Triple-Negative Primary Myelofibrosis: A Bone Marrow Pathology Group Study.

Primary myelofibrosis (PMF) is a clonal myeloproliferative neoplasm driven by canonical gene mutations in JAK2, CALR, or MPL in >80% of the cases. PMF that lacks these canonical alterations is termed triple-negative PMF (TN-PMF). The pathologic and genetic characteristics of TN-PMF compared with those of conventional PMF with canonical driver mutations (DM-PMF) have not been well studied. We aimed to identify clinicopathologic and molecular genetic differences between patients with TN-PMF (n = 56) and DM-PMF (n = 89), all of whom fulfilled the 2016 World Health Organization diagnostic criteria for PMF. Compared with the control group, patients in the TN-PMF group were more likely to have thrombocytopenia and less likely to have organomegaly. The bone marrow in patients with TN-PMF showed fewer granulocytic elements and more frequent dyserythropoiesis. Cytogenetic analysis showed a higher incidence of trisomy 8. Targeted next-generation sequencing revealed a lower frequency of ASXL1 mutations but enrichment of ASXL1/SRSF2 comutations. Our findings demonstrated several clinicopathologic and molecular differences between TN-PMF and DM-PMF. These findings, particularly the observed mutation profile characterized by a higher frequency of ASXL1 and SRSF2 comutation, suggest that at least a subset of TN-PMF may be pathogenetically different from DM-PMF, with potential prognostic implications.

Fine Needle Biopsies of Solid Pancreatic Lesions: Tissue Acquisition Technique and Needle Design Do Not Impact Specimen Adequacy.

BACKGROUND AND AIMS: Data on adequacy of EUS guided biopsies using different tissue acquisition techniques and fine needle aspiration needle designs have been inconclusive. Data on newer fine needle biopsy (FNB) needles are scarce. This study compared the performance of 3 acquisition techniques and 2 fine needle biopsy designs in solid pancreatic lesions. METHODS: Single-center, randomized, pilot clinical trial (Trial registration number NCT03264092). Patients undergoing EUS biopsy of pancreatic lesions were randomized to 1 of 3 acquisition techniques (dry suction, wet suction, slow pull) and 1 of 2 22G FNB needle designs. The primary outcome was specimen cellularity. Secondary outcomes included blood contamination and number of passes needed for diagnosis. RESULTS: A total of 52 (35.3%), 49 (33.3%) and 46 (31.3%) specimens were obtained with slow pull, dry suction and wet suction, respectively. A total of 56 (38%) and 91 (62%) specimens were obtained with each needle, respectively. No difference in cellularity scores was identified by technique (3.28 vs 3.55 vs 2.94; p = 0.081) or needle type (3.45 vs 3.15; p = 0.19). The same was true for blood contamination and diagnostic pass. A diagnosis was reached after 3 passes in 51 patients (93%). Histological diagnosis was possible in 45 specimens (82%). No severe adverse events occurred. CONCLUSIONS: Cellularity of pancreatic specimens obtained with FNB needles via EUS was not influenced by technique and needle design. Three passes were enough to obtain a histological diagnosis in most patients. Larger clinical trials are required to validate the results of this study.

Ethnic and border differences on blood cancer presentation and outcomes: A Texas population-based study.

