Incidentally Diagnosed Low-Grade Primary Peritoneal Serous Carcinoma Within the Umbilical Hernia Sac in a Male: A Report of an Extremely Rare Case and Review of the Literature.

Primary peritoneal serous carcinoma (PPSC) is a rare tumor that develops in the peritoneum. PPSC originates from embryonic nests of Müllerian cells in the peritoneum, which are also present in the epithelium of the ovary. This similarity explains the histopathological resemblance between PPSC and low-grade serous ovarian carcinoma. While PPSC primarily affects women, it is an extremely rare occurrence in males, and it is believed that the significant difference in diagnosis rates between males and females is due to the inhibition of Müllerian system growth by substances produced by male Sertoli cells. These substances are present at higher levels in males, which may prevent the development of Müllerian system-derived tumors in men. We describe a 65-year-old male patient who presented for elective bariatric surgery and umbilical hernia repair, and an incidental finding of low-grade PPSC was made based on hernia sac pathology. The patient underwent further management, including tumor debulking and hyperthermic intraperitoneal chemotherapy (HIPEC), with positive outcomes. Long-term follow-up and oral letrozole treatment are planned.

Improvement in Hearing Loss Following Posterior Fossa Arachnoid Cyst Fenestration: A Case Study.

Arachnoid cysts are abnormal intradural collections of cerebrospinal fluid. For posterior fossa arachnoid cysts (PFACs), symptoms vary greatly, often relating to cranial nerve impingement and/or hydrocephalus. Literature on long-term symptomatic and radiographic follow-up of PFACs is lacking. This case study describes a 32-year-old man who presented with headaches and left-sided hearing loss and was found to have a large left-sided cerebellopontine angle arachnoid cyst with syrinx and ventriculomegaly. After PFAC fenestration and excision, his headaches resolved and his hearing markedly improved. At the one-year postoperative evaluation, symptom improvement persisted, and MRI demonstrated a stable decreased cyst and near-complete resolution of his syrinx.

Comparative analysis of animal lifespan.

Comparative studies of aging are a promising approach to identifying general properties of and processes leading to aging. While to date, many comparative studies of aging in animals have focused on relatively narrow species groups, methodological innovations now allow for studies that include evolutionary distant species. However, comparative studies of aging across a wide range of species that have distinct life histories introduce additional challenges in experimental design. Here, we discuss these challenges, highlight the most pressing problems that need to be solved, and provide suggestions based on current approaches to successfully carry out comparative aging studies across the animal kingdom.

Recent Advances in Genitourinary Tumors Updates From the 5th Edition of the World Health Organization Blue Book Series.

CONTEXT.­: Urinary and Male Genital Tumours is the 8th volume of the World Health Organization Classification of Tumours series, 5th edition. Released in hard copy in September 2022, it presents an update to the classification of male genital and urinary tumors in the molecular age. Building upon previous volumes in this series, significant effort has been made to harmonize terminology across organ systems for biologically similar tumors (eg, neuroendocrine tumors). Genomic terminology has been standardized and genetic syndromes covered more comprehensively. This review presents a concise summary of this volume highlighting new entities, notable modifications relative to the 4th edition, and elements of relevance to routine clinical practice. OBJECTIVE.­: To provide a comprehensive update on the World Health Organization classification of urinary and male genital tumors, highlighting updated diagnostic criteria and terminology. DATA SOURCES.­: The 4th and 5th editions of the World Health Organization Classification of Tumours: Urinary and Male Genital Tumours. CONCLUSIONS.­: The World Health Organization has made several changes in the 5th edition of the update on urinary and male genital tumors that pathologists need to be aware of for up-to-date clinical practice.

Multilineage Pituitary Neuroendocrine Tumors (PitNETs) Expressing PIT1 and SF1.

