Myeloid/Lymphoid Neoplasm with FGFR1 Rearrangement Presenting with Polycythemia Vera and T-cell Acute Lymphoblastic Leukemia.

Myeloid/lymphoid neoplasm with fibroblast growth factor 1 rearrangements (MLN-FGFR1) represents a rare group of hematologic neoplasms, with approximately 100 cases reported to date. A 69-year-old woman with a history of polycythemia and leukocytosis, with negative molecular testing for JAK2, CALR, and MPL, presented with diffuse adenopathy. A lymph node (LN) biopsy revealed effacement by T-lymphoblasts, consistent with T-cell acute lymphoblastic lymphoma (T-ALL). A staging bone marrow (BM) biopsy demonstrated trilineage hyperplasia, which, taken together with the patient's elevated hemoglobin and low serum erythropoietin level, fulfilled diagnostic criteria for polycythemia vera. Karyotype and fluorescence in situ hybridization on both the BM and LN demonstrated a FGFR1 rearrangement due to t(8;13), consistent with MLN-FGFR1. Whole genome sequencing on the LN additionally identified a pathogenic frameshift mutation of ASXL1 NC_000020.11:g32434646dup NM_015338.6(ASXL1):c.1934dup p.(Gly646Trpfs) predicted to result in loss of protein function, a finding also observed in 8.1% of BM reads. Both the BM and LN harbored missense variants in HDAC4 NM_001378414.1(HDAC4):c.[2763G>A]; [2763=] p.(Met921Ile) and CHEK2 NM_007194.4(CHEK2):c.[538C>T];[538=] p.(Arg180Cys), with an unknown significance. Despite initial response to Mini-CVD + venetoclax, the patient subsequently experienced rapid clinical deterioration and death. We report the second case of MLN-FGFR1 with an ASXL1 mutation and the first case with HDAC4 and CHEK2 variants.

Perforating Calcinosis Cutis as a Complication of Intraosseous Fluid Infusion in the Setting of a Near-Drowning Event.

Iatrogenic calcinosis cutis represents a subset of calcinosis cutis resulting secondary to treatments or procedures. We present the first report of calcinosis cutis resulting from the intraosseous infusion and one of a few cases with associated transepidermal elimination. A previously healthy 2-year-old female presented with a new-onset unilateral shin rash 1 week following hospitalization for a near-drowning event. A dermatologic exam revealed multiple small, tender, firm, chalky-white papules with surrounding erythema, in addition to two erythematous macules superior and medial to the papular lesions, corresponding to prior intraosseous access sites. The rash persisted despite trials of topical mupirocin and acyclovir cream, prompting a referral to a dermatologist. An excisional biopsy was performed, revealing circumscribed dermal deposits of acellular basophilic material connected to the overlying epidermis through an invaginated keratin plug. A von Kossa silver stain highlighted the deposits, confirming the diagnosis of perforating calcinosis cutis. The lesions did not recur following the excisional biopsy. Iatrogenic calcinosis cutis may be seen as a complication of the infusion of calcium-containing fluids via intraosseous access, in addition to the more commonly observed peripheral intravenous access. Awareness of this disorder is important in order to distinguish it from an infectious mimic and guide the selection of therapy.

Methylated DNA markers for plasma detection of ovarian cancer: Discovery, validation, and clinical feasibility.