BACKGROUND: The Texas/Chihuahua (US/Mexico) border is a medically underserved region with many reported barriers for health care access. Although Hispanic ethnicity is associated with health disparities for many different diseases, the population-based estimates of incidence and survival for patients with blood cancer along the border are unknown. The authors hypothesized that Hispanic ethnicity and border proximity is associated with poor blood cancer outcomes. METHODS: Data from the Texas Cancer Registry (1995-2016) were used to investigate the primary exposures of patient ethnicity (Hispanic vs non-Hispanic) and geographic location (border vs non-border). Other confounders and covariates included sex, age, year of diagnosis, rurality, insurance status, poverty indicators, and comorbidities. The Mantel-Haenszel method and Cox regression analyses were used to determine adjusted effects of ethnicity and border proximity on the relative risk (RR) and survival of patients with different blood cancer types. RESULTS: Hispanic patients were diagnosed at a younger age than non-Hispanic patients and presented with increased comorbidities. Whereas non-Hispanics had a higher incidence of developing blood cancer compared with Hispanics overall, Hispanics demonstrated a higher incidence of acute lymphoblastic leukemia (RR, 1.92; 95% CI, 1.79-2.08; P < .001) with worse outcomes. Hispanics from the Texas/Chihuahua border demonstrated a higher incidence of chronic myeloid leukemia (RR, 1.28; 95% CI, 1.07-1.51; P = .02) and acute myeloid leukemia (RR, 1.17; 95% CI, 1.04-1.33; P = .0009) compared with Hispanics living elsewhere in Texas. CONCLUSIONS: Hispanic ethnicity and border proximity were associated with a poor presentation and an adverse prognosis despite the younger age of diagnosis. Future studies should explore differences in disease biology and treatment strategies that could drive these regional disparities.

Myeloid, mast cell, histiocytic and dendritic cell neoplasms and proliferations involving the spleen.

Splenic involvement and consequent splenomegaly are usually seen as part of systemic involvement by myeloid neoplasms as well as mast cell and histiocytic neoplasms. Primary splenic involvement by these neoplasms is rare. Splenectomy is usually not performed for establishing a diagnosis of these entities. However, in rare instances, the pathologist may need to evaluate the spleen secondary to splenic rupture or palliative splenectomy to alleviate symptoms related to splenomegaly. This review article describes the clinicopathologic features of a broad group of myeloid, mastocytic, and histiocytic proliferative and neoplastic disorders.

T-cell neoplasms in the spleen.

Hematopoietic neoplasms involving the spleen are uncommon, but T cell neoplasms involving the spleen are extremely rare. The rarity of splenic involvement by T cell neoplasms has resulted in a limited body of literature describing their splenic characteristics. As a result, our purpose in this review article is to provide and summarize some of the characteristics seen by different T cell neoplasms that may involve the spleen.

Pathology teaching in different undergraduate medical curricula within and outside the United States: a pilot study.

Pathology education is taught using different curricula in the United States (USA) and abroad. We evaluate and compare the hours spent in different forms of pathology teaching such as lectures, team-based learning (TBL), problem-based learning (PBL), and other methods taught in general and systemic pathology amongst different medical schools within the USA and outside the USA. The total number of lecture hours taught in general and systemic pathology combined was greater in outside schools than within the USA (141 h vs 97.8 h, respectively). Three subjects in general pathology and six subjects in systemic pathology had a significantly greater lecture hours in outside medical schools. The greatest difference was the hours spent in labs were longer for both general and systems pathology in schools outside the USA. The overall utilization of PBL in general and systemic pathology teaching combined was much greater outside the USA compared to within the USA (average overall hours PBL - 97.2 outside vs 16.5 in the USA), however, the reverse was observed for using TBL (average overall hours TBL - 59.5 outside vs 84.5 in USA). Average hours used with other methods of teaching was also greater in outside medical schools compared to USA medical schools (80.8 h vs 44 h, respectively). Pathology teaching in both general and systemic pathology has more extensive lecture hours, laboratory hours, PBL, and other methods of teaching pathology in outside medical schools with different curricula than USA medical schools. TBL is utilized more extensively in USA medical schools.

Coccidioidomycosis masquerading as thyroid nodule: a rare diagnostic challenge.

We present a compelling case of disseminated coccidioidomycosis involving the thyroid gland, a remarkably uncommon manifestation of this infection. The gravity of this sporadic disease is underscored by its high mortality rate, primarily because of challenges in timely diagnosis and treatment initiation. Accurate diagnosis hinges upon utilizing various techniques, including the culture of a fine-needle aspirate, biopsy and direct microscopy. However, the medical community is still grappling with the optimal treatment strategy, encompassing considerations such as duration and dosage of medications, which continue to be subjects of intense controversy and ongoing research. This article aims to report an older patient with the incidental diagnosis and management of Coccidioides in the thyroid.

