Fifth Edition of the World Health Organization Classification of Tumors of the Hematopoietic and Lymphoid Tissues: Mature T-Cell, NK-Cell, and Stroma-Derived Neoplasms of Lymphoid Tissues.

This review focuses on mature T cells, natural killer (NK) cells, and stroma-derived neoplasms in the fifth edition of the World Health Organization classification of hematolymphoid tumors, including changes from the revised fourth edition. Overall, information has expanded, primarily due to advancements in genomic understanding. The updated classification adopts a hierarchical format. The updated classification relies on a multidisciplinary approach, incorporating insights from a diverse group of pathologists, clinicians, and geneticists. Indolent NK-cell lymphoproliferative disorder of the gastrointestinal tract, Epstein-Barr virus-positive nodal T- and NK-cell lymphoma, and several stroma-derived neoplasms of lymphoid tissues have been newly introduced or included. The review also provides guidance on how the fifth edition of the World Health Organization classification of hematolymphoid tumors can be applied in routine clinical practice.

SOX11+ Large B-Cell Neoplasms: Cyclin D1-Negative Blastoid/Pleomorphic Mantle Cell Lymphoma or Large B-Cell Lymphoma?

Large or blastoid B-cell neoplasms that are SOX11+ are a diagnostic dilemma and raise a differential diagnosis of cyclin D1-negative blastoid/pleomorphic mantle cell lymphoma (MCL) versus diffuse large B-cell lymphoma (DLBCL) or blastoid high-grade B-cell lymphoma (HGBL) with aberrant SOX11 expression. Here we report a study cohort of 13 SOX11+ large/blastoid B-cell neoplasms. Fluorescence in situ hybridization analysis was negative for CCND1 rearrangement in all 13 cases; 1 of 8 (12.5%) cases tested showed CCND2 rearrangement and 2 (25%) cases had extracopies of CCND2. Gene expression profiling showed that the study group had a gene expression signature similar to cyclin D1+ blastoid/pleomorphic MCL but different from DLBCL. Principal component analysis revealed that the cohort cases overlapped with cyclin D1+ blastoid/pleomorphic MCL but had minimal overlap with DLBCL. All patients in the cohort had clinicopathologic features similar to those reported for patients with cyclin D1+ MCL. We also performed a survey of SOX11 expression in a group of 85 cases of DLBCL and 24 cases of blastoid HGBL. SOX11 expression showed a 100% specificity and positive predictive value for the diagnosis of MCL. Overall, the results support the conclusion that large or blastoid B-cell neoplasms that are positive for SOX11 are best classified as cyclin D1-negative blastoid/pleomorphic MCL, and not as DLBCL or blastoid HGBL. We also conclude that SOX11 is a specific marker for the diagnosis of MCL, including cyclin D1-negative blastoid/pleomorphic MCL cases and should be performed routinely on blastoid/large B-cell neoplasms to help identify potential cases of cyclin D1-negative blastoid/pleomorphic MCL.

EBV-positive diffuse large B-cell lymphoma, not otherwise specified: 2024 update on the diagnosis, risk-stratification, and management.

DISEASE OVERVIEW: Epstein Barr virus-positive (EBV+) diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) is an aggressive B-cell lymphoma associated with EBV infection included in the WHO classification of lymphoid neoplasms since 2016. Although historically associated to poor prognosis, outcomes seem to have improved in the era of chemoimmunotherapy. DIAGNOSIS: The diagnosis is established through meticulous pathological evaluation. Detection of EBV-encoded RNA (EBER) is the standard diagnostic method. The ICC 2022 specifies EBV+ DLBCL, NOS as occurring when >80% of malignant cells express EBER, whereas the WHO-HAEM5 emphasizes that the majority of tumor cells should be EBER positive without setting a defined threshold. The differential diagnosis includes plasmablastic lymphoma, DLBCL associated with chronic inflammation, primary effusion lymphoma, among others. RISK-STRATIFICATION: The International Prognostic Index (IPI) and the Oyama score can be used for risk-stratification. The Oyama score includes age >70 years and presence of B symptoms. The expression of CD30 and PD-1/PD-L1 are emerging as potential adverse but targetable biomarkers. MANAGEMENT: Patients with EBV+ DLBCL, NOS, should be staged and managed following similar guidelines than patients with EBV-negative DLBCL. EBV+ DLBCL, NOS, however, might have a worse prognosis than EBV-negative DLBCL in the era of chemoimmunotherapy. Therefore, inclusion of patients in clinical trials when available is recommended. There is an opportunity to study and develop targeted therapy in the management of patients with EBV+ DLBCL, NOS.