OBJECTIVE: Aberrant DNA methylation is an early event in carcinogenesis which could be leveraged to detect ovarian cancer (OC) in plasma. METHODS: DNA from frozen OC tissues, benign fallopian tube epithelium (FTE), and buffy coats from cancer-free women underwent reduced representation bisulfite sequencing (RRBS) to identify OC MDMs. Candidate MDM selection was based on receiver operating characteristic (ROC) discrimination, methylation fold change, and low background methylation among controls. Blinded biological validation was performed using methylated specific PCR on DNA extracted from independent OC and FTE FFPE tissues. MDMs were tested using Target Enrichment Long-probe Quantitative Amplified Signal (TELQAS) assays in pre-treatment plasma from women newly diagnosed with OC and population-sampled healthy women. A random forest modeling analysis was performed to generate predictive probability of disease; results were 500-fold in silico cross-validated. RESULTS: Thirty-three MDMs showed marked methylation fold changes (10 to >1000) across all OC subtypes vs FTE. Eleven MDMs (GPRIN1, CDO1, SRC, SIM2, AGRN, FAIM2, CELF2, RIPPLY3, GYPC, CAPN2, BCAT1) were tested on plasma from 91 women with OC (73 (80%) high-grade serous (HGS)) and 91 without OC; the cross-validated 11-MDM panel highly discriminated OC from controls (96% (95% CI, 89-99%) specificity; 79% (69-87%) sensitivity, and AUC 0.91 (0.86-0.96)). Among the 5 stage I/II HGS OCs included, all were correctly identified. CONCLUSIONS: Whole methylome sequencing, stringent filtering criteria, and biological validation yielded candidate MDMs for OC that performed with high sensitivity and specificity in plasma. Larger plasma-based OC MDM studies, including testing of pre-diagnostic specimens, are warranted.

Dowling-Degos Disease Presenting With Associated Epidermal Inclusion Cysts: A Case Report and Review of the Literature.

ABSTRACT: Dowling-Degos Disease (DDD) is a rare and disfiguring autosomal dominant genodermatosis characterized by reticulate hyperpigmented macules or follicular comedone-like papules in the intertriginous areas that typically presents in the third or fourth decade of life. It is a progressive disease that is often treatment-resistant. Although its association with hidradenitis suppurativa has been well described, DDD has also been less commonly reported in conjunction with other dermatologic diseases with unknown etiologic associations. Herein, we present a case of DDD with associated epidermal inclusion cysts and conduct a literature review of dermatologic conditions reported in association with DDD.

Rhabdomyomatous mesenchymal hamartoma presenting as a chin nodule in a 15-year-old male.

Rhabdomyomatous mesenchymal hamartoma (RMH), also known as congenital midline hamartoma and striated muscle hamartoma, is a rare congenital malformation presenting most commonly in midline sites of the head and neck region. Since its first description in 1986, 67 cases have been reported to date. We report a case of RMH presenting as a chin nodule in an otherwise healthy 15-year-old male. The patient presented with a dome-shaped subcutaneous lesion on his chin which had been present since birth, but had grown and was interfering with his ability to shave. He otherwise had no history of congenital anomalies or malformations. Histopathological examination of the excised lesion revealed a haphazard proliferation of striated muscle admixed with adipose tissue and adnexal structures within the dermis and subcutaneous tissue, consistent with a diagnosis of RMH. While the majority of reported cases are of newborns or children under 3 years of age, RMH may not come to clinical attention until later in life. This rare malformation should be included in the differential diagnosis of lesions containing dermal striated muscle and/or adipose tissue, to include nevus lipomatosus superficialis, fibrous hamartoma of infancy, neuromuscular choristoma, fetal rhabdomyoma, and rhabdomyosarcoma.

Clinicopathologic predictors of survival in buccal squamous cell carcinoma.