Attack of the Clones: A Patient With Untreated Aplastic Anemia Presenting With Classical Paroxysmal Nocturnal Hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired X-linked, clonal hematopoietic stem cell disease. Patients with PNH may complain of vague symptomatology that contributes to the challenge of its diagnosis. This is especially true in the clinical context of a coinciding hematologic disorder. Aplastic anemia (AA) is an additional immune-mediated illness that results in the destruction of hematopoietic precursors and pancytopenia. The authors encourage screening for PNH clones in patients initially diagnosed with AA, treating underlying hematologic disease to prevent clonal expansion, and further research to investigate the effectiveness of eculizumab in an unusual "classical" PNH secondary to AA with hypercellular bone marrow.

A Rare Case of Herpes Simplex Virus and Cytomegalovirus Dual Infection Inducing Unremitting Ulcerative Colitis.

Ulcerative colitis (UC) is a subtype of inflammatory bowel disease that results in inflammation and ulceration in the lining of the large intestine. Patients with UC are frequently prescribed immunosuppressive medications to treat their symptoms, resulting in an increased risk of reactivation of many latent viruses, including herpes simplex virus (HSV) and cytomegalovirus (CMV). However, it is rare for a patient to present with simultaneous reactivation of both viruses. Here, we document the presentation, hospital course, and clinical findings of a UC patient with HSV and CMV dual infection. We also describe treatment strategies and prophylactic measures for managing a dual infection. This is seen through initiating valganciclovir in the outpatient setting following the diagnosis.

Primary Urethral Malignant Peripheral Neural Sheath Tumor in a 58-Year-Old Female in the Absence of Neurofibromatosis Type 1.

A malignant peripheral neural sheath tumor (MPNST) is a malignant soft tissue neoplasm with cellular origin arising from the outer lining of peripheral nerves. Approximately 10 cases have been identified to date where the lower urinary tract was affected. We discuss the case of a female patient that presented with primary MPNST that arose in the urethral tract in the absence of neurofibromatosis type 1 (NF1) or prior malignancies. This patient presented with pain and acute urinary tract symptoms secondary to urethral obstruction by a protruding vaginal mass. The patient underwent an incomplete initial resection to alleviate symptoms and to obtain a tissue diagnosis. Three months after the first hospitalization, the patient was re-hospitalized due to the recurrence of symptoms and subsequently underwent a complete tumor excision. The initial resection showed a 7.0 x 4.5 x 4.5 cm aggregate of tan-red to gray tumor masses. Microscopic examination showed a spindle cell neoplasm with malignant cytological features (hypercellularity, atypical mitoses, nuclear pleomorphism, and indistinct borders). Tumor cells stained positive for SOX10, S-100 (10% of tumor), with a "mosaic pattern" of H3K27ME3 (50% of tumor nuclei positive). Other lineage-specific and keratin markers stained negative. In the absence of other patient known primaries, the findings were consistent with a primary MPNST of the urinary tract. Residual tumor was identified on MRI scans one month after the follow-up. The completely excised tumor specimen on the second admission showed identical morphology when compared to the first specimen. While MPNSTs typically carry a poor prognosis, knowledge of behavior and prognosis of primary MPNSTs in the bladder is limited, due to the few relative numbers of available case reports. Further research is needed to study the clinical behavior, morphology, immunophenotypes, and genetics of primary MPNSTs arising from the lower urinary tract.

Esophageal Pseudotumor Secondary to Treatment with a Potassium Binder Resin: A Case of Severe Esophagitis Mimicking a Malignancy.

