Metastatic prostatic adenocarcinoma presenting as generalized lymphadenopathy unmasked by a COVID booster vaccine.

Key Clinical Message: Lymphadenopathy following recent immunization is usually regional. Generalized lymphadenopathy should arouse suspicion for alternative underlying pathology. Prostate adenocarcinoma should be considered in the differential diagnosis for malignancy in an elderly male patient. Metastatic prostate adenocarcinoma can have good prognostic outcomes if treatment is started promptly, even in the setting of widespread disease. Abstract: Generalized lymphadenopathy is commonly attributed to infectious causes or malignancy, often lymphoproliferative disorders. We present a rare case of metastatic prostate cancer diagnosed after initially presenting as generalized lymphadenopathy following a coronavirus disease 2019 (COVID) booster vaccination. A 70-year-old Hispanic male presented with left lower quadrant abdominal pain, nausea, headache, myalgia, severe constipation, and a right-sided neck swelling that had been increasing in size since the day of his vaccination. Computed tomography (CT) scans of soft tissue neck, chest, abdomen, and pelvis with contrast showed extensive lymphadenopathy. Ultrasound-guided biopsy results of the enlarged right supraclavicular node and prostate revealed histopathology consistent with that of prostate acinar adenocarcinoma. He started on bicalutamide for 4 weeks, transitioned to gonadotropin releasing hormone analogue (leuprolide) injections every 3 months and oral androgen receptor signaling inhibitor (abiraterone with prednisone daily). PSA level declined from 121 ng/mL at diagnosis to 1.3 ng/mL after 3 months of therapy, and repeat imaging showed marked improvement in the size of his mediastinal, retroperitoneal, and pelvic lymphadenopathy. To the best of our knowledge, this is the first case reported of a COVID vaccine booster uncovering lymphadenopathy leading to the diagnosis of metastatic prostate cancer.

Association between prostate size and glandular tissue volume of the peripheral zone via novel combined MRI and histopathology: possible pathophysiological implications on prostate cancer development.

PURPOSE: Benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are the two most prevalent urologic diseases affecting elderly men. An inverse relationship between BPH/prostate size and PCa incidence is well documented in the current literature, but the precise mechanism is poorly understood. This study aims to investigate the effect of total prostate volume on total glandular tissue volume of the peripheral zone via a novel combination of magnetic resonance imaging (MRI) and histo-anatomical imaging. METHODS: 42 male patients between ages 53-79 years underwent both radical prostatectomy and pre-operative MRI scans. Prostate sizes ranged from 14.8-133.3cc. Quantitative measurements of surgical capsule thickness and glandular epithelial cell density within the peripheral zone (PZ) were obtained on histo-anatomical slides using computer-based imaging software. Quantitative prostatic zonal measurements were obtained from MRI scans. Combining MRI- and histopathology-obtained parameters allowed measurement of the total glandular tissue volume of the PZ (GVPZ). Statistical analysis was performed to identify associations between total prostate volume (TPV) and GVPZ. RESULTS: The Mann-Whitney U-test showed significant decreases in GVPZ in larger prostates when compared to smaller prostates. CONCLUSIONS: Combined MRI and histopathology techniques provide a novel method for accurate measuring of glandular tissue content within the prostatic PZ. The findings of this pilot study support the hypothesis of PZ compression by an expanding transition zone in large BPH prostates, leading to atrophy of PZ glandular tissue. As the majority of PCa originates in the PZ, this dynamic process may explain the protective effect of large BPH prostates against PCa development.

Dishevelled 2 regulates cancer cell proliferation and T cell mediated immunity in HER2-positive breast cancer.

