P16 and HPV status in head and neck sarcomas and sarcomatoid carcinomas.

Human papillomavirus (HPV)-positive oropharyngeal carcinoma is a distinct type of head and neck carcinoma with improved prognosis. p16 immunostaining is often used as a surrogate marker for HPV infection in this particular setting. The aim of this study is to estimate the prevalence of p16 staining and HPV infection in head and neck sarcomatoid carcinomas as well as head and neck sarcomas. 21 sarcomatoid carcinomas and 28 head and neck sarcomas were tested for p16 positivity using immunohistochemical staining, and for high-risk HPV infection using In situ hybridization (ISH). 24 % of sarcomatoid carcinomas and 21 % of sarcomas were positive for p16 staining. All 49 cases were negative for HPV ISH. The results confirm that p16 staining is not specific and may not be associated with HPV infection in non-oropharyngeal head and neck sites. They also indicate that non-oropharyngeal head and neck sarcomatoid carcinomas are not likely to be HPV related.

Muir-Torre syndrome and recent updates on screening guidelines: The link between colorectal tumors and sebaceous adenomas in unusual locations.

BACKGROUND: Muir-Torre syndrome (MTS) is a rare genetic disorder that is caused by mismatch repair (MMR) protein mutations. MTS increases the risk of developing skin and gastrointestinal tumors such as sebaceous adenomas (SAs), sebaceous carcinomas, colorectal cancer, endometrial cancer, and ovarian cancer. The risk of developing these types of tumors varies depending on the involved mutation and the individual's family history risk. CASE PRESENTATION: A 47-year-old male presented with multiple skin lesions on the scalp, face, flank, and back. The examination revealed well-circumscribed, dome-shaped papules with a yellowish appearance with white oily material in the center. Histopathologic examination showed a well-circumscribed sebaceous neoplasm consistent with a mixture of basaloid cells and lobules of bland-appearing mature adipocytes that communicate directly to the surface epithelium. Focal cystic changes and peritumoral lymphocytic infiltrate were noted. Increased mitotic figures were seen in the basaloid cell component. The overall findings were consistent with the diagnosis of SAs. MMR staining showed preserved expression in MLH1 and PMS2 proteins, while MSH2 and MSH6 staining showed loss of protein expression. A screening colonoscopy showed numerous colon and rectal tumors, prompting concerns about the likelihood of MTS. Surgical intervention was pursued for complete resection. Histology revealed a diagnosis of mucinous adenocarcinoma/adenocarcinoma with mucinous features of the colon. The diagnosis of MTS was supported by molecular testing that revealed MSH2 germline mutation. The increased likelihood of MTS was attributed to the occurrence of SAs in unusual locations of the head and neck regions, unlike typical cases. CONCLUSION: MTS is a rare clinical condition that necessitates prompt thorough evaluation and periodic surveillance. When SA is encountered in atypical locations, it is important to consider additional testing supported by immunohistochemical staining, molecular testing, and regular screening to exclude the likelihood of MTS.

Endometrial tumors with yolk sac tumor-like morphologic patterns or immunophenotypes: an expanded appraisal.

