Rapid adoption of next generation sequencing (NGS) in genomic medicine has been driven by low cost, high throughput sequencing and rapid advances in our understanding of the genetic bases of human diseases. Today, the NGS method has dominated sequencing space in genomic research, and quickly entered clinical practice. Because unique features of NGS perfectly meet the clinical reality (need to do more with less), the NGS technology is becoming a driving force to realize the dream of precision medicine. This article describes the strengths of NGS, NGS panels used in precision medicine, current applications of NGS in cytology, and its challenges and future directions for routine clinical use.

Peripheral T-cell lymphoma (PTCL) may assume a variety of histologic and cytologic appearances. We describe eight cases of PTCL morphologically simulating marginal zone B-cell lymphoma. We reviewed PTCL cases diagnosed in our institution between 1990 and 2000 and selected eight cases for study based on the following criteria: small-cell morphology with abundant, clear cytoplasm and either marginal zone involvement by the neoplastic infiltrate in lymph node biopsies or lymphoepithelial lesions in extranodal biopsies. Histologic features and ancillary studies were reviewed. Patients included six women and two men with a median age of 53 years (range, 35 to 74 years). Six patients were diagnosed with primary nodal PTCL, and two presented with primary extranodal disease. The original diagnosis was PTCL in only four cases; three cases were diagnosed as atypical lymphoid infiltrate, and one case as benign lymphoepithelial lesion. Lymph node biopsies revealed partial effacement of the architecture with residual follicles surrounded by the neoplastic small cells. Extranodal sites included hard palate, tongue, tonsil, and submandibular glands; all but one case demonstrated lymphoepithelial lesions. Monoclonality was demonstrated in six of eight cases (rearrangement of T-cell receptor gene), and three of eight had an aberrant T-cell population by flow cytometry. The differential diagnosis of atypical lymphoid infiltrates with morphologic features of marginal zone B-cell lymphoma should include PTCL. This uncommon morphological mimicry should be recognized, because PTCL is an aggressive disease regardless of morphology and should be treated accordingly.

Langerhans cell histiocytosis (LCH) is a well-known but rare disease that may occur at any age with markedly variable clinical features: self-regressive, localized, multiorgan, aggressive, or fatal outcome. Congenital LCH is rare and often clinically benign. While LCH is characterized by a clonal proliferation of Langerhans cells, its etiology is unknown. Although BRAF V600E mutations were recently identified as a recurrent genetic alteration in LCH cases, the clinical significance of this mutation within the heterogeneous spectrum of LCH is also currently unknown. We studied a cutaneous, benign form of congenital LCH that occurred in a newborn male, without recurrence for 8 years. Histopathologically, the skin lesion excised after birth showed the typical cytologic and immunophenotypic features of LCH. Sequencing analysis of Exon 15 of the BRAF gene revealed the V600D mutation, with an allelic abundance of 25-30%, corresponding to the LCH cells being hemizygous for the mutant allele. BRAF V600E-specific polymerase chain reaction was negative. Our report is the first to identify the rare, variant BRAF V600D mutation in LCH, and provides support for constitutively activated BRAF oncogene-induced cell senescence as a mechanism of regression in congenital, benign LCH. Further, our clinicopathologic findings provide proof for the first time that the V600D mutation can also occur in the absence of ultraviolet light, and can occur in a clinically benign proliferation, similar to the V600E mutation. Additional clinicopathologic studies in larger numbers of LCH patients may be valuable to ascertain the pathophysiologic role of BRAF mutations in LCH.

Acute myeloid leukemia (AML) is a genetically heterogeneous myeloid malignancy that occurs more commonly in adults, and has an increasing incidence, most likely due to increasing age. Precise diagnostic classification of AML requires clinical and pathologic information, the latter including morphologic, immunophenotypic, cytogenetic and molecular genetic analysis. Risk stratification in AML requires cytogenetics evaluation as the most important predictor, with genetic mutations providing additional necessary information. AML with normal cytogenetics comprises about 40%-50% of all AML, and has been intensively investigated. The currently used 2008 World Health Organization classification of hematopoietic neoplasms has been proposed to be updated in 2016, also to include an update on the classification of AML, due to the continuously increasing application of genomic techniques that have led to major advances in our knowledge of the pathogenesis of AML. The purpose of this review is to describe some of these recent major advances in the diagnostic classification and risk stratification of AML.

Extranodal NK/T-cell lymphoma, nasal type, is a rare type of non-Hodgkin lymphoma that is most common in Asia and is driven by Epstein-Barr virus infection. These tumors usually arise in the nasal region; in rare cases they can involve extranasal sites, most often skin, with involvement of the breast being rare. Lymphomas arising adjacent to breast implants are rare, and most cases reported to date have been anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma. Here we report a 41-year-old white woman with bilateral saline breast implants placed for cosmetic reasons who almost 9 years later developed painful swelling at the right-breast implant site. Excisional biopsy revealed lymphoma composed of monomorphic large cells associated with necrosis and angioinvasion. Immunohistochemical analysis showed an aberrant, NK/T-cell immunophenotype with the lymphoma cells being CD2+, CD3+, CD56+, partial CD30+, granzyme B, TIA-1+, CD4+, CD5+, CD7+, and CD8+. In situ hybridization analysis showed Epstein-Barr virus-encoded RNA within the neoplastic cells. Polymerase chain reaction analysis showed monoclonal T-cell receptor-γ chain gene rearrangement. These findings support the diagnosis of extranodal NK/T-cell lymphoma, nasal type. On the basis of our review of the literature, this case is unique. In addition, we believe this case is important to report, because it expands the spectrum of T-cell lymphomas that can be associated with breast implants and may be a forerunner of additional cases to follow.