BACKGROUND: Dishevelled paralogs (DVL1, 2, 3) are key mediators of Wnt pathway playing a role in constitutive oncogenic signaling influencing the tumor microenvironment. While previous studies showed correlation of ß-catenin with T cell gene expression, little is known about the role of DVL2 in modulating tumor immunity. This study aimed to uncover the novel interaction between DVL2 and HER2-positive (HER2+) breast cancer (BC) in regulating tumor immunity and disease progression. METHODS: DVL2 loss of function studies were performed with or without a clinically approved HER2 inhibitor, Neratinib in two different HER2+ BC cell lines. We analyzed RNA (RT-qPCR) and protein (western blot) expression of classic Wnt markers and performed cell proliferation and cell cycle analyses by live cell imaging and flow cytometry, respectively. A pilot study in 24 HER2+ BC patients was performed to dissect the role of DVL2 in tumor immunity. Retrospective chart review on patient records and banked tissue histology were performed. Data were analyzed in SPSS (version 25) and GraphPad Prism (version 7) at a significance p < 0.05. RESULTS: DVL2 regulates the transcription of immune modulatory genes involved in antigen presentation and T cell maintenance. DVL2 loss of function down regulated mRNA expression of Wnt target genes involved in cell proliferation, migration, invasion in HER2+ BC cell lines (±Neratinib). Similarly, live cell proliferation and cell cycle analyses reveal that DVL2 knockdown (±Neratinib) resulted in reduced proliferation, higher growth arrest (G1), limited mitosis (G2/M) compared to non-targeted control in one of the two cell lines used. Analyses on patient tissues who received neoadjuvant chemotherapy (n = 14) further demonstrate that higher DVL2 expression at baseline biopsy pose a significant negative correlation with % CD8α levels (r = - 0.67, p < 0.05) while have a positive correlation with NLR (r = 0.58, p < 0.05), where high NLR denotes worse cancer prognosis. These results from our pilot study reveal interesting roles of DVL2 proteins in regulating tumor immune microenvironment and clinical predictors of survival in HER2+ BC. CONCLUSION: Our study demonstrates potential immune regulatory role of DVL2 proteins in HER2+ BC. More in-depth mechanistic studies of DVL paralogs and their influence on anti-tumor immunity may provide insight into DVLs as potential therapeutic targets benefiting BC patients.

Tumor-Infiltrating Lymphocytes (TILs) as a Biomarker of Abscopal Effect of Cryoablation in Breast Cancer: A Pilot Study.

BACKGROUND: Morphological evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer is gaining momentum as an immunological biomarker. This experiment evaluates the role of TILs in distant tumors as a measure of abscopal effect from cryoablation of breast cancer. METHODS: BALB/c mice underwent bilateral orthotopic transplant with 4T1-12B (triple-negative) cells. At 2 weeks, left tumors were treated by either resection (standard of care group) or cryoablation (intervention group) followed by resection of the distant right tumors 1 week posttreatment. TIL scores were calculated from hematoxylin and eosin-stained sections and phenotyped for cytotoxic T-lymphocyte (CTL) markers by immunofluorescence. Primarily resected tumors served as baseline (Tbaseline), whereas resected distant right-sided served as the readout for abscopal effect (AbsRes or AbsCryo). Mice were monitored for tumor recurrence and metastasis. RESULTS: The AbsCryo had a significant mean (SD) increase in stromal (2.8 [1.1]%; p = 0.015) and invasive margin TILs (50 [12]%; p = 0.02) compared with TBaseline (1.0 [0]% and 31 [4.9]%, respectively). CTL phenotyping revealed a significant increase in mean (SD) CD8+ T cells (15.7 [12.1]; p = 0.02) and granzyme B (4.8 [3.6]; p = 0.048) for the AbsCryo compared with TBaseline (5.2 [4.7] and 2.4 [0.9], respectively). Posttreatment, the cryoablation group had no recurrence or metastasis, whereas the resected group showed local recurrence and lung metastasis in 40% of the mice. Postprocedure increase in TIL score of distant tumors was associated with decrease in tumor relapse (p = 0.02). CONCLUSIONS: Cryoablation induced a robust tumor-specific TIL response compared with resection, suggesting an abscopal effect leading to the prevention of cancer recurrence and metastasis.

Late recurrence of Seminoma in the pelvis: A case report.

Recurrence of pure seminoma in atypical lymph node sites, such as the pelvis are rare masses that show clinical signs late in disease progression. We report a case of a 73-year-old male that presented with urinary retention and pain in his left lower extremity with a history of right radical orchiectomy and adjuvant radiation for a stage 1 pure seminoma 30 years prior. CT showed a left pelvic mass concerning for malignancy. Patient subsequently underwent surgical excision of mass that pathology identified as recurrence of pure seminoma. This case report emphasizes etiology of pure seminoma and late, contralateral pelvic recurrence.

Possible clinical implications of prostate capsule thickness and glandular epithelial cell density in benign prostate hyperplasia.