Uterine yolk sac tumors have gained increased recognition in recent years. The current study is a multi-faceted examination of yolk sac tumor-like phenotypes in endometrial tumors, based on an analysis of 3 groups of uterine tumors: Group 1: 9 endometrial tumors that had been classified as yolk sac tumor, or as having a yolk sac tumor component, were assessed with a 35-marker immunohistochemical panel, with the goal of defining their immunophenotypic spectrum; Group 2, comprised of 70 endometrial carcinomas of various histotypes, were analyzed for their expression of SALL4, Glypican-3, and AFP, to assess the specificity of these markers for yolk sac tumors relative to endometrial carcinomas; Group 3, comprised of 626 archived cases of endometrial carcinoma/carcinosarcoma, reviewed to define the frequency of yolk sac tumor-like morphology therein. Yolk sac tumor areas in the Group 1 cases were consistently immunoreactive for SALL4 and Glypican-3; variably positive for AFP (89%), Villin (89%), PLAP (78%), 34ßE12 (67%), CAM 5.2 (62.5%), EMA (56%), CD117 (50%), p16 (50%), CDX2 (44%), p53 (44% aberrant), MOC31 (37.5%), CK7 (33%), GATA3 (33%), CK5 (25%), and PAX8 (11%); and were negative for CD30, Napsin A, OCT4, estrogen, androgen, and progesterone receptors. 29 (41%) of the 70 group-2 cases expressed at least one of the 3 markers, and 96% of the positive cases was a high-grade histotype. Glypican-3, SALL4, and AFP were positive in 30, 20, and 2.8% of group-2 cases respectively; however, co-expression of any 2, or all 3 markers was uncommon (<9 and 1.4% of cases respectively). Potential yolk sac tumor-like morphology was identified in 5 (0.8%) of 626 group-3 cases, and three were ultimately deemed to be true yolk sac tumor phenotypes based on their morphologic and immunophenotypic similarity to the group 1 cases. These findings highlight the broad immunophenotypic spectrum of uterine yolk sac tumors, the potential pitfalls associated with using immunophenotypes alone to define yolk sac tumor differentiation in endometrial carcinoma, and the utility and limitations of morphologic assessment to identify yolk sac tumors at this site.

Extra-Ocular Sebaceous Carcinoma in Situ of the Arm of an Elder Male: An Unusual Presentation in an Atypical Location.

Background. Sebaceous carcinoma in situ outside the ocular region is an exceedingly uncommon. It is an intraepidermal neoplasm originating from sebaceous glands limited to the epidermis with no invasion into the underlying dermis or beyond. Although sebaceous carcinoma in situ is predominantly observed in ocular regions, particularly the eyelids, instances of its occurrence in extraocular locations are infrequent, with only a limited number of examples reported in the literature. Case Presentation. A 63-year-old man presented with a left posterior arm lesion. Microscopic examination revealed a proliferation of poorly differentiated atypical neoplastic sebocytes confined to the epidermis with pleomorphic nuclei, prominent nucleoli, and clear cell changes. The neoplastic cells demonstrated positive staining for adipophilin, androgen receptor, epithelial membrane antigen, P63, BerEP4, and keratin 7. Microsatellite instability markers showed preserved nuclear staining for MLH1, PMS2, MSH2, and MSH6. A definitive diagnosis of sebaceous carcinoma in situ was rendered. Discussion. The distinctive histopathologic characteristics typically involve the presence of atypical sebaceous cells confined within the epidermis. Atypical cells often exhibit enlarged nuclei, increased mitotic activity, and prominent nucleoli. A panel of epithelial membrane antigen, adipophilin, and androgen receptors is essential for ensuring an accurate diagnosis. Conclusion. This report underscores the importance of considering sebaceous carcinoma in situ in diagnosis in atypical locations, emphasizing the need for a comprehensive histopathologic examination and immunohistochemical staining panel. This article aims to demonstrate the rarity of sebaceous carcinoma in situ in extraocular sites to broaden our understanding of its diverse clinical presentations.

Unveiling the Uncommon: Gastrointestinal Basidiobolomycosis of the Colon and its Distinctive Splendore-Hoeppli Phenomenon.