PitNETs are usually restricted in their cytodifferentiation to only one of 3 lineages dictated by expression of the pituitary transcription factors (TFs) PIT1, TPIT, or SF1. Tumors that show lineage infidelity and express multiple TFs are rare. We searched the pathology files of 4 institutions for PitNETs with coexpression of PIT1 and SF1. We identified 38 tumors in 21 women and 17 men, average age 53 (range 21-79) years. They represented 1.3 to 2.5% of PitNETs at each center. Acromegaly was the presentation in 26 patients; 2 had central hyperthyroidism associated with growth hormone (GH) excess and one had significantly elevated prolactin (PRL). The remainder had mass lesions with visual deficits, hypopituitarism, and/or headaches. Tumor size ranged from 0.9 to 5 cm; all 7 lesions smaller than 1 cm were associated with acromegaly. Larger lesions frequently invaded the cavernous sinuses. Four cases represented a second attempt at surgical resection. PIT1 was usually diffusely positive but 5 cases had variable (patchy or focal) staining. SF1 reactivity was variable in intensity but diffuse in all but 2 cases. GATA3 data, available in 14 cases, identified diffuse positivity in 5 and focal staining in 1. GH was expressed in all but 5 tumors, PRL and thyrotropin (TSH) were expressed in 14 and 13, respectively, follicle-stimulating hormone (FSH) in 11 of 18, and luteinizing hormone (LH) in 4 of 17. Keratin staining patterns were diffuse perinuclear/membranous in 27, variable perinuclear in 4, and negative in 3; scattered fibrous bodies were seen in 5 and diffuse fibrous bodies in 1. Ki67 labeling index ranged from < 1 to 7.9%. In 3 cases, these tumors represented one of multiple synchronous PitNETs; a separate corticotroph tumor was seen in 2 patients and one patient had 2 additional discrete lesions, a sparsely granulated lactotroph, and a pure gonadotroph tumor comprising a triple tumor. PitNETs expressing PIT1 and SF1 represent multilineage PitNETs. These rare tumors have variable clinical and morphological features, most often presenting as large tumors with GH excess and occasionally as one of multiple synchronous PitNETs of distinct lineages.

The Mucosal Manifestations of Syphilis in the Head and Neck.

Objectives: Syphilis is a resurging disease which can present itself in many ways, including lesions within the head and neck mucosa. Some of these lesions may clinically mimic oral malignancies. This literature review aims to better characterize the mucosal presentations of syphilis. Methods: PubMed, EMBASE, and clinicaltrials.gov were searched for full-text, English articles published from 1950 to 2022 that reported patients with head and neck mucosal manifestations of syphilis. Articles were screened according to PRISMA guidelines. Results: One hundred forty-three manuscripts documenting 236 individual patients were included in the review. Patients with secondary syphilis accounted for 62% of patients presenting with head and neck mucosal lesions. The most common lesions found in primary and secondary syphilis were ulcerations, primarily found on the tongue, lips, and palate. While serologic studies are the gold standard for diagnosing syphilis, biopsy of these lesions have characteristic syphilitic changes. Conclusions: Syphilis' nickname of "The great imitator" remains to be true, and the head and neck mucosal manifestations of this disease can resemble commonly seen malignancies. Awareness of this disease and its lesions is prudent given the rising incidence of syphilis within the United States.

Modeling collective cell behavior in cancer: Perspectives from an interdisciplinary conversation.

Collective cell behavior contributes to all stages of cancer progression. Understanding how collective behavior emerges through cell-cell interactions and decision-making will advance our understanding of cancer biology and provide new therapeutic approaches. Here, we summarize an interdisciplinary discussion on multicellular behavior in cancer, draw lessons from other scientific disciplines, and identify future directions.

Recent Advances in the Classification of Gynecological Tract Tumors: Updates From the 5th Edition of the World Health Organization "Blue Book".