PURPOSE: The negative correlation between BPH-size and incidence of prostate cancer (PCa) is well-documented in the literature, however the exact mechanism is not well-understood. The present study uses histo-anatomical imaging to study prostate volume in correlation to prostate capsule thickness, and glandular epithelial cell density within the peripheral zone (PZ). MATERIALS AND METHODS: Specimens were selected from radical prostatectomies ranging from 20 to 160 mL based on ease of anatomical reconstruction by the slides. A total of 60 patients were selected and underwent quantitative measurements of prostate capsule thickness and glandular epithelial density within the PZ using computer-based imaging software. Pearson's correlation and a stepwise multiple linear regression analysis was conducted to determine the relationship between these measured parameters and the clinical characteristic of these patients. RESULTS: Pearson's correlation analysis revealed a strongly significant, negative correlation between prostate volume and glandular epithelial cell density (r(58)=-0.554, p<0.001), and a strongly significant, positive correlation between prostate volume and average capsule thickness (r(58)=0.462, p<0.001). Results of multiple regression analysis showed that average glandular epithelial cell density added statistically to this prediction (p<0.05). CONCLUSIONS: The results suggest that growth of the transition zone in BPH causes increased fibrosis of the PZ, leading to atrophy and fibrosis of glandular cells. As 80% of PCa originates from the glandular epithelium within the PZ, this observed phenomenon may explain the inverse correlation between BPH and PCa that is well-documented in the literature.

Browning white adipose tissue using adipose stromal cell-targeted resveratrol-loaded nanoparticles for combating obesity.

Enhancing thermogenic energy expenditure via promoting the browning of white adipose tissue (WAT) is a potential therapeutic strategy to manage energy imbalance and the consequent comorbidities associated with excess body weight. Adverse effects and toxicities of currently available methods to induce browning of WAT have retarded exploration of this promising therapeutic approach. Targeted delivery of browning agents to adipose stromal cells (ASCs) in subcutaneous WAT to induce differentiation into beige adipocytes may overcome these barriers. Herein, we report for the first time, ASC-targeted delivery of trans-resveratrol (R), a representative agent, using ligand-coated R-encapsulated nanoparticles (L-Rnano) that selectively bind to glycanation site-deficient decorin receptors on ASCs. After biweekly intravenous administration of L-Rnano to obese C57BL/6 J mice for 5 weeks targeted R delivery significantly induced ASCs differentiation into beige adipocytes, which subsequently resulted in 40% decrease in fat mass, accompanied by improved glucose homeostasis and decreased inflammation. Our results suggest that the ASC-targeted nanoparticle delivery of browning agents could be a transformative technology in combating obesity and its comorbidities with high efficacy and low toxicity.

Cryoablation: A promising non-operative therapy for low-risk breast cancer.

BACKGROUND: The aim of this study was to evaluate the feasibility of cryoablation for early-stage low-risk breast cancer without tumor resection. METHODS: Women diagnosed with ER+, PR+, and HER2-infiltrating ductal carcinomas ≤1.5 cm were treated with cryoablation. The non-surgical procedure used a Visica® 2 Treatment System with ultrasound guidance for ablation of the tumor with a 1 cm margin. Patients were monitored at 6-month intervals by MRI, mammogram, and ultrasound. RESULTS: Twelve patients with unifocal breast cancer were treated with cryoablation for local control without follow-up tumor resection. All patients received adjuvant endocrine therapy, and none had radiation. The median follow-up was 28.5 (range = 4-41) months with 11 patients having at least one six-month follow-up. All imaging modalities showed complete ablation of target zone 11/11 (100%). Four patients (33.3%) have been followed up for ≥ 2 years with no local failure or residual disease. CONCLUSION: Cryoablation of early-stage low-risk (ER+, PR+, and HER2-) breast cancer is a safe alternative to surgery.

Adult Langerhans cell histiocytosis of the central nervous system.

Langerhans cell histiocytosis (LCH), a disorder characterized by aberrant function and proliferation of mononuclear phagocytic cells called Langerhans cells, usually occurs in those <15 years of age. Adult-onset LCH is extremely rare. We present a case of a 35-year-old woman who presented with multiple episodes of confusion, rapidly progressive cognitive decline, and multiple endocrinopathies, including diabetes insipidus. Brain imaging showed a hypothalamic lesion, and biopsy results confirmed the diagnosis of LCH. Given the wide variety of presentations and the multiple differential diagnoses of hypothalamic lesions, it is essential to be aware of this uncommon condition, especially in adults, where it may be underdiagnosed.

Primary Pancreatic Large B-Cell Lymphoma Presenting as Acute Pancreatitis.