Background. Sodium polystyrene sulfonate is a resin used to treat hyperkalemia. Colonic mucosal injury, intestinal ischemia, necrosis, and perforation have been widely reported in the literature, but few cases have reported upper gastrointestinal injury and identify the endoscopic features. Case Presentation. We describe a case of an 83-year-old male, with no prior esophageal symptoms, who developed dysphagia after being treated with sodium polystyrene sulfonate for hyperkalemia. Endoscopic features consistent with severe esophagitis and a mass in the lower esophagus mimicking a malignancy were found, and pathology confirmed resin-induced esophagitis. Discussion. The identification of basophilic crystals in the epithelium with surrounding inflammation is a hallmark of sodium polystyrene sulfonate-induced mucosal injury. Several direct and indirect mechanisms by which SPS may cause mucosal injury have been identified. Prolonged stasis of crystals in the lumen has the potential of developing erosions and ultimately necrosis. The internalization of these crystals to the underlying intestinal mucosa with the combination of the inflammatory response may give an appearance of a luminal mass that can mimic a malignancy. Recognizing the wide-ranging endoscopic findings of resin-induced mucosal injury in the esophagus is fundamental to consider a potential side effect of sodium polystyrene sulfonate. The use of this resin should be avoided in patients with suspected esophageal motility disorder.

Premalignant Conditions of Bone.

Development of malignancy is a multifactorial process, and there are multitude of conditions of bone that may predispose patients to malignancy. Etiologies of malignancy include benign osseous conditions, genetic predisposition, and extrinsic conditions. New-onset pain or growth in a previously stable lesion is that should concern for malignant change and should prompt a diagnostic workup for malignancy.

Loss of G0/G1 switch gene 2 (G0S2) promotes disease progression and drug resistance in chronic myeloid leukaemia (CML) by disrupting glycerophospholipid metabolism.

Tyrosine kinase inhibitors (TKIs) targeting BCR::ABL1 have turned chronic myeloid leukaemia (CML) from a fatal disease into a manageable condition for most patients. Despite improved survival, targeting drug-resistant leukaemia stem cells (LSCs) remains a challenge for curative CML therapy. Aberrant lipid metabolism can have a large impact on membrane dynamics, cell survival and therapeutic responses in cancer. While ceramide and sphingolipid levels were previously correlated with TKI response in CML, the role of lipid metabolism in TKI resistance is not well understood. We have identified downregulation of a critical regulator of lipid metabolism, G0/G1 switch gene 2 (G0S2), in multiple scenarios of TKI resistance, including (1) BCR::ABL1 kinase-independent TKI resistance, (2) progression of CML from the chronic to the blast phase of the disease, and (3) in CML versus normal myeloid progenitors. Accordingly, CML patients with low G0S2 expression levels had a worse overall survival. G0S2 downregulation in CML was not a result of promoter hypermethylation or BCR::ABL1 kinase activity, but was rather due to transcriptional repression by MYC. Using CML cell lines, patient samples and G0s2 knockout (G0s2-/- ) mice, we demonstrate a tumour suppressor role for G0S2 in CML and TKI resistance. Our data suggest that reduced G0S2 protein expression in CML disrupts glycerophospholipid metabolism, correlating with a block of differentiation that renders CML cells resistant to therapy. Altogether, our data unravel a new role for G0S2 in regulating myeloid differentiation and TKI response in CML, and suggest that restoring G0S2 may have clinical utility.

Primary pancreatic diffuse large B-cell lymphoma, activated B-cell subtype, diagnosed by endoscopic ultrasound-guided fine needle aspiration-A case report and review of the literature.

Although primary pancreatic lymphoma is a rare cause of pancreatic mass, this diagnosis should be considered during work-up. Furthermore, when adequate diagnostic material is available from biopsy, complete workup of the lymphoma, including not only type but also subtype when applicable, should be performed.

Dysphagia as the Presenting Symptom for Inclusion Body Myositis.

Dysphagia can be one of the manifestations of inflammatory myopathies (IMs). In some patients, it can be one of the presenting symptoms or the only symptom. We present a patient with dysphagia and progressive muscle weakness who was eventually diagnosed with inclusion body myositis (IBM). Treatment with oral steroid provided no major improvement in symptoms and thus was eventually stopped. Dysphagia in IMs is associated with complications and poor prognosis. A multidisciplinary approach is needed in its diagnosis and management as this report exemplifies.