Optical genome mapping improves the accuracy of classification, risk stratification, and personalized treatment strategies for patients with acute myeloid leukemia.

Cytogenomic characterization is crucial for the classification and risk stratification of acute myeloid leukemia (AML), thereby facilitating therapeutic decision-making. We examined the clinical utility of optical genome mapping (OGM) in 159 AML patients (103 newly diagnosed and 56 refractory/relapsed), all of whom also underwent chromosomal banding analysis (CBA), fluorescence in situ hybridization, and targeted next-generation sequencing. OGM detected nearly all clinically relevant cytogenetic abnormalities that SCG identified with >99% sensitivity, provided the clonal burden was above 20%. OGM identified additional cytogenomic aberrations and/or provided information on fusion genes in 77 (48%) patients, including eight patients with normal karyotypes and four with failed karyotyping. The most common additional alterations identified by OGM included chromoanagenesis (n = 23), KMT2A partial tandem duplication (n = 11), rearrangements involving MECOM (n = 7), NUP98 (n = 2), KMT2A (n = 2), JAK2 (n = 2), and other gene fusions in 17 patients, with 10 showing novel fusion gene partners. OGM also pinpointed fusion genes in 17 (11%) patients where chromosomal rearrangements were concurrently detected by OGM and CBA. Overall, 24 (15%) aberrations were identified exclusively by OGM and had the potential to alter AML classification, risk stratification, and/or clinical trial eligibility. OGM emerges as a powerful tool for identifying fusion genes and detecting subtle or cryptic cytogenomic aberrations that may otherwise remain undetectable by CBA.

The recombinant L-lysine α-oxidase from the fungus Trichoderma harzianum promotes apoptosis and necrosis of leukemia CD34 + hematopoietic cells.

BACKGROUND: In hematologic cancers, including leukemia, cells depend on amino acids for rapid growth. Anti-metabolites that prevent their synthesis or promote their degradation are considered potential cancer treatment agents. Amino acid deprivation triggers proliferation inhibition, autophagy, and programmed cell death. L-lysine, an essential amino acid, is required for tumor growth and has been investigated for its potential as a target for cancer treatment. L-lysine α-oxidase, a flavoenzyme that degrades L-lysine, has been studied for its ability to induce apoptosis and prevent cancer cell proliferation. In this study, we describe the use of L-lysine α-oxidase (LO) from the filamentous fungus Trichoderma harzianum for cancer treatment. RESULTS: The study identified and characterized a novel LO from T. harzianum and demonstrated that the recombinant protein (rLO) has potent and selective cytotoxic effects on leukemic cells by triggering the apoptotic cascade through mitochondrial dysfunction. CONCLUSIONS: The results support future translational studies using the recombinant LO as a potential drug for the treatment of leukemia.

Proteome profiling of enriched membrane-associated proteins unraveled a novel sophorose and cello-oligosaccharide transporter in Trichoderma reesei.

BACKGROUND: Trichoderma reesei is an organism extensively used in the bioethanol industry, owing to its capability to produce enzymes capable of breaking down holocellulose into simple sugars. The uptake of carbohydrates generated from cellulose breakdown is crucial to induce the signaling cascade that triggers cellulase production. However, the sugar transporters involved in this process in T. reesei remain poorly identified and characterized. RESULTS: To address this gap, this study used temporal membrane proteomics analysis to identify five known and nine putative sugar transporters that may be involved in cellulose degradation by T. reesei. Docking analysis pointed out potential ligands for the putative sugar transporter Tr44175. Further functional validation of this transporter was carried out in Saccharomyces cerevisiae. The results showed that Tr44175 transports a variety of sugar molecules, including cellobiose, cellotriose, cellotetraose, and sophorose. CONCLUSION: This study has unveiled a transporter Tr44175 capable of transporting cellobiose, cellotriose, cellotetraose, and sophorose. Our study represents the first inventory of T. reesei sugar transportome once exposed to cellulose, offering promising potential targets for strain engineering in the context of bioethanol production.

