Comparison of flow cytometry and next-generation sequencing in minimal residual disease monitoring of acute myeloid leukemia: One institute's practical clinical experience.

INTRODUCTION: Monitoring patients with acute myeloid leukemia can be implemented through various techniques such as multiparameter flow cytometry, real-time quantitative polymerase chain reaction, and next-generation sequencing. However, there is scarce studies when comparing the data of next-generation sequencing and flow cytometry for monitoring disease progression, particularly how they might supplement one another when used in tandem. METHODS: We investigated 107 patients via retrospective analysis using follow-up MFC and NGS data with a total of 717 MFC and 247 NGS studies to compare these methods in monitoring minimal/measurable residual disease. RESULTS: 197 instances were MFC+ /NGS+ , 3 were MFC- /NGS- , 44 were MFC- /NGS+ , and 3 are MFC+ /NGS- . The majority of the MFC- /NGS+ cases occurred within 6 months during the post-treatment phase (64%). Among 44 MFC- /NGS+ instances, 13 had similar NGS profiles to their original day 0 diagnosis. The remaining cases showed preleukemic clonal hematopoiesis mutations, "likely pathogenic mutations," or "variants of uncertain significance." CONCLUSION: Our findings show that flow cytometry has its advantages with comparable sensitivity in detecting minimal/measurable residual disease. Next-generation sequencing could be used in an increased and more regular capacity in conjunction with flow cytometry to achieve a more comprehensive surveillance of these patients, resulting in improved outcomes.

Update on B-cell lymphoproliferative disorders of the gastrointestinal tract.

The gastrointestinal (GI) tract is home to a significant portion of the immune system, which interacts daily with the antigenic milieu of its contents. Therefore, the presence of white blood cells within the walls of the GI tract upon histologic examination is a familiar sight on GI biopsies-both in health and disease. The GI tract is the most common site of extranodal lymphomas, most of which are B-cell neoplasms. Here, we review common and uncommon B-cell neoplasms of the GI tract - extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), mantle cell lymphoma, duodenal-type follicular lymphoma, diffuse large B-cell lymphoma, plasmablastic lymphoma, EBV-positive mucocutaneous ulcer, and post-transplant lymphoproliferative disorders - with special focus on literature published during the past five years. Along with the other articles in this edition of Seminars in Diagnostic Pathology, it is the authors' hope that this review proves to be a useful resource in the workup of the array of hematopoietic processes that can involve the GI tract.

Cervical Papanicolaou tests in the female-to-male transgender population: should the adequacy criteria be revised in this population? An Institutional Experience.

INTRODUCTION: It is recommended that female-to-male (FTM) transgender patients with a cervix follow the same cervical cancer screening guidelines as cisgender women. This study analyzes Papanicolaou tests, HPV results, and follow-up histology in FTM patients, and compares those results to other atrophic populations at our institution. MATERIALS AND METHODS: A cohort of FTM patients receiving androgen therapy was identified through our institution's translational research database. We collected data on Papanicolaou tests, human papillomavirus (HPV) results, follow-up surgical procedures, and duration of androgen therapy. ThinPrep slides were reviewed for cellularity and cytomorphology. The results of these tests were compared with those of an atrophic control group consisting of postpartum and postmenopausal cisgender women. RESULTS: We identified 71 FTM patients with 77 Papanicolaou tests collected over 6 years. Papanicolaou interpretations included: negative for intraepithelial lesion (69%), atypical cells of undermined significance (5%), low grade squamous intraepithelial lesion (1%), atypical glandular cells (1%), and unsatisfactory due to inadequate cellularity (23%). Five of 27 (18.5%) HPV tests were positive. Follow-up surgical specimens did not identify high-grade lesions. Unsatisfactory rates among FTM patients differed significantly from the atrophic group (P < 0.05), while epithelial abnormality rates and HPV positivity did not (P > 0.05). Most FTM Papanicolaou tests reviewed showed features of atrophy. CONCLUSIONS: FTM patients receiving androgen have high Papanicolaou test unsatisfactory rates secondary to atrophy. Epithelial abnormality and HPV rates do not differ significantly from atrophic cisgender patients. Lowering the cellularity threshold for this population to 2000 like that of other atrophic groups should be considered.

Triaging of pleural effusion cytology specimens for ancillary flow cytometric analysis.

INTRODUCTION: There are no established criteria in selecting pleural effusion (PE) specimens for flow cytometric analysis (FCA). FCA on effusion specimens may be ordered by a clinician or a cytopathologist. In an effort to improve lab test utilization, this retrospective study aims to identify characteristics of PE specimens on which the addition of FCA has high diagnostic yield. MATERIALS AND METHODS: We identified consecutive cases of PE cytology specimens on which FCA was performed over a 5-year period (2014-2019). Patient demographic data and history, FCA diagnosis, cytologic diagnosis, cellular quantity and composition, and peripheral blood cell counts were collected. Chi-square, Mann-Whitney U, and t tests were used when appropriate with a significance level of P < 0.05. RESULTS: We identified 164 FCA cases corresponding to 142 patients (age: 19-90 years; male:female 2:1). The majority of cases had no abnormality by cytologic examination, whereas others were obviously malignant due to non-hematologic malignancy. Most (119 of 164, 73%) had negative immunophenotypic studies by FCA. Forty-five of 164 (27%) FCA cases were positive for a monoclonal myeloid or lymphoid population. Clinicopathologic features associated with positive FCA results included a history of hematologic malignancy, peripheral blood lymphocytes of ≥20%, the presence of a monomorphic lymphoid population, large atypical cells, and mitoses. CONCLUSIONS: This study identifies features that are associated with positive FCA in PE cytology specimens. Using these features by cytopathologists to order FCA on PE specimens as a reflex test would significantly reduce unnecessary testing and improve FCA utilization.

Perianal Histoplasmosis Presenting as a Mass Suspicious for Malignancy: A Case Report with Review of Gastrointestinal Manifestations of Histoplasmosis.

BACKGROUND Disseminated histoplasmosis, a disease that can present years after exposure to the causative organism, may manifest in many diverse ways. Although the gastrointestinal tract is involved in most cases, the initial presentation occurring along the gastrointestinal tract, including the colon and rectum, is infrequent. CASE REPORT This case report describes a 66-year-old male patient who presented with an indurated painful perianal lesion that appeared highly suspicious for malignancy on imaging. The patient had no known history of well-established immunocompromised state except for a short course of prednisolone for chronic obstructive pulmonary disease management. A biopsy of the mass was performed, showing chronic inflammation with clusters of epithelioid histiocytes containing characteristic, PAS-fungus stain-positive, intracellular yeast forms consistent with histoplasmosis. There was no evidence of malignancy. A subsequent work-up revealed perihilar nodularity on chest X-ray suggestive of calcified granuloma, a positive Histoplasma Capsulatum Antigen test result, and mildly decreased CD4: CD8 ratio of unknown significance. HIV testing was negative. Treatment with itraconazole and terbinafine was initiated, and at 5-months follow-up, the patient reported significant improvement in signs and symptoms, with undetectable Histoplasma antigen on repeat testing. CONCLUSIONS This case represents an extremely rare presentation of histoplasmosis infection, and highlights the fact that presenting symptoms of histoplasmosis can be vague and may mimic other disease processes, including neoplasia. Biopsy of the lesion with PAS staining and serologic testing is critical in establishing the correct diagnosis.