The Gross-to-Scope Program for Gross Room Personnel: An Innovative Initiative for Providing Case Follow-Up and Education to "Close the Pathology Loop".

Gross room personnel (GRP) work alongside pathologists in grossing, frozen section, and autopsy. We observed that gross room personnel desire follow-up and feedback on the specimens they gross or autopsies they perform. Our goal was to create a sustainable educational program for gross room personnel. Our primary focus was to impact team dynamic, morale, and fulfillment. We assessed the need for an educational program through a preprogram survey, which contained 11 subjective statements scored on a scale from 1 to 10 (1-strongly disagree and 10-strongly agree). These statements assessed topics of current follow-up and team dynamic (core statements), perceived effect of current follow-up, and prospective impact of case follow-up. Core statements received relatively low scores (ie, the perception of being "an integral part in making a diagnosis" received only a mean score of 6.7). In response, we established the Gross-to-Scope educational program hosted by pathology trainees and attendings. This program is comprised of monthly one-hour conferences to discuss/review cases and highlight special topics of interest (ie, "What is a radial margin anyway?"). We distributed the same surveys after the first and fourth conferences and found a statistically significant increase in the mean responses to core statements after the first conference (P = .041). The trend is similar after four conferences. Overall our program addresses various needs by providing educational opportunities for gross room personnel, which strengthens morale and recognizes hard work, and by fostering a working relationship between gross room personnel and pathologists.

Squamous Cell Carcinoma of the Bladder Is Not Associated With High-risk HPV.

OBJECTIVE: To evaluate the clinical features, pathologic features, and prevalence of human papilloma virus (HPV) in squamous cell carcinoma (SCC) of the bladder. SCC of the bladder is known to be associated with conditions that cause chronic inflammation/irritation. The literature is inconsistent regarding the association of HPV with pure SCC of the bladder. METHODS: A multi-institutional study identified cases of SCC of the bladder. Pure squamous histology and the absence of urothelial carcinoma in situ were required for inclusion. Clinical and pathologic features were collected, and tissues were evaluated for high-risk HPV using p16 immunohistochemistry and in situ hybridization. RESULTS: We identified 207 cases of SCC of the bladder. Risk factors for bladder cancer included smoking (133/207, 64%) and chronic bladder irritation (83/207, 40%). The majority (155/207, 75%) of patients had > pT2 disease. Mean tumor size was 5.6 ± 3.0 cm and 36/207 (17%) patients had lymph node positive disease. p16 immunohistochemistry was positive in 52/204 (25%) cases but high-risk HPV was identified with in situ hybridization in only 1 (0.5%) case. Tumor size, stage, number of lymph nodes removed, number of positive lymph nodes, lymphovascular invasion, perineural invasion, and positive margins each were associated with cancer-specific mortality when adjusted for demographic factors. A multivariate analysis of variable importance further revealed sex and race as important factors in predicting cancer-specific mortality. CONCLUSION: SCC of the bladder is an aggressive histologic subtype. Although bladder SCC can express p16, it is not typically associated with high-risk HPV, although rare cases can occur.

Pembrolizumab-Induced Thyroiditis.

Immune checkpoint inhibitors act to restore T cell-mediated antitumor immunity. By this nature, these cancer immunotherapy drugs are associated with various immune-related adverse events such as thyroid dysfunction. We describe a case of thyrotoxicosis secondary to a programmed cell death 1 (PD-1) immune checkpoint inhibitor, pembrolizumab. A 30-year-old female was started on pembrolizumab immunotherapy for stage III small cell carcinoma of the ovary, hypercalcemic type. Thirteen days after her second cycle of therapy, she presented with symptoms consistent with thyrotoxicosis. A thyroiditis was diagnosed by thyroid function tests and ultrasonography. She was originally treated with prednisone and metoprolol for possible Grave's disease. Pertechnetate thyroid scan was more consistent with thyroiditis secondary to pembrolizumab. She underwent a total thyroidectomy 10 days after initial presentation for refractory thyrotoxicosis despite maximal medical therapy. Her symptoms resolved and thyroid function tests significantly improved. Pathology was consistent with severe thyroiditis. Immune microenvironment may play a role in the expression of programmed cell death protein 1 ligand 1 (PD-L1). Chronic inflammation surrounding tumor upregulates PD-L1 expression on tumor cells by the release of cytokines, which acts to inhibit tumor destruction. We suggest that our patient had an undetected chronic inflammation of the thyroid, specifically Hashimoto's thyroidits, which predisposed her to thyroid destruction when taking pembrolizumab. Understanding that an inflammatory environment impacts thyroid toxicity to PD-1 inhibitor therapy is novel and should be further studied.

Innervation of cervical carcinoma is mediated by cancer-derived exosomes.

OBJECTIVE: Recently, our laboratory identified sensory innervation within head and neck squamous cell carcinomas (HNSCCs) and subsequently defined a mechanism whereby HNSCCs promote their own innervation via the release of exosomes that stimulate neurite outgrowth. Interestingly, we noted that exosomes from human papillomavirus (HPV)-positive cell lines were more effective at promoting neurite outgrowth than those from HPV-negative cell lines. As nearly all cervical tumors are HPV-positive, we hypothesized that these findings would extend to cervical cancer. METHODS: We use an in vitro assay with PC12 cells to quantify the axonogenic potential of cervical cancer exosomes. PC12 cells are treated with cancer-derived exosomes, stained with the pan-neuronal marker (ß-III tubulin) and the number of neurites quantified. To assess innervation in cervical cancer, we immunohistochemically stained cervical cancer patient samples for ß-III tubulin and TRPV1 (sensory marker) and compared the staining to normal cervix. RESULTS: Here, we show the presence of sensory nerves within human cervical tumors. Additionally, we show that exosomes derived from HPV-positive cervical cancer cell lines effectively stimulate neurite outgrowth. CONCLUSIONS: These data identify sensory nerves as components of the cervical cancer microenvironment and suggest that tumor- derived exosomes promote their recruitment.