Tympanostomy Tube Otorrhea: Microbiological Differences Between Children with and Without Cleft Palate.

OBJECTIVE: To characterize and compare microbiological profiles in tympanostomy tube otorrhea for children with and without cleft palate. DESIGN: Retrospective cohort study. SETTING: Pediatric otolaryngology and multidisciplinary cleft/craniofacial clinic at a single tertiary care center. PATIENTS: Children with and without cleft palate <18 years of age who underwent tympanostomy tube placement between 2017-2021. MAIN OUTCOME MEASURES: Otopathogen profiles and antibiotic resistance patterns in ear culture specimens obtained in children presenting for treatment of recalcitrant post-tympanostomy tube otorrhea. RESULTS: Of the 886 children with tympanostomy tubes placed between 2017-2021, 345 (38.9%) had clinically significant otorrhea defined as requiring at least one otolaryngology visit for treatment. Children with cleft palate had higher rates of otorrhea (50.0% versus 35.7%; P < .01). In the 128 cultures obtained, Staphylococcus aureus was the most common organism in both groups present in 39.8% of cultures; 49% were methicillin-resistant (MRSA). Pseudomonas aeruginosa was also frequently isolated (20.0% versus 23.4%, P = .69) in children with and without cleft palate. Collectively, fluoroquinolone resistance was observed in 68.6% and 27.6% of the S. aureus and P. aeruginosa isolates, respectively, however, no differences in fluoroquinolone resistance were observed between cleft and non-cleft cohorts. Corynebacterium species were isolated more frequently in children with cleft palate (26.7% versus 6.1%, P < .01), a finding of unclear significance. CONCLUSIONS: Recalcitrant post-tympanostomy tube otorrhea is more common in children with cleft palate. MRSA was the most common isolate, which was commonly resistant to first-line fluoroquinolone therapy.

Cytotoxic activity of l-lysine alpha-oxidase against leukemia cells.

Cancer cells exhibit higher proliferation rates than normal cells, and as a consequence, a higher nutritional demand for metabolites such as amino acids. Such cells demonstrate high expression of amino acid transporters and are significantly dependent on the external uptake of amino acids. Moreover, some types of cancer cells exhibit oncogenic mutations that render them auxotrophic to certain amino acids. This metabolic difference between tumor and normal cells has been explored for developing anticancer drugs. Enzymes capable of depleting certain amino acids in the bloodstream can be employed to inhibit the proliferation of cancer cells and promote cell death. Certain microbial enzymes, such as l-asparaginase and l-amino acid oxidases, have been studied for this purpose. In this paper, we discuss the role of l-asparaginase, the only enzyme currently used as a chemotherapeutic agent. We also review the studies on a new potential antineoplastic agent, l-lysine α-oxidase, an enzyme of l-amino acid oxidase family.

The Clinicopathologic Features and Molecular Signatures of Blastoid High-Grade B Cell Lymphoma, Not Otherwise Specified.

A small subset of high-grade B-cell lymphoma (HGBL) with blastoid morphology remains poorly understood. We assessed 55 cases of blastoid HGBL, not otherwise specified (NOS) and compared their clinicopathologic characteristics with those of 81 non-blastoid HGBL-NOS and 62 blastoid HGBL with MYC and BCL2, with or without BCL6 rearrangements (double/triple-hit lymphoma [D/THL]). Patients with blastoid HGBL-NOS showed similar clinicopathologic features to patients with blastoid D/THLs and non-blastoid HGBL-NOS, except more frequently with a history of low-grade B-cell lymphoma, bone marrow involvement, and BCL2 rearrangement (P < .05) compared to the latter. MYC rearrangement (MYC-R), detected in 40% of blastoid HGBL-NOS, was associated with aggressive clinicopathologic features and poorer overall survival, even worse than that of blastoid D/THL (P < .05). Transcriptome profiling revealed a distinct gene expression pattern with differentially expressed genes enriched in MYC and P53-targeted genes in MYC-R blastoid HGBL-NOS. Fifty-two percent of blastoid HGBL-NOS had a double hit-like signature, similar to non-blastoid HGBL-NOS (P = .73). The overall survival of the blastoid HGBL-NOS group was similar to that of the blastoid D/THL group but appeared poorer than that of its non-blastoid counterparts (P = .07). Taken together, blastoid HGBL-NOS is an aggressive B-cell lymphoma that shares overlapping clinicopathologic and genetic features with non-blastoid HGBL-NOS. MYC-R in patients with blastoid HGBL-NOS identifies a highly aggressive subgroup with distinct aggressive clinicopathologic features, unique molecular signatures, and a dismal clinical outcome.