Primary pancreatic lymphoma (PPL) is an extremely rare form of extranodal malignant lymphoma. The most common histological subtype of PPL is diffuse large B-cell lymphoma (DLBCL). Clinical and imaging features of PPL may often overlap with pancreatic adenocarcinoma. Therefore, it is very important to obtain a preoperative cytohistology diagnosis of pancreatic tumors to avoid unnecessary surgeries in cases with a diagnosis of PPL. Herein, we report a 71-year-old male who was admitted to our hospital with a diagnosis of acute pancreatitis after he presented with complaints of nausea, vomiting, and epigastric abdominal pain. MRI of the abdomen revealed a pancreatic head mass, and histopathology and immunohistochemical assessment of the pancreatic lesion established the diagnosis of DLBCL. The patient achieved remission after six cycles of rituximab-cyclophosphamide, doxorubicin (hydroxydaunomycin), vincristine (oncovin), prednisolone (R-CHOP) chemotherapy.

Single transverse extended incision for radical neck dissection.

OBJECTIVE: to assess the efficacy of the single transverse extended cervical incision in radical neck dissection. METHOD: we conducted a prospective study, from January 2008 to January 2009, with 18 patients undergoing surgical treatment of malignant tumors of the upper aero-digestive tract. The primary lesion was located in the oral cavity in eight cases, in the oropharynx in three, in the hypopharynx in three, in the larynx in two, in the maxillary sinus, and in one case, the primary injury was hidden. There were 29 neck dissections, eight bilateral and 10 unilateral (26 radical and three selective). Staging revealed nine patients with T4 tumor, one T3, six T2, one T1 and one Tx. Five patients were N0, nine N2b, one N2c and three N3. The average number of dissected lymph nodes was 34.25. We performed the neck dissection through a single incision located in the middle neck, coincident with the skinfold, with a length of about 2 to 3 cm behind the anterior edge of the trapezius muscle and 3 to 4 cm from the midline for the unilateral neck dissections. RESULTS: as complications, there were myocutaneous flap necrosis in one patient with prior radiation therapy, one lymphatic fistula, one dehiscence of the tracheostomy, one cervical abscess, one salivary fistula and one suture dehiscence. CONCLUSIONS: the single extended incision provides adequate exposure of the neck structures, without compromising surgical time, even in bilateral dissections. It does not compromise the resection of all cervical lymph nodes; it has excellent aesthetic and functional results and is easily associated with other approaches to resection of the primary tumor. OBJETIVO: verificar a eficácia da incisão cervical única, transversa e estendida, para o esvaziamento cervical radical. MÉTODO: estudo prospectivo, de janeiro de 2008 a janeiro de 2009, de 18 pacientes submetidos a tratamento cirúrgico de tumores malignos da via aero-digestiva superior. A lesão primária se situava na cavidade oral em oito casos, na orofaringe em três, no seio piriforme em três, na laringe em dois, no seio maxilar em um e em um caso a lesão primária era oculta. Houve 29 esvaziamentos, sendo oito bilaterais e 10 unilaterais (26 radicais e três seletivos). O estadiamento revelou nove pacientes com tumor T4, um T3, seis T2, um T1 e um Tx. Cinco pacientes eram N0, nove N2b, um N2c e três N3. A média de linfonodos dissecados foi de 34,25. O esvaziamento cervical foi realizado por meio de uma única incisão localizada no terço médio do pescoço, coincidente com dobra cutânea, com extensão de cerca de 2 a 3 cm para trás da borda anterior do músculo trapézio e 3 a 4 cm da linha média para os esvaziamentos cervicais unilaterais. RESULTADOS: como complicações houve necrose de retalho miocutâneo em um paciente com radioterapia prévia, uma fistula linfática, uma deiscência do traqueostoma, um abscesso cervical, uma fístula salivar e uma deiscência de sutura. CONCLUSÕES: a incisão única e estendida proporciona exposição adequada das estruturas do pescoço, sem comprometer o tempo cirúrgico, mesmo em esvaziamentos bilaterais. Não compromete a ressecção de todos os linfonodos cervicais, apresenta excelentes resultados estéticos e funcionais e é facilmente associada com outras abordagens para ressecção do tumor primário.

Comparison of in vivo probe-based confocal laser endomicroscopy with histopathology in lung cancer: A move toward optical biopsy.

BACKGROUND AND OBJECTIVE: The development of novel technologies has increased the yield from transbronchial biopsies while preserving patient safety by guiding biopsies to the area of interest. Other technologies have helped identify pre-cancerous or sessile lesions in the endobronchial space by utilizing interactions between tissue and light at varying wavelengths. Probe-based confocal laser endomicroscopy (pCLE) is a new technology that encompasses the benefits of both guided biopsies and novel optical imaging in one device. This project compares pCLE images to the findings of light microscopy in non-small cell lung cancer (NSCLC). METHODS: Patients who underwent bronchoscopies between July 2012 and January 2013 for evaluation of pulmonary lesions (transbronchial and endobronchial) were recruited. Histopathological images from malignant lesions were compared with the pCLE images obtained from the same area. The microscopic and pCLE images were reviewed side by side with the microscopic findings. RESULTS: Images from pCLE correlate with some histopathological findings. pCLE changes seen in NSCLC consist of mottled elastin, septal studding and disorganization/fragmentation with increased friability. These changes also seem to correlate with degrees of differentiation. CONCLUSIONS: pCLE can identify changes to the elastin composition of the airways and alveoli in lung cancer. These changes correlate with histopathology and may help indicate the presence of malignant changes in vivo.

Tubo gástrico isoperistáltico de grande curvatura gástrica com sutura mecânica no tratamento cirúrgico do câncer de esôfago irressecável / Gastric tube of greater gastric curvature with stapler in surgical treatment of non resectable esophageal cancer

RACIONAL: Frequentemente, o diagnóstico da neoplasia do esôfago é tardio, restando como escolha terapêutica o tratamento paliativo. A transposição de tubo isoperistáltico da grande curvatura gástrica é um dos métodos de eleição que, porém, quando complicado com a deiscência da anastomose, impede a alimentação natural, comprometendo a qualidade de vida. OBJETIVO: Avaliar as complicações da anastomose esofagogástrica cervical com sutura mecânica com o tubo gástrico, em pacientes com câncer de esôfago irressecável. MÉTODO: Vinte e dois pacientes com câncer de esôfago irressecável foram submetidos à transposição do tubo gástrico isoperistáltico. A anastomose com o coto esofágico foi realizada com sutura mecânica circular em nível cervical. Foram avaliadas complicações sistêmicas (cardiopulmonares) e locais (a deiscência e a estenose da anastomose esofagogástrica cervical). RESULTADOS: Dez pacientes (45,5 por cento) apresentaram de uma a três complicações, dos quais seis (27,2 por cento) com complicações sistêmicas: um (4,5 por cento) embolia pulmonar (evoluindo ao óbito), um infarto do miocárdio e quatro (18,2 por cento) com infecção de pulmão (todos com boa evolução com o tratamento clínico. Cinco pacientes tiveram complicações locais: três (13,6 por cento) com deiscência da anastomose e quatro (18,2 por cento) com estenose da anastomose, sendo que dois deles tiveram deiscência prévia. De 20 pacientes avaliados em período de seis a 18 meses, 16 (80 por cento) apresentaram deglutição satisfatória para sólidos e/ou pastosos. CONCLUSÃO: O tubo gástrico isoperistáltico de grande curvatura, com sutura mecânica, parece oferecer melhora significativa da deglutição com qualidade de vida satisfatória e morbimortalidade aceitável.

BACKGROUND: The diagnose of esophageal cancer is in general done clinically late, remaining the palliative treatment the only possibility to improve the quality of life. The isoperistaltic gastric tube transposition may be used, however, if leakage happens, the swallow may be hindered, compromising deglutition. AIM: To evaluate the complications that can happen in the cervical esophagogastric anastomosis done with stapler, in patients with non resectable esophageal cancer. METHOD: Twenty two patients with non resectable esophageal cancer were submitted to an isoperistaltic gastric tube transposition. The esophagogastric anastomosis was made with circular stapler. Systemic and local complications were evaluated. RESULTS: Ten patients (45,5 percent) presented 1 to 3 complications, and in 6 (27,2 percent) of them, systemic ones. There were one (4,5 percent) case of lung embolism (with death), one miocardial infarction and four lung infections (all of them with good clinical evolution). Five had local complications; in three (13,6 percent), anastomotic leakage, and in four (18,2 percent), anastomotic stricture among the ones that had previous leakage. Twenty patients were followed through 11 months, and 16 (80 percent) of them maintained satisfactory swallow to solid and/or semi-solid meals. CONCLUSION: The isoperistaltic gastric tube of greater curvature with stapler suture seems to offer significant improvement on swallow with satisfactory quality of life and acceptable morbi-mortality.