes, Suarez-Solis et al report a unique case of myeloid sarcoma, and Murshed et al describe a highly unusual presentation of a hairy cell leukemia, all presenting potential diagnostic pitfalls.
Hematopathology requires the integration of results from multidisciplinary techniques in order to arrive at the best possible diagnosis. Our issue discusses examples of this integration in myeloid neoplasms, lymphomas, and a few other hematopathologic entities, with a focus on diagnostically challenging cases, newly revised or emerging entities within the World Health Organization classification, and the role and impact of genetic testing. We hope that the readers find the issue both useful and interesting.