Chronic lymphocytic leukemia with a FGFR3 translocation: case report and literature review of an uncommon cytogenetic event.

The t(4;14) (p16; q32) with fusion of the IGH (immunoglobulin heavy chain) and FGFR3 (fibroblast growth factor receptor 3) genes are rarely present in patients with chronic lymphocytic leukemia (CLL), with only two previously reported cases. We herein describe a unique case of CLL with the occurrence of a t(4;14) (p16;q32), trisomy 12, and deletion of 11q13-q23 in the same clonal cells. In contrast to myeloma, in which FGFR3 translocations are a common early cytogenetic hit, FGFR3 rearrangement in CLL appears to occur later in the disease course.

CD4-positive T-cell recruitment in primary-provoked localized vulvodynia: potential insights into disease triggers.

OBJECTIVE: To better understand the potential disease triggers of neurogenic inflammation in provoked localized vulvodynia (PLV), our objective was to determine whether the types of infiltrating lymphocytes were different in vestibular biopsies from women with primary PLV, secondary PLV, and unaffected controls. METHODS: Secondary retrospective analysis of archived vestibular biopsies from a series of adult premenopausal women with primary PLV (n = 10), secondary PLV (n = 10), and unaffected controls (n = 4) was performed. All study patients had severe entry dyspareunia for more than 1 year. Subjects were excluded if pregnant, or they had a known infection, or history of generalized vulvodynia. Biopsies were performed during the midfollicular phase. Lymphocyte subtypes were highlighted in histologic sections using antibodies against CD3, CD4, and CD8 and scored as the mean number of T-cell subtypes per high-power field. Flow cytometry was also used to test fresh biopsies from a de novo prospective series of primary PLV (n = 4) and unaffected controls (n = 2). RESULTS: Unaffected control biopsies showed more CD8-positive than CD4-positive T cells, similar to previous reports of the gynecologic tract. In contrast, biopsies from women with primary PLV showed significantly more CD4-positive T cells than those from women with secondary PLV and unaffected controls (p = .003). This observation was further supported by flow cytometry. CONCLUSIONS: CD4-positive T cells are more numerous in vestibular biopsies from premenopausal women with primary PLV. This may be important because subtypes of CD4-positive T cells are specifically recruited by infectious, allergic, or autoimmune triggers. Future studies distinguishing these subtypes may lead to new insights into this common disease.

Multiplex high-throughput gene mutation analysis in acute myeloid leukemia.

Classification of acute myeloid leukemia increasingly depends on genetic analysis. However, the number of known mutations in acute myeloid leukemia is expanding rapidly. Therefore, we tested a high-throughput screening method for acute myeloid leukemia mutation analysis using a multiplex mass spectrometry-based approach. To our knowledge, this is the first reported application of this approach to genotype leukemias in a clinical setting. One hundred seven acute myeloid leukemia cases were screened for mutations using a panel that covers 344 point mutations across 31 genes known to be associated with leukemia. The analysis was performed by multiplex polymerase chain reaction for mutations in genes of interest followed by primer extension reactions. Products were analyzed on a Sequenom MassARRAY system (San Diego, CA). The multiplex panel yielded mutations in 58% of acute myeloid leukemia cases with normal cytogenetics and 21% of cases with abnormal cytogenetics. Cytogenetics and routine polymerase chain reaction-based screening of NPM1, CEBPA, FLT3-ITD, and KIT was also performed on a subset of cases. When combined with the results of these standard polymerase chain reaction-based tests, the mutation frequency reached 78% in cases with normal cytogenetics. Of these, 42% harbored multiple mutations primarily involving NPM1 with NRAS, KRAS, CEBPA, PTPN11, IDH1, or FLT3. In contrast, cases with abnormal cytogenetics rarely harbored more than 1 mutation (1.5%), suggesting different underlying biology. This study demonstrates the feasibility and utility of broad-based mutation profiling of acute myeloid leukemia in a clinical setting. This approach will be helpful in defining prognostic subgroups of acute myeloid leukemia and contribute to the selection of patients for enrollment into trials with novel inhibitors.

Association of JAK2 mutation status and cytogenetic abnormalities in myeloproliferative neoplasms and myelodysplastic/myeloproliferative neoplasms.

Myeloproliferative neoplasms and myelodysplastic/myeloproliferative neoplasms are heterogeneous disorders. JAK2 mutation testing and karyotyping are routinely used for diagnosis but have not been incorporated into risk stratification in Philadelphia chromosome-negative myeloproliferative neoplasms. This study correlated cytogenetic abnormalities with disease stage and JAK2 status. A total of 179 cases were analyzed for the JAK2 mutation. Among them, cytogenetic data were available for 97 cases-45 of 106 JAK2+ and 52 of 73 JAK2-. The JAK2+ group showed a higher frequency of cytogenetic anomalies than the JAK2- group (23/45 [51%] vs 14/52 [27%]). Chromosome 9, chromosome 7, and 20q- were recurrent abnormalities in the JAK2+ group, whereas 13q- and trisomy 21 were common in the JAK2- group. In the JAK2+ group, chromosome 7 and complex cytogenetic abnormalities were associated with excess blasts/blastic transformation (P < .05), whereas no cases with 20q- underwent blastic transformation. Our results suggest that incorporation of JAK2 mutation testing and karyotyping allows for monitoring of disease progression with prognostic and therapeutic implications.

Diagnostic pitfalls in syringocystadenocarcinoma papilliferum: case report and review of the literature.

We report the first case, to our knowledge, of syringocystadenocarcinoma papilliferum with p63-verified squamous differentiation and extensive dermal invasion accompanying in situ components. An 86-year-old woman presented with a neoplasm on the neck, and the intralesional heterogeneity typical of these neoplasms led to an initial diagnosis on needle biopsy favoring squamous cell carcinoma. Excision illustrated diverse morphology, raising a broad differential diagnosis, including more common extracutaneous malignancies, such as breast, gastrointestinal, and ovarian primary tumors. Fortuitous sectioning revealed a focal connection to the skin surface with evidence of apocrine differentiation allowing final diagnosis as syringocystadenocarcinoma papilliferum. Our literature review shows the histologic and immunohistochemical features of syringocystadenocarcinoma papilliferum are not well defined outside of their clear morphologic overlap with syringocystadenoma papilliferum. We describe our findings and diagnostic pitfalls to help pathologists encountering this unusual apocrine neoplasm.

Acute graft-versus-host disease of the heart.

Graft-versus-host disease (GVHD) is a frequent cause of morbidity and mortality after bone marrow transplantation. Acute GVHD most commonly involves the skin, gastrointestinal tract, and liver. Involvement of other organ systems is rare and remains controversial. We report a patient with GVHD who suffered a fatal ventricular arrhythmia shortly after bone marrow transplantation. Autopsy of the heart showed lymphocyte infiltration. Investigations for cardiotrophic viruses were negative, and chimerism analysis of the heart showed both donor and recipient DNA. We conclude that the cause of death was possibly graft-versus-host disease of the heart. A review of the literature revealed a total of 14 cases of possible cardiac GVHD. All but one of the reported cases have occurred in pediatric patients and six of those patients died, suggesting that this may be a rare but frequently fatal complication of pediatric allogeneic stem cell transplant.