DUSP22 rearrangement is associated with a distinctive immunophenotype but not outcome in patients with systemic ALK-negative anaplastic large cell lymphoma.

DUSP22 rearrangement (R) has been associated with a favorable outcome in systemic ALK-negative anaplastic large cell lymphoma (ALCL). However, a recent study found that patients with DUSP22-R ALK-negative ALCL have a poorer prognosis than was reported initially. In this study, we compared the clinicopathological features and outcomes of patients with ALKnegative ALCL with DUSP22-R (n=22) versus those without DUSP22-R (DUSP22-NR; n=59). Patients with DUSP22-R ALCL were younger than those with DUSP22-NR neoplasms (P=0.049). DUSP22-R ALK-negative ALCL cases were more often positive for CD15, CD8, and less frequently expressed pSTAT3Tyr705, PD-L1, granzyme B and EMA (all P<0.05). TP63 rearrangement (TP63-R) was detected in three of the 66 (5%) ALK-negative ALCL cases tested and none of these cases carried the DUSP22-R. Overall survival of patients with DUSP22-R ALCL was similar to that of the patients with DUSP22-NR neoplasms regardless of International Prognostic Index score, stage, age, or stem cell transplantation status (all P>0.05), but was significantly shorter than that of the patients with ALK-positive ALCL (median overall survival 53 months vs. undefined, P=0.005). Five-year overall survival rates were 40% for patients with DUSP22-R ALCL versus 82% for patients with ALK-positive ALCL. We conclude that DUSP22-R neoplasms represent a distinctive subset of ALK-negative ALCL. However, in this cohort DUSP22-R was not associated with a better clinical outcome. Therefore, we suggest that current treatment guidelines for this subset of ALK-negative ALCL patients should not be modified at present.

Telerehabilitation with ARC Intellicare to Cope with Motor and Respiratory Disabilities: Results about the Process, Usability, and Clinical Effect of the "Ricominciare" Pilot Study.

BACKGROUND: "Ricominciare" is a single-center, prospective, pre-/post-intervention pilot study aimed at verifying the feasibility and safety of the ARC Intellicare (ARC) system (an artificial intelligence-powered and inertial motion unit-based mobile platform) in the home rehabilitation of people with disabilities due to respiratory or neurological diseases. METHODS: People with Parkinson's disease (pwPD) or post-COVID-19 condition (COV19) and an indication for exercise or home rehabilitation to optimize motor and respiratory function were enrolled. They underwent training for ARC usage and received an ARC unit to be used independently at home for 4 weeks, for 45 min 5 days/week sessions of respiratory and motor patient-tailored rehabilitation. ARC allows for exercise monitoring thanks to data from five IMU sensors, processed by an AI proprietary library to provide (i) patients with real-time feedback and (ii) therapists with information on patient adherence to the prescribed therapy. Usability (System Usability Scale, SUS), adherence, and adverse events were primary study outcomes. Modified Barthel Index (mBI), Barthel Dyspnea Index (BaDI), 2-Minute Walking Test (2MWT), Brief Fatigue Inventory (BFI), Beck Depression or Anxiety Inventory (BDI, BAI), and quality of life (EQ-5D) were also monitored pre- and post-treatment. RESULTS: A total of 21 out of 23 eligible patients were enrolled and completed the study: 11 COV19 and 10 pwPD. The mean total SUS score was 77/100. The median patients' adherence to exercise prescriptions was 80%. Clinical outcome measures (BaDI, 2MWT distance, BFI; BAI, BDI, and EQ-5D) improved significantly; no side effects were reported. CONCLUSION: ARC is usable and safe for home rehabilitation. Preliminary data suggest promising results on the effectiveness in subjects with post-COVID condition or Parkinson's disease.

Breast Implant-associated Anaplastic Large Cell Lymphoma: A Prospective Series of 52 Patients.