BACKGROUND: Buccal squamous cell carcinoma (SCC) is a locoregionally aggressive malignancy, representing a small subset of oral cancers in North America. We investigated the prognostic value of several clinicopathologic factors in a cohort of patients diagnosed with buccal SCC. METHODS: Between years 1992 and 2017, 52 patients were diagnosed with conventional buccal SCC. Archival surgical pathology material was retrospectively reviewed for reportable findings according to the latest reporting guidelines published by the College of American Pathologists. Clinical data were obtained through chart review. RESULTS: The majority of patients were of older age, current or past smokers, and without specific gender predilection. Most presented at a clinically advanced stage and were treated with surgery alone, or surgery followed by adjuvant radiotherapy. The tumor recurred in about 40% of patients, and almost half of the patients died from the disease by the end of the follow-up period. The worst pattern of invasion (WPOI) was associated with greater depth of invasion (DOI) (P = .031) and perineural invasion (P < .001). In univariate analyses, older age (P = .004), positive nodal status (P = .047), lymphovascular invasion (P = .012), perineural invasion (P = .05), and WPOI-5 (P = .015) were adverse predictors of 5-year overall survival (OS). In multivariate analysis, older age (P = .011), WPOI-5 (P < .001), and perineural invasion (P = .001) remained statistically significant independent prognosticators of worse 5-year OS. CONCLUSIONS: Older age, WPOI-5, and perineural invasion are significant prognosticators of worse OS. WPOI is associated with DOI, a finding which may have important implications for the pathogenesis and biologic behavior of the disease.

High level MYC amplification in B-cell lymphomas: is it a marker of aggressive disease?

While MYC translocations in B-cell lymphoma (BCL) have been extensively studied, the significance of MYC amplification (MYC amp) is poorly understood. This study characterizes BCL showing MYC amp, defined as uncountable FISH signals. Retrospective analysis of all BCL FISH for MYC aberrations performed at our institution (1/2010-2/2018) identified 44/9715 (0.45%) cases with MYC amp. MYC amp probe signals appeared in a cloud-like distribution (70%) or in a single homogenous-staining-region (30%). In total 59% also had MYC separation by breakapart probe indicating concurrent MYC translocation. The most common morphology was large cell (82%) and diagnosis was diffuse large BCL (DLBCL, 50%). In total 88% were germinal center B-cell-like by Hans algorithm. In total 12/42 (29%) cases were "double-hit" by WHO criteria (DHL/THL) in addition to having MYC amp. The estimated 2-year overall survival (OS) of DLBCL cases with MYC amp was 80%. There was no significant difference in OS between DLBCL and DHL/THL among cases with MYC amp, suggesting a poor prognostic impact of MYC amp. However, when compared to a larger cohort of DLBCL and DHL/THL, MYC amp did not have prognostic significance. In summary, MYC amp in BCL is rare, most commonly occurs in DLBCL, and was not associated with survival in our cohort.

Bone Marrow Biopsy Operator Experience and Impact on Aspirate, Biopsy, and Ancillary Testing Quality.

OBJECTIVE: To assess the relationship between bone marrow (BM) biopsy operator experience and both specimen quality and ancillary testing utilization. PATIENTS AND METHODS: We evaluated all referred and in-house (IH) BM biopsy specimens obtained over a contiguous 6-week period from April 3, 2017, to May 19, 2017. The BM specimens were assessed for the length of interpretable marrow, and aspirates were assessed for the presence of spicules. Subgroup comparisons included IH BM obtained by a trained team of nurses within our institution, patients clinically referred (CR) to our institution with outside-obtained BM specimens, and outside pathologist-referred (PR) consultation cases. Ancillary study usage was compared between the first 100 cases of each group. RESULTS: A total of 1191 BM specimens were analyzed, including 600 IH, 288 CR, and 303 PR cases with biopsies and/or aspirates. The average interpretable biopsy lengths of IH, CR, and PR cases were 16.0 mm, 10.0 mm, and 7.0 mm, respectively (P<.001). World Health Organization-recommended length of 15 mm or more was achieved in 61.4%, 26.6%, and 19.1%, respectively (P<.001). Of the aspirates analyzed among IH, CR, and PR cases, 93%, 71.3%, and 73.5% contained spicules, respectively (P<.001). Use of immunohistochemistry, flow cytometry, karyotype, and fluorescence in situ hybridization was higher in CR and PR cases than in IH cases (all P<.05). The IH, CR, and PR cases used on average 1.5, 2.8, and 4.8 immunohistochemistry stains per case (P<.001). CONCLUSION: Having a dedicated team of BM biopsy operators is likely one factor contributing to improved BM biopsy quality and a reduced need for ancillary testing.