CONTEXT.­: The World Health Organization Classification of Tumours: Female Genital Tract Tumors, 5th edition, published in September 2020, comes 6 years after the 4th edition, and reflects the monumental leaps made in knowledge about the biology of gynecological tumors. Major changes include revised criteria for the assignment of the site of origin of ovarian and fallopian tube tumors, a revision in the classification of squamous and glandular lesions of the lower genital tract based on human papillomavirus association, and an entire chapter devoted to genetic tumor syndromes. This article highlights the changes in the 5th edition relative to the 4th edition, with a focus on areas of value to routine clinical practice. OBJECTIVE.­: To provide a comprehensive update on the World Health Organization classification of gynecological tumors, highlighting in particular updated diagnostic criteria and terminology. DATA SOURCES.­: The 4th and 5th editions of the World Health Organization Classification of Tumours. CONCLUSIONS.­: The World Health Organization has made several changes in the 5th edition of the update on female genital tumors. Awareness of the changes is needed for pathologists' translation into contemporary practice.

Functions of HP1 proteins in transcriptional regulation.

In eukaryotes, DNA is packaged into chromatin, which presents significant barriers to transcription. Non-histone chromatin proteins such as the Heterochromatin Protein 1 (HP1) proteins are critical regulators of transcription, contributing to gene regulation through a variety of molecular mechanisms. HP1 proteins are highly conserved, and many eukaryotic genomes contain multiple HP1 genes. Given the presence of multiple HP1 family members within a genome, HP1 proteins can have unique as well as shared functions. Here, we review the mechanisms by which HP1 proteins contribute to the regulation of transcription. Focusing on the Drosophila melanogaster HP1 proteins, we examine the role of these proteins in regulating the transcription of genes, transposable elements, and piRNA clusters. In D. melanogaster, as in other species, HP1 proteins can act as transcriptional repressors and activators. The available data reveal that the precise impact of HP1 proteins on gene expression is highly context dependent, on the specific HP1 protein involved, on its protein partners present, and on the specific chromatin context the interaction occurs in. As a group, HP1 proteins utilize a variety of mechanisms to contribute to transcriptional regulation, including both transcriptional (i.e. chromatin-based) and post-transcriptional (i.e. RNA-based) processes. Despite extensive studies of this important protein family, open questions regarding their functions in gene regulation remain, specifically regarding the role of hetero- versus homodimerization and post-translational modifications of HP1 proteins.

Sex-specific aging in animals: Perspective and future directions.

Sex differences in aging occur in many animal species, and they include sex differences in lifespan, in the onset and progression of age-associated decline, and in physiological and molecular markers of aging. Sex differences in aging vary greatly across the animal kingdom. For example, there are species with longer-lived females, species where males live longer, and species lacking sex differences in lifespan. The underlying causes of sex differences in aging remain mostly unknown. Currently, we do not understand the molecular drivers of sex differences in aging, or whether they are related to the accepted hallmarks or pillars of aging or linked to other well-characterized processes. In particular, understanding the role of sex-determination mechanisms and sex differences in aging is relatively understudied. Here, we take a comparative, interdisciplinary approach to explore various hypotheses about how sex differences in aging arise. We discuss genomic, morphological, and environmental differences between the sexes and how these relate to sex differences in aging. Finally, we present some suggestions for future research in this area and provide recommendations for promising experimental designs.

The Epigenome and Beyond: How Does Non-genetic Inheritance Change Our View of Evolution?

Evidence from across the tree of life suggests that epigenetic inheritance is more common than previously thought. If epigenetic inheritance is indeed as common as the data suggest, this finding has potentially important implications for evolutionary theory and our understanding of how evolution and adaptation progress. However, we currently lack an understanding of how common various epigenetic inheritance types are, and how they impact phenotypes. In this perspective, we review the open questions that need to be addressed to fully integrate epigenetic inheritance into evolutionary theory and to develop reliable predictive models for phenotypic evolution. We posit that addressing these challenges will require the collaboration of biologists from different disciplines and a focus on the exploration of data and phenomena without preconceived limits on potential mechanisms or outcomes.

Measuring the Efficacy of Pathology Career Recruitment Strategies in US Medical Students.