OBJECTIVE: We sought to evaluate patients at a single academic institution in a prospective manner to report patient presentation, clinical course, treatment, and outcomes in breast implant ALCL patients. BACKGROUND: Breast implant-associated anaplastic large cell lymphoma (breast implant ALCL) is an uncommon T cell lymphoma, which is associated with textured surface breast implants. The disease has received increasing attention over the last 20 years. Previous retrospective studies have begun to outline the clinical course of breast implant ALCL. METHODS: We prospectively followed women with cytologically proven breast implant ALCL from 2014 to 2019. Demographic, clinical, treatment, and outcome data were collected and descriptive statistics were performed on variables of interest. RESULTS: We identified 52 women with pathologically confirmed breast implant ALCL. Implants were placed for augmentation in 61.5% of women and reconstruction in 36.5% of women. All of the 41 patients with known implant information had implants with textured surface. The majority of patients presented with delayed seroma (69.2%) and without systemic symptoms (86.5%). Most patients with staging information presented with Stage IA disease. Patient outcomes were excellent with 2 disease recurrence (3.8%) and all patients ultimately achieved complete remission. CONCLUSIONS: Further evaluation of the prospective and growing database of patients with breast implant ALCL will further improve our understanding of the disease and its clinical course. Robust participation in the breast implant ALCL PROFILE registry will improve our knowledge of long-term outcomes after implant placement. Finally, increasing awareness for patients and providers will lead to earlier diagnosis and improved outcomes for patients.

Small cell/lymphohistiocytic morphology is associated with peripheral blood involvement, CD8 positivity and retained T-cell antigens, but not outcome in adults with ALK+ anaplastic large cell lymphoma.

Several morphologic variants of ALK+ anaplastic large cell lymphoma (ALCL) are recognized. The small cell (SC) and lymphohistiocytic (LH) variants are reported to be associated with poorer outcome in children with ALK + ALCL. In this study of 102 adults with ALK + ALCL, there were 18 (18%) cases of SC and/or LH variants. Patients with SC/LH ALK + ALCL more often had peripheral blood involvement than patients with non-SC/LH neoplasms (60% vs 0%, p = 0.02). There were no other significant differences in clinical features between patients with SC/LH versus non-SC/LH ALK + ALCL. Compared with non-SC/LH cases of ALK + ALCL, neoplasms with SC/LH features were more often positive for CD2 (92% vs. 36%, p = 0.0007), CD3 (81% vs. 15%, p = 0.0001), CD7 (80% vs. 37%, p = 0.03), and CD8 (54% vs. 7%, p = 0.0006). There were no other significant differences in the immunophenotype between SC/LH and non-SC/LH ALK + ALCL cases. The initial chemotherapy regimens and the response rates were similar between patients with ALK + ALCL with SC/LH patterns versus those with non-SC/LH patterns. After a median follow-up of 30.8 months (range, 0.3-208 months), patients with high (>3) International Prognostic Index (IPI) scores had significantly shorter overall survival than patients with low (<3) IPI scores (p = 0.003). However, there was no significant difference in overall or progression-free survival between patients with SC/LH versus non-SC/LH ALK + ALCL (p = 0.99 and p = 0.94, respectively). We conclude that, in adults with ALK + ALCL, SC and LH variants are associated with peripheral blood involvement and a CD8 + immunophenotype with retention of T-cell markers (CD2, CD3, and CD7). However, in contrast with children with ALK + ALCL, SC and LH variants appear to have no impact on prognosis in adults with ALK + ALCL.

Blastoid high-grade B-cell lymphoma initially presenting in bone marrow: a diagnostic challenge.