Treatment of Primary Mediastinal B-Cell Lymphoma With R-CEOP (Rituximab, Cyclophosphamide, Etoposide, Vincristine, and Prednisone).

Primary mediastinal B-cell lymphoma (PMBCL) is a rare subtype of non-Hodgkin's lymphoma. It typically has an aggressive behavior with potential clinical emergencies including cardiac tamponade, thrombosis of major neck vessels, airway obstruction, and tumor lysis syndrome. In this case report, a 38-year-old Caucasian male presented with shortness of breath, a two-month history of 40-pound weight loss, and a left-sided chest wall mass. CT imaging showed a mediastinal mass, measuring 13 × 14.6 × 8.6 cm3, with invasion and partial occlusion of the brachiocephalic veins and upper superior vena cava causing superior vena cava syndrome, and encasement of multiple coronary artery segments. CT-guided biopsy showed high-grade B-cell lymphoma. Cytology biomarkers were positive for CD20, CD45, and PAX5. A trans-thoracic echocardiogram (TTE) was obtained prior to chemotherapy initiation to establish a baseline for cardiac function, which showed an ejection fraction (EF) of 45-50%, right ventricle volume overload and dilation, and pulmonary hypertension. R-CEOP (rituximab, cyclophosphamide, etoposide, vincristine, and prednisone) chemotherapy regimen was initiated and a follow-up echocardiogram after three cycles, revealed a significant improvement in EF; the patient subsequently received three additional cycles of R-EPOCH. Current regimens in the United States utilize dose-adjusted R-EPOCH and R-CHOP, but they must be used cautiously in patients with compromised cardiac function, due to the cardiotoxic side effects of the chemotherapy agent, doxorubicin. This case illustrates that anthracycline-free regimens should be considered in patients with reduced cardiac function, with this case showing the utilization of an anthracycline-free regimen (R-CEOP) for the first three cycles, followed by a transition to R-EPOCH.

Lenalidomide induced durable remission in a patient with MDS/MPN-with ring sideroblasts and thrombocytosis with associated 5q- syndrome.

We describe a patient with MDS/MPN with ring sideroblasts and thrombocytosis who had deletions of long arm of chromosome 5 (5q-) and chromosome 20 (20q-). Molecular studies showed an exon 9, frame shift mutation in the calreticulin (CALR) gene, and absence of mutations in JAK2, MPL, SETBP1 or SF3B1. Treatment with lenalidomide resulted in durable clinical remission which has lasted 2 years.

Epithelial-Mesenchymal Transition Markers in Breast Cancer and Pathological Responseafter Neoadjuvant Chemotherapy.

The association between pathologic complete response (pCR) following to neoadjuvant chemotherapy (NAC) and the improved survival in breast cancer has been previously reported. The aim of this study was is to explore the expression of several biomarkers described during epithelial-mesenchymal transition (EMT) and the achievement of pCR in different molecular subtypes of breast cancer. We identified archived pathology tissue from patients with breast cancer who received NAC during the year 2014. We performed immunohistochemical analysis of vimentin, nuclear factor κB (NF-κB), epidermal growth factor receptor (EGFR), E-cadherin, estrogen receptor (ER), progesterone receptor, and Her2neu and studied the association between the expression of these markers and pCR. A Fisher exact test for categorical cofactors, an unpaired t test and a nonparametric Wilcoxon test for continuous cofactors were used. The results showed a significant expression of vimentin in triple-negative breast cancer (TNBC; P = .023). An inverse correlation between vimentin and the ER expression (P = .032) was observed. No significant association was noted for vimentin, NF-κB, EGFR, and E-cadherin was associated with pCR. This study suggests that the evaluated EMT related biomarkers are not associated with pCR after NAC chemotherapy in an unselected breast cancer population. Vimentin and NF-κB expressions were associated with TNBC and could be further explored as potential therapeutic targets in this subgroup. A prevalence of vimentin and NF-κB among Hispanic patients with breast cancer warrants further investigation as a possibly contributing to the prevalence of TNBC and adverse prognosis in this population.