CONTEXT.­: Multiple articles and surveys in the literature suggest that medical students find a career in pathology undesirable and believe it is disproportionately focused primarily on the autopsy. OBJECTIVE.­: To measure the effect of applied interventions on medical student attitudes about the field of pathology. DESIGN.­: This prospective study involving medical students from first through fourth year was conducted as a pilot study in 2 medical schools in the United States. A 2-part anonymous survey regarding interest in pathology as a career and familiarity with the specialty using a 10-point scale was given to first- and second-year medical students before and after they listened to a 10-minute pathology career presentation. The same survey was given to third- and fourth-year medical students before and after a 4-week pathology elective. RESULTS.­: A total of 121 and 83 students responded to the survey before and after the intervention, respectively. Of the 121 students who responded to the survey before the intervention, 106 (87.6%) had not spent significant time in a pathology laboratory before the intervention. The majority of responses in interest in career, job responsibilities, and features of pathologists before and after the intervention demonstrated a statistically significant difference (P < .001). We compared survey scores of presentation versus 4-week rotation groups before and after the intervention. Students who experienced the presentation did not differ from students who experienced the rotation in the majority of questions related to interest in career, job responsibilities, and features of pathologists. CONCLUSIONS.­: Our study suggests that pathology exposure strategies can have a beneficial effect on student perceptions of the field and consideration of a career in pathology. Overall, the presentation intervention seemed to have the greatest effect on the first- and second-year students.

The Drosophila HP1 family is associated with active gene expression across chromatin contexts.

Drosophila Heterochromatin Protein 1a (HP1a) is essential for heterochromatin formation and is involved in transcriptional silencing. However, certain loci require HP1a to be transcribed. One model posits that HP1a acts as a transcriptional silencer within euchromatin while acting as an activator within heterochromatin. However, HP1a has been observed as an activator of a set of euchromatic genes. Therefore, it is not clear whether, or how, chromatin context informs the function of HP1 proteins. To understand the role of HP1 proteins in transcription, we examined the genome-wide binding profile of HP1a as well as two other Drosophila HP1 family members, HP1B and HP1C, to determine whether coordinated binding of these proteins is associated with specific transcriptional outcomes. We found that HP1 proteins share many of their endogenous binding targets. These genes are marked by active histone modifications and are expressed at higher levels than nontarget genes in both heterochromatin and euchromatin. In addition, HP1 binding targets displayed increased RNA polymerase pausing compared with nontarget genes. Specifically, colocalization of HP1B and HP1C was associated with the highest levels of polymerase pausing and gene expression. Analysis of HP1 null mutants suggests these proteins coordinate activity at transcription start sites to regulate transcription. Depletion of HP1B or HP1C alters expression of protein-coding genes bound by HP1 family members. Our data broaden understanding of the mechanism of transcriptional activation by HP1a and highlight the need to consider particular protein-protein interactions, rather than broader chromatin context, to predict impacts of HP1 at transcription start sites.

Exercise-induced changes in climbing performance.

Exercise is recommended to promote health and prevent a range of diseases. However, how exercise precipitates these benefits is unclear, nor do we understand why exercise responses differ so widely between individuals. We investigate how climbing ability in Drosophila melanogaster changes in response to an exercise treatment. We find extensive variation in baseline climbing ability and exercise-induced changes ranging from -13% to +20% in climbing ability. Climbing ability, and its exercise-induced change, is sex- and genotype-dependent. GWASs implicate 'cell-cell signalling' genes in the control of climbing ability. We also find that animal activity does not predict climbing ability and that the exercise-induced climbing ability change cannot be predicted from the activity level induced by the exercise treatment. These results provide promising new avenues for further research into the molecular pathways controlling climbing activity and illustrate the complexities involved in trying to predict individual responses to exercise.

A Case of Retroperitoneal Synovial Sarcoma in Pregnancy Treated with Antepartum Doxorubicin plus Ifosfamide Chemotherapy.