The 2016 WHO classification introduced the category of high-grade B-cell lymphoma (HGBL), which includes one poorly understood subset, blastoid-HGBL. Establishing the diagnosis and distinguishing blastoid-HGBL from B-acute lymphoblastic leukemia (B-ALL) in bone marrow can be challenging. We assessed 31 cases of blastoid-HGBL diagnosed initially in bone marrow and compared this group to 36 cases of B-ALL using immunophenotyping, fluorescence in situ hybridization, and targeted next generation sequencing analysis. The 31 blastoid-HGBL cases included 14 HGBL with MYC and BCL2 and/or BCL6 rearrangements (double hit lymphoma, DHL), 13 HGBL, not otherwise specified (NOS), and four cases with TdT expression that were difficult to classify. Compared with B-ALL, blastoid-HGBL cases more often showed increased intensity/bright expression of CD20, CD38, CD45, BCL-6, and MYC, and less frequent bright expression of CD10 and TdT. Cases of blastoid-HGBL also more frequently had MYC rearrangement, a complex karyotype and TP53 mutation (p < 0.01). With the exception of CD34, no other single factor, including TdT, was sensitive or adequately specific to distinguish blastoid-HGBL from B-ALL. We developed a scoring system using six distinctive features between 16 cases of unequivocal blastoid HGBL and 22 cases of CD34-positive B-ALL, with a score of ≥3 defining blastoid-HGBL. The system was further validated by using 15 cases of surface light chain negative, and/or CD45 dim to negative blastoid-HGBL and 14 cases of CD34-negative B-ALL. The sensitivity, specificity, positive, and negative predictive value of this scoring system were 100%, 94%, 94%, and 100%, respectively. Using this system, the four cases with TdT expression were all classified as blastoid-HGBL: three were DHL and one was HGBL-NOS. In conclusion, blastoid-HGBL shows distinctive immunophenotypic, cytogenetic, and molecular features as compared with B-ALL. The proposed scoring system can be helpful for the classification of diagnostically challenging blastoid lymphoid tumors presenting initially in the bone marrow.

Clinical Manifestations and Surgical Management of Breast Implant-Associated Anaplastic Large Cell Lymphoma: Beyond the NCCN Guidelines.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an uncommon peripheral T cell lymphoma arising in response to textured-surface breast implants. Frequently, BIA-ALCL is indolent and typically presents with peri-implant swelling after breast reconstruction or cosmetic augmentation. However, patients can present with an invasive breast or chest wall mass, palpable lymphadenopathy, or metastatic disease. The current literature is limited regarding surgical recommendations for patients with a more aggressive presentation of BIA-ALCL. This report aims to review the various clinical manifestations of BIA-ALCL, including the more advanced and less frequently encountered presentations, with an emphasis on a multidisciplinary approach, with early involvement of a surgical oncologist.

EBV-positive diffuse large B-cell lymphoma, not otherwise specified: 2022 update on diagnosis, risk-stratification, and management.

DISEASE OVERVIEW: Epstein Barr virus-positive (EBV+) diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) is an entity included in the WHO classification of lymphoid neoplasms since 2016. EBV+ DLBCL, NOS, is an aggressive B-cell lymphoma associated with EBV infection, and a poor prognosis with standard chemotherapeutic approaches. DIAGNOSIS: The diagnosis is made through a careful pathological evaluation. Detection of EBV-encoded RNA (EBER) is considered standard for diagnosis; however, a clear cutoff for percentage of positive cells has not been defined. The differential diagnosis includes plasmablastic lymphoma (PBL), DLBCL associated with chronic inflammation, primary effusion lymphoma (PEL), among others. RISK-STRATIFICATION: The International Prognostic Index (IPI) and the Oyama score can be used for risk-stratification. The Oyama score includes age >70 years and presence of B symptoms. The expression of CD30 and PD-1/PD-L1 are emerging as potential adverse but targetable biomarkers. MANAGEMENT: Patients with EBV+ DLBCL, NOS, should be staged and managed following similar guidelines than patients with EBV-negative DLBCL. EBV+ DLBCL, NOS, however, might have a worse prognosis than EBV-negative DLBCL in the era of chemoimmunotherapy. Therefore, the inclusion of patients in clinical trials when available is recommended. There is an opportunity to study and develop targeted therapy in the management of patients with EBV+ DLBCL, NOS.

Breast and thyroid cancer: A multicenter study with Accrual to Clinical Trials Network.

OBJECTIVE: To investigate a possible link between breast and thyroid cancer. METHODS: A multicenter retrospective review of patients in the electronic medical records of six Accrual to Clinical Trial (ACT) institutions with both breast cancer and thyroid carcinoma. Each center queried its data using a predefined data dictionary. Information on thyroid and breast cancer included dates of diagnosis, histology, and patient demographics. RESULTS: A random-effects model was used. There were 4.24 million women's records screened, 44 605 with breast cancer and 11 846 with thyroid cancer. The relative risks observed at each institution ranged from 0.49 to 13.47. The combined risk ratio (RR) estimate was 1.77 (95% confidence interval: 0.50-5.18). CONCLUSION: There was no association between the risk of developing thyroid cancer and being a breast cancer survivor compared to no history of breast cancer, but the range of relative risks among the participating institutions was wide. Our findings warrant further study of more institutions with larger sample size. Additionally, further analysis of the significance of regional RR differences may be enlightening.

