PD-L1 Expression in Different Segments and Histological Types of Ovarian Cancer According to Lymphocytic Infiltrate

Background and Objectives: Ovarian cancer is the leading cause of death among gynecological tumors. PD-1/PD-L1 immunoregulatory mechanism is activated in ovarian cancers. Lymphocyte infiltration is a significant factor that affects its expression. We analyzed the correlation between localization of lymphocytic infiltrate and PD-L1 expression in epithelial ovarian tumors. Materials and Methods: PD-L1 expression was analyzed in 328 subjects, 122 with epithelial ovarian carcinoma, 42 with atypical proliferative tumor, and 164 with benign epithelial ovarian tumor. Expression in central and invasive tumor parts in epithelial ovarian carcinoma was combined with the most pronounced lymphocyte reaction. Immunohistochemical analysis was performed using the tissue microarray and correlated with a set of histopathology parameters. Results: PD-L1 expression was most prominent in epithelial ovarian carcinoma with different levels of expression observed between invasive and central tumor segments. A high level of PD-L1 expression on tumor cells was more frequently present in the invasive than in the central tumor parts (p < 0.001) only in high-grade serous ovarian carcinoma (HGSC). There was no significant correlation between peritumoral lymphocytic infiltrate and PD-L1 expression regardless of tumor segment. In the central tumor parts of HGSC, there was a correlation of intratumoral lymphocytic infiltrate with a higher level of PD-L1 expression (p = 0.003). Conclusions: The most prominent PD-L1 expression was observed in the invasive tumor parts of HGSC. Only the central parts of the HGSC exhibited significant PD-L1 expression in association with considerable intratumoral lymphocytic infiltrate.

BRAFV600E Mutant Allele Frequency (MAF) Influences Melanoma Clinicopathologic Characteristics

Background: Cutaneous melanoma shows high variability regarding clinicopathological presentation, evolution and prognosis. Methods: Next generation sequencing was performed to analyze hotspot mutations in different areas of primary melanomas (MMp) and their paired metastases. Clinicopathological features were evaluated depending on the degree of variation of the BRAFV600E mutant allele frequency (MAF) in MMp. Results: In our cohort of 14 superficial spreading, 10 nodular melanomas and 52 metastases, 17/24 (71%) melanomas had a BRAFV600E mutation and 5/24 (21%) had a NRASQ61 mutation. We observed a high variation of BRAFV600E MAF (H-BRAFV600E) in 7/17 (41%) MMp. The H-BRAFV600E MMp were all located on the trunk, had lower Breslow and mitotic indexes and predominantly, a first nodal metastasis. Regions with spindled tumor cells (Spin) and high lymphocytic infiltrate (HInf) were more frequent in the H-BRAFV600E patients (4/7; 57%), whereas regions with epithelial tumor cells (Epit) and low lymphocytic infiltrate (LInf) were predominant (6/10; 60%) and exclusive in the low BRAFV600E MAF variation tumors (L-BRAFV600E). The H-BRAFV600E/Spin/HInf MMp patients had better prognostic features and nodal first metastasis. Conclusions: The H-BRAFV600E MMp were located on the trunk, had better prognostic characteristics, such as lower Breslow and mitotic indexes as well as high lymphocytic infiltrate.

Current Challenges in Deciphering Sutton Nevi—Literature Review and Personal Experience

Halo nevi, known as leukoderma acquisitum centrifugum, Sutton nevus, leukopigmentary nevus, perinevoid vitiligo, or perinevoid leukoderma, together with vitiligo and melanoma-associated hypopigmentation, belong to the group of dermatoses designated as immunological leukodermas. The etiology and pathogenesis of halo nevi has not been fully elucidated. There are several mechanisms through which a lymphocytic infiltrate can induce tumoral regression. In this review, we aimed to update the knowledge about Sutton nevi starting with the clinical appearance and dermoscopic features, continuing with information regarding conventional microscopy, immunohistochemistry, and the immunological mechanisms responsible for the occurrence of halo nevi. We also included in the article original unpublished results when discussing dermoscopic, pathologic and immunohistochemical results in halo nevi. Sutton nevi are valuable models for studying antitumor reactions that the human body can generate. The slow and effective mechanism against a melanocytic skin tumor can teach us important lessons about both autoimmune diseases and anticancer defenses.

Vulvar Cutaneous Myxoma in a Patient With Carney Complex: Avoiding Pitfalls of Myxoid Lesions of the Vulva

We present the case of a 31-year-old woman who underwent surgical excision for a polypoid, vulvar lesion. Histopathological analysis showed a diffuse myxoid stroma admixed with scant collagen fibrils. Thin-walled and branching blood vessels were prominent, with a mild perivascular lymphocytic infiltrate. Cytologically bland spindle cells with inconspicuous nucleoli were immersed in a loose myxoid stroma. This combination of histopathological features along with multinodularity in the subcutaneous fat raised concern for deep angiomyxoma, a locally destructive neoplasm. Among our differential of myxoid lesions of the vulva, we ultimately favored the diagnosis of vulvar cutaneous myxoma. Upon further investigation, we learned that our patient was indeed known for the Carney complex. We highlight that vulvar cutaneous myxomas arising in the context of the Carney complex pose a significant diagnostic challenge for pathologists and should not be overdiagnosed as aggressive lesions such as deep angiomyxoma or other malignant stromal neoplasms.

Lupus miliaris disseminatus faciei: A report with a new dermoscopy finding

Lupus miliaris disseminatus faciei (LMDF) is a rare inflammatory disorder characterized by asymptomatic papular lesions mainly over the central part of the face, common in young adults and with a spontaneously resolving course. Its exact etiology remains unknown, its treatment