We report a case of a 25-year-old pregnant woman diagnosed with a large, unresectable retroperitoneal synovial sarcoma. Successful neoadjuvant treatment with doxorubicin plus ifosfamide prepartum and continuing postpartum resulted in significant disease response allowing for later tumor resection. Following the first prepartum chemotherapy cycle, a decreased amniotic fluid index was noted, representing a potential complication of chemotherapy. Induction of labor was performed at 33 weeks gestation with excellent outcome in the newborn. This case highlights the complex medical decision-making process in the setting of cancer diagnosed during pregnancy, balancing oncologic and obstetric concerns, and to our knowledge is only the second reported case of synovial sarcoma treated with neoadjuvant cytotoxic chemotherapy in the antepartum period.

GWAS reveal a role for the central nervous system in regulating weight and weight change in response to exercise.

Body size and weight show considerable variation both within and between species. This variation is controlled in part by genetics, but also strongly influenced by environmental factors including diet and the level of activity experienced by the individual. Due to the increasing obesity epidemic in much of the world, there is considerable interest in the genetic factors that control body weight and how weight changes in response to exercise treatments. Here, we address this question in the Drosophila model system, utilizing 38 strains of the Drosophila Genetics Reference Panel. We use GWAS to identify the molecular pathways that control weight and weight changes in response to exercise. We find that there is a complex set of molecular pathways controlling weight, with many genes linked to the central nervous system (CNS). The CNS also plays a role in the weight change with exercise, in particular, signaling from the CNS. Additional analyses revealed that weight in Drosophila is driven by two factors, animal size, and body composition, as the amount of fat mass versus lean mass impacts the density. Thus, while the CNS appears to be important for weight and exercise-induced weight change, signaling pathways are particularly important for determining how exercise impacts weight.

Plasma Cell Myeloma Within a Renal Cell Carcinoma, an Intimate Histologic Relationship: A Case Report and Literature Review.

The coexistence of two separate malignancies in a patient is a rare occurrence. Even more infrequent is the coexistence of a hematologic malignancy and a solid tumor. However, the relationship between renal cell carcinoma (RCC) and plasma cell myeloma (PCM) has been reported in previous studies. These studies described synchronous cases of RCC and PCM and demonstrated that this situation occurs more frequently than expected by probability calculations. We present, what we believe to be, the first reported case of RCC directly and physically involved by PCM and, we review the literature on the association between these malignancies and explore possible mechanisms for their higher than expected association. In describing this case, emphasis is made to describe unique histologic findings that could further support a more direct and intimate association between these tumors.

Primary Cutaneous Gamma/Delta T-cell Lymphoma and Hemophagocytic Lymphohistiocytosis Associated With AIDS.

Primary cutaneous gamma delta T-cell lymphoma (PCGD-TCL) is a rare lymphoma that makes up less than 1% of all cutaneous T-cell lymphomas. Patients with PCGD-TCL typically present with rapidly progressing plaques and ulceronecrotic nodules most frequently located on extremities without lymph node or bone marrow involvement. The overall prognosis is poor with a median overall survival of approximately 15 months. This case highlights a patient with concomitant PCGD-TCL, hemophagocytic lymphohistiocytosis, and human immunodeficiency virus-1-acquired immunodeficiency syndrome. There is a paucity of case reports describing PCGD-TCL and there are no evidence-based treatment recommendations. Further studies are needed to optimize strategies to treat patients with these diseases.

Social Media Engagement at Academic Conferences: Report of the Association of Pathology Chairs 2018 and 2019 Annual Meeting Social Media Committee.

The use of social media at academic conferences is expanding, and platforms such as Twitter are used to share meeting content with the world. Pathology conferences are no exception, and recently, pathology organizations have promoted social media as a way to enhance meeting exposure. A social media committee was formed ad hoc to implement strategies to enhance social media involvement and coverage at the 2018 and 2019 annual meetings of the Association of Pathology Chairs. This organized approach resulted in an 11-fold increase in social media engagement compared to the year prior to committee formation (2017). In this article, the social media committee reviews the strategies that were employed and the resultant outcome data. In addition, we categorize tweets by topic to identify the topics of greatest interest to meeting participants, and we discuss the differences between Twitter and other social media platforms. Lastly, we review the existing literature on this topic from 23 medical specialties and health care fields.