Malignant Peritoneal Mesothelioma Associated With Endometriosis: A Clinicopathologic Study of 15 Cases.

Only a few cases of malignant peritoneal mesothelioma (MPeM) associated with endometriosis have been published; with chronic inflammation of the peritoneum associated with the latter being postulated as an inducing factor in the pathogenesis of this tumor. We assessed the clinicopathologic characteristics of MPeM associated with endometriosis to determine if there were other factors besides inflammation that may contribute to the pathogenesis in this patient population. Fifteen MPeM associated with endometriosis were retrieved from our files. Most presented with abdominal/pelvic pain, mass or distention; median age was 45 yr. Only 16% of patients had a history of asbestos exposure. In contrast, a third of the patients had a personal history of other neoplasms, and >80% had a family history of malignancies. Although most tumors had gross and microscopic features typical of MPeM, some had confounding features including "adhesion-like" appearance or gelatinous cysts/nodules, and signet ring cells. Tumors were epithelioid (9) and biphasic (6). MPeM was misdiagnosed as Müllerian carcinoma in 40% of cases. All patients (n=15) had cytoreductive surgery in addition to other therapies. Only 2/12 patients died of disease (17%). The 3- and 5-yr overall survival was 90%. MPeM associated with endometriosis tends to occur in patients with personal/familial history of malignancies, which may be a predisposing factor. In light of this finding, the role of endometriosis in the pathogenesis of MPeM is likely less relevant. The favorable outcome seen in these patients may be related to germline mutations or the hormonal milieu and needs further investigation.

Current Trends in Precision Medicine and Next-Generation Sequencing in Head and Neck Cancer.

OPINION STATEMENT: As the field of oncology enters the era of precision medicine and targeted therapies, we have come to realize that there may be no single "magic bullet" for patients with head and neck cancer. While immune check point inhibitors and some targeted therapeutics have shown great promise in improving oncologic outcomes, the current standard of care in most patients with head and neck squamous cell carcinoma (HNSCC) remains a combination of surgery, radiation, and/or cytotoxic chemotherapy. Nevertheless, advances in precision medicine, next-generation sequencing (NGS), and targeted therapies have a potential future in the treatment of HNSCC. These roles include increased patient treatment stratification based on predictive biomarkers or targetable mutations and novel combinatorial regimens with existing HNSCC treatments. There remain challenges to precision medicine and NGS in HNSCC, including intertumor and intratumor heterogeneity, challenging targets, and need for further trials validating the utility of NGS and precision medicine. Additionally, there is a need for evidence-based practice guidelines to assist clinicians on how to appropriately incorporate NGS in care for HNSCC. In this review, we describe the current state of precision medicine and NGS in HNSCC and opportunities for future advances in this challenging but important field.

Total laryngectomy negatively impacts sinonasal and olfactory-specific quality of life.

PURPOSE: The purpose of this study is to characterize deficits in olfactory-specific and sinonasal-specific QoL after total laryngectomy (TL) with validated patient reported outcome measures. METHODS: Thirty patients who had a TL were prospectively enrolled. Patient demographics, as well as scores from the Questionnaire of Olfactory Disorders Negative Statements (QOD-NS) and the Sino-nasal Outcome Test-22 (SNOT-22) were collected. Univariate analysis was performed to assess associations between patient characteristics and QoL scores. RESULTS: The average QOD-NS score was 37.9 ± 11.4 (<38.5 is considered abnormal) and average SNOT-22 score was 32.0 ± 3.8 (>20 indicates a moderate/severe impact on QoL). The abnormal QOD-NS group had a greater percentage of former smokers compared to the normal group (77.8% vs. 58.1%; P = 0.56) and more median days from surgery compared to the normal group (904 vs. 477 days; P = 0.24). CONCLUSIONS: Olfactory dysfunction associated with TL results in blunting of olfactory-specific QoL.