BACKGROUND: Basidiobolomycosis is a rare fungal infection caused by Basidiobolus ranarum. CASE PRESENTATION: A 53-year-old man from Saudi Arabia with a known history of diverticulosis presented with severe abdominal pain and diarrhea. A CT scan revealed circumferential wall thickening of the descending and sigmoid colon with surrounding fat stranding, suggesting a diagnosis of complicated diverticulitis. Additional thick fluid was observed around the affected area. Surgical excision was pursued. A gross examination of two received large bowel segments disclosed marked ulcerated mucosa and wall thickening with exudate-covered serosal surfaces and adhesions. Microscopic examination unveiled significant infiltration by eosinophils, polymorphonuclear leukocytes, and granulomatous inflammation. Thin-walled, broad fungal hyphae of Basidiobolus, surrounded by eosinophilic material, were identified. Granulomas displayed abundant multinucleated giant cells and palisading histiocytes around central necrosis or abscess formation. Thin-walled, broad fungal hyphae of Basidiobolus, with sparse septations, are surrounded by a radiating, intensely eosinophilic cuff (Splendore-Hoeppli phenomenon). These hyphae, visible with hematoxylin and eosin staining, were further highlighted with periodic acid-Schiff and Gomori methenamine silver staining. DISCUSSION: Basidiobolomycosis may mimic neoplastic lesions. Histologically, the characteristic features include broad, thin-walled septate hyphae surrounded by eosinophilic material, a finding that is accentuated by the Splendore-Hoeppli phenomenon. Microscopic examination, along with special stains such as periodic acid-Schiff (PAS) and Gomori methenamine silver, is essential for accurate diagnosis. CONCLUSION: Prompt recognition and appropriate antifungal therapy are vital for favorable patient outcomes. This report highlights the distinctive features of Basidiobolomycosis to raise awareness and understanding of this infrequent yet clinically significant fungal infection.

Erythema Multiforme-Like Fixed Drug Eruption During Azathioprine and Hydroxychloroquine Treatment for Systemic Lupus Erythematosus Mimicking Rowell Syndrome: A Rare and Challenging Clinical Scenario.

Background. Fixed drug eruption and Rowell syndrome stand as intriguing entities with overlapping clinical and pathological features. Case Presentation. A 32-year-old female patient presented with a tender and pruritic rash on the left upper chest for 3 days. Clinical examination revealed a flaring rash on the chest, under her left eye, tongue, and lips. The patient had a significant past medical history of systemic lupus erythematous with positive (ANA, Sm, dsDNA, ribosomalP, RNP) antibodies, hypocomplementemia, inflammatory arthritis, discoid lupus, leukopenia, thrombocytopenia, and immune thrombocytopenic purpura, and avascular necrosis affecting both hips and her right knee. At the time of presentation, the patient was on azathioprine 150 mg daily and hydroxychloroquine 200 mg twice daily. Skin biopsy of the left upper chest revealed interface dermatitis with necrotic keratinocytes at the dermal-epidermal junction. Superficial and, in some areas, deep perivascular and peri adnexal lymphocytic infiltrates were observed, accompanied by eosinophils. CD123 staining highlighted 16% of the inflammatory cells. Direct Immunofluorescence for IgG, IgA, IgM, C3, and fibrinogen revealed positive linear basement membrane staining for IgG and fibrinogen, with no significant staining for the remaining immunoreactants. Considering the patient's history of medicine usage, and negative SS-A and SS-B antibody, a fixed drug eruption was favored. Discussion. This article discusses the clinical presentations, pathophysiological mechanisms, and diagnostic criteria for fixed drug eruption and Rowell syndrome. Conclusion. Awareness of the distinct clinical and histopathologic features of fixed drug eruption and Rowell syndrome, particularly when sharing cutaneous manifestations, underscores the importance of a comprehensive diagnostic approach and laboratory testing.

Delayed Diagnosis of SMARCA4-Deficient Undifferentiated Tumor in a Heavy Smoker Male Patient: Discovered Through Bone Sampling, with Extensive Distant Metastases and Concurrent Granulomatous Disease, Leading to Patient Fatality.

Background. SMARCA4-deficient undifferentiated tumors are rare and pose a diagnostic challenge. This study delves into the intricate diagnostic terrain of SMARCA4-deficient undifferentiated tumors, providing insights into their diverse clinical presentations and diagnostic approaches. Case Presentation. A 69-year-old heavy-smoker man with adalimumab-treated rheumatoid arthritis presented with multiple lesions. A CT scan revealed a spiculated lung mass, enlarged mediastinal lymph nodes, and hepatic lesions. A whole-body FDG-PET/CT scan revealed heterogeneous hypermetabolic lesions in the lung, liver, and bone. Initial two core needle liver biopsies and a left upper lobe lung wedge resection initially indicated steatohepatitis and granulomatous formation with no evidence of malignancy. Several months later, the patient returned with left-sided flank pain and significant weight loss. CT scan identified a thigh mass, adrenal lesion, and extensive multiple skeletal lesions. A biopsy of the thigh mass revealed an extensively necrotic, epithelioid-to-spindled cell neoplasm with positive staining for pan keratin, focal staining for CD56, and a loss of nuclear expression of SMARCA4. A final diagnosis of SMARCA4-deficient undifferentiated tumor was rendered. Unfortunately, the patient's condition deteriorated, and he died a few weeks after receiving the final diagnosis. Conclusion. SMARCA4-deficient undifferentiated tumors have emerged as recent subjects of medical study, distinguished by their unique morphology and SMARCA4-deficient immunohistochemistry. These tumors present diverse clinical manifestations, affecting multiple organ systems. This report underscores the diagnostic complexities associated with complex clinical presentation and highlights the importance of multidisciplinary collaboration in addressing challenging clinical scenarios, particularly among heavy smoker male patients and intricate radiological presentations.

Myxoid neurofibroma masquerading as lymphatic-venous malformation and poses a diagnostic challenge on fine needle aspiration biopsy.

BACKGROUND: Myxoid neurofibromas (NF) are uncommon, benign spindle cell tumors that originate from peripheral nerve sheaths, often posing a diagnostic challenge due to their hypocellularity on cytology specimens. Distinguishing myxoid spindle cell lesions can be challenging, given the broad range of potential differential diagnoses. CASE PRESENTATION: A 26-year-old female with a past medical history of embolized inguinal, flank, and retroperitoneal venolymphatic malformation presented with a left pelvic pain causing significant disability. CT scan showed an extensive 8.7 cm × 6.6 cm retroperitoneal mass. FNA was performed and alcohol-fixed papanicolaou-stained smears showed a hypocellular specimen with loosely arranged clusters of bland spindle cell proliferation in the background of a mucoid matrix. Spindle cells showed scant cytoplasm and elongated oval-shaped regular nuclei. Prominent nucleoli were not seen. An excisional biopsy revealed a bland spindle cell proliferation in a myxoid background associated with shredded collagen bundles. Immunohistochemical staining showed diffuse positivity for S100 and CD34. Based on the overall findings, a definitive diagnosis of myxoid neurofibroma was rendered. DISCUSSION: Cytological features of myxoid neurofibroma include the presence of hypocellular spindle-shaped cells arranged in small, loosely organized groups within a myxoid matrix background. Cells exhibit scant cytoplasm with regular oval and elongated nuclei. Nucleoli are typically not identified. The differential diagnosis includes myxoid neurofibroma, myxoma, myxoid liposarcoma, myxoid chondrosarcoma, myxoid dermatofibrosarcoma protuberans, low-grade fibromyxoid sarcoma, and low-grade myxo-fibrosarcoma. CONCLUSION: We aim to highlight the importance of considering myxoid neurofibroma in the differential diagnosis of hypocellular myxoid spindle cell lesions encountered on fine-needle aspiration cytology.

Pulmonary Langerhans Cell Histiocytosis Post-Hodgkin Lymphoma Completely Resolved With Vinblastine in a Heavy Smoker: Coincidence or Causation?

The association among Langerhans cell histiocytosis, hematolymphoid malignancies, and heavy smoking has been addressed in medical literature to identify a possible potential link. Such occurrence can pose diagnostic challenges, as well as important clinical implications for disease progression and treatment approaches. We present pulmonary Langerhans cell histiocytosis instance in a 35-year-old male patient, with a 34-pack-year smoking history and nodular sclerosing Hodgkin lymphoma stage IIB who developed multiple bilateral lung nodules. The patient completed 6 cycles of doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine chemotherapy and radiotherapy 2 years earlier. CT chest scans revealed numerous micronodules scattered randomly throughout the upper and lower left lung lobes. Subsequent wedge resection exhibited cellular proliferation with grooved nuclei, eosinophilic cytoplasm, and surrounding inflammatory components. Immunohistochemical staining showed positive staining for S100 and CD1a confirming a diagnosis of pulmonary Langerhans cell histiocytosis. The patient responded to a 6-week treatment with vinblastine and prednisolone. A subsequent CT scan of the lungs revealed complete resolution after 3 years. This report underscores the importance of identifying pulmonary Langerhans cell histiocytosis in heavy smokers with Hodgkin lymphoma presenting with multiple nodular pulmonary lesions. For patients with Hodgkin lymphoma and a possible genetic predisposition, smoking may contribute to the overt development of pulmonary Langerhans cell histiocytosis. Therefore, smoking cessation and careful follow-up examinations are required. Further research is recommended to elucidate the underlying mechanisms of this intriguing association.

Fumarate Hydratase-Deficient Abdominal Wall Leiomyoma Presenting a Decade Post-Fumarate Hydratase-Deficient Uterine Leiomyoma Excision: An Incidental or Syndromic Association?

Background. The occurrence of fumarate hydratase-deficient leiomyoma of the abdominal wall is exceptionally rare. Case Presentation. A 50-year-old female patient with a past medical history of fumarate hydratase-deficient uterine leiomyoma presented with a left lower quadrant abdominal mass that has been present for the past 2 years. An ultrasound revealed a 3.5 cm oval hypoechoic mass. A subsequent CT scan showed a 3.5 cm hyperdense mass within the left internal oblique musculature. No family history is noted. A biopsy of the mass exhibited bundles of spindle cell neoplasm exhibiting bizarre ovoid nuclei and eosinophilic cytoplasm. No evidence of mitotic figures or tumor necrosis was noted. Immunohistochemical staining showed positive staining for desmin and smooth muscle actin (SMA), but negative staining for MART-1, S100, and CD34. Lesional cells showed expression of 2-succinocysteine and loss of fumarate hydratase expression. A diagnosis of fumarate hydratase-deficient leiomyoma was rendered. Conclusion. This report reinforces the importance of considering genetic testing for fumarate hydratase mutations in the evaluation of extra-uterine leiomyomatous lesions. Comprehensive follow-up and clinical screening in individuals with new lesions and a known history of fumarate hydratase-deficient neoplasms is mandatory. Recent recommendations support the integration of morphology-based evaluation along with immunohistochemical staining and genetic testing as a part of the standard evaluation for all uterine leiomyomas.

Malignant Para-Testicular Mesothelioma: A Rare Presentation in the Tunica Vaginalis of an Elderly Male With No Prior Asbestos Exposure.

Malignant mesothelioma of the tunica vaginalis is an extremely rare and aggressive tumor that is frequently encountered in elderly patients. The diagnosis of malignant mesothelioma of the tunica vaginalis poses a diagnostic challenge due to its infrequency and nonspecific clinical presentation. Histopathological examination and immunohistochemical staining are essential in differentiating this tumor from other para-testicular masses and establishing a definitive diagnosis. Early detection and comprehensive treatment planning are crucial for improving the prognosis and overall outcomes for patients with this rare malignancy. We present a report of malignant mesothelioma of the tunica vaginalis in a 78-year-old male patient with no history of asbestos exposure who presented with a large infiltrative left para-testicular mass. Histopathological examination revealed a biphasic proliferation composed of epithelioid and spindle cells with infiltrative features, foci of necrosis, and increased mitotic figures. Immunohistochemical staining exhibited positive staining for WT1, D2-40, and calretinin, supporting the mesothelial origin of the tumor. Notably, BerEP4 staining was negative, arguing against carcinoma. Immunostaining for keratin 5 was positive, supporting the mesothelial differentiation. The Ki67 proliferation index was high. The differential diagnosis included adenomatoid tumors, germ cell tumors, and pleomorphic sarcoma. We aim to discuss the clinical presentation, diagnostic approach, and therapeutic approaches of this rare entity.

Lipoprotein Glomerulopathy With Complete Resolution With Fenofibrate: Report of First Case From Pakistan.

Background: Lipoprotein glomerulopathy is an infrequent glomerular disorder that culminates in nephrotic syndrome and often progresses to kidney failure. Whereas most patients have been reported in Japan and China, limited reports have been documented outside these regions. This patient represents the first report of lipoprotein glomerulopathy in Pakistan. Case Presentation: A 25-year-old male patient, hypertensive for 2 years, presented with progressive body edema, frothy urine, and fatigue. Examination revealed elevated blood pressure, bilateral pedal edema, and positive shifting dullness. Laboratory results showed significant proteinuria and elevated cholesterol and triglyceride levels. Renal biopsy revealed enlarged glomeruli with a dilated capillary lumen filled with pale-staining mesh-like material "lipoprotein thrombi." Mild tubular atrophy and interstitial inflammation were observed. No interstitial fibrosis was evident. Electron microscopy detailed the lipoprotein thrombi with lipid granules and vacuoles of various sizes. A diagnosis of lipoprotein glomerulopathy was rendered. Treatment with fenofibrate, rosuvastatin, and captopril led to notable improvements in symptoms, blood pressure, and lipid levels during a 6-month follow-up. Subsequent biopsy showed complete resolution of the lipoprotein thrombi and a significant reduction in subendothelial granular densities. However, the flocculent subendothelial material persisted to some extent despite the complete resolution of lipoprotein thrombi. Conclusion: This report underscores the rarity of lipoprotein glomerulopathy in Pakistan and contributes valuable insights into its histopathologic features and global epidemiology. This unique instance aims to raise awareness among healthcare professionals, aiding in improved recognition of this rare entity. The favorable response to fenofibrate treatment underscores its effectiveness in managing lipoprotein glomerulopathy.

Pseudoangiomatous Spindle Cell Lipoma: A Rare and Distinct Pattern of Lipomatous Tumors.

Pseudoangiomatous spindle cell lipoma is a rare pattern within the spindle cell lipoma spectrum that exhibits a remarkable histological pattern characterized by its resemblance to vascular lesions, creating a pseudoangiomatous appearance. Approximately 20 to 30 reports have been described in the literature. In this context, we present an intriguing report of pseudoangiomatous spindle cell lipoma showcasing a unique low-fat pseudo angiomatous pattern in a 61-year-old male patient presented with a 6-cm subcutaneous mass on his right arm, which was thoroughly investigated and subsequently excised. Microscopic examination revealed bland spindle cells infiltrates within a fibromyxoid stroma. Notably, the tumor exhibited distinctive branching and dilated vascular-like spaces that formed pseudopapillary (villiform) projections. Interestingly, the tumor displayed certain regions featuring mature adipose tissue components, alongside hyalinized blood vessels. No necrosis, atypical spindle cells, increased mitotic activity, or pleomorphic lipoblasts were observed. The immunohistochemical evaluation demonstrated diffuse positive staining for CD34 and negative staining for STAT6. This report of a low-fat pattern of pseudoangiomatous spindle cell lipoma underscores the importance of recognizing and characterizing rare entity subtype for accurate diagnosis and appropriate management. This report contributes to the expanding understanding of the diverse presentations of pseudo angiomatous spindle cell lipomas and underscores the significance of comprehensive histopathological assessment.

African American Females Are Less Metabolically Flexible Compared with Caucasian American Females following a Single High-Fat Meal: A Pilot Study.

The relationship between metabolic flexibility (MF) and components of metabolic disease has not been well-studied among African American (AA) females and may play a role in the higher incidence of chronic disease among them compared with Caucasian American (CA) females. This pilot study aimed to compare the metabolic response of AA and CA females after a high-fat meal. Eleven AA (25.6 (5.6) y, 27.2 (6.0) kg/m2, 27.5 (9.7) % body fat) and twelve CA (26.5 (1.5) y, 25.7 (5.3) kg/m2, 25.0 (7.4) % body fat) women free of cardiovascular and metabolic disease and underwent a high-fat meal challenge (55.9% fat). Lipid oxidation, insulin, glucose, and interleukin (IL)-8 were measured fasted, 2 and 4 h postprandial. AA females had a significantly lower increase in lipid oxidation from baseline to 2 h postprandial (p = 0.022), and trended lower at 4 h postprandial (p = 0.081) compared with CA females, indicating worse MF. No group differences in insulin, glucose or HOMA-IR were detected. IL-8 was significantly higher in AA females compared with CA females at 2 and 4 h postprandial (p = 0.016 and p = 0.015, respectively). These findings provide evidence of metabolic and inflammatory disparities among AA females compared with CA females that could serve as a predictor of chronic disease in individuals with a disproportionately higher risk of development.

Targeting Plk1 Sensitizes Pancreatic Cancer to Immune Checkpoint Therapy.

Polo-like kinase 1 (Plk1) plays an important role in cell-cycle regulation. Recent work has suggested that Plk1 could be a biomarker of gemcitabine response in pancreatic ductal adenocarcinoma (PDAC). Although targeting Plk1 to treat PDAC has been attempted in clinical trials, the results were not promising, and the mechanisms of resistance to Plk1 inhibition is poorly understood. In addition, the role of Plk1 in PDAC progression requires further elucidation. Here, we showed that Plk1 was associated with poor outcomes in patients with PDAC. In an inducible transgenic mouse line with specific expression of Plk1 in the pancreas, Plk1 overexpression significantly inhibited caerulein-induced acute pancreatitis and delayed development of acinar-to-ductal metaplasia and pancreatic intraepithelial neoplasia. Bioinformatics analyses identified the regulatory networks in which Plk1 is involved in PDAC disease progression, including multiple inflammation-related pathways. Unexpectedly, inhibition or depletion of Plk1 resulted in upregulation of PD-L1 via activation of the NF-κB pathway. Mechanistically, Plk1-mediated phosphorylation of RB at S758 inhibited the translocation of NF-κB to nucleus, inactivating the pathway. Inhibition of Plk1 sensitized PDAC to immune checkpoint blockade therapy through activation of an antitumor immune response. Together, Plk1 suppresses PDAC progression and inhibits NF-κB activity, and targeting Plk1 can potentiate the efficacy of immunotherapy in PDAC. SIGNIFICANCE: Inhibition of Plk1 induces upregulation of PD-L1 expression in pancreatic ductal adenocarcinoma, stimulating antitumor immunity and sensitizing tumors to immunotherapy.

High-fat meal increases peripheral blood mononuclear cell pro-inflammatory cytokine expression in African-American women.

African-American (AA) women have elevated predominance of inflammatory diseases concurrent with local inflammation resulting in compromised metabolic function. The purpose of the study was 2-fold: 1) to examine the gene and protein expression of pro- and anti-inflammatory cytokine secretion by peripheral blood mononuclear cells (PBMC) obtained from AA and Caucasian-American (CA) women in response to an acute high-fat meal; and 2) to explore the influence of race (AA vs. CA) on PBMC reactivity. Ten AA and 11 CA women consumed a high-fat meal with baseline and 4 h postprandial venous blood draws. PBMCs were incubated for 3 h then messenger RNA expression and supernatant protein concentration was used to examine inflammatory profiles. All women had a postprandial increase in interleukin (IL)-8 gene expression, IL-8 protein concentration, and tumor necrosis factor alpha (TNF-α) protein concentration (P < 0.05). AA women had a postprandial increase in IL-6, IL-8, and TNF-α protein concentration (P < 0.05). AA women had higher postprandial IL-1ß protein concentration and IL-8 gene expression compared with CA women (P < 0.05). Our data uncovers the specific impact of race and time on pro-inflammatory PBMC (IL-1ß, IL-6, IL-8, and TNF-α) expression profiles in response to an acute high-fat meal challenge. Novelty: African Americans have higher predominance of inflammatory disease. We explored the potential race impact on peripheral blood mononuclear cell reactivity in response to a meal. A pro-inflammatory response to an acute high-fat meal with race impact was observed possibly contributing to health disparities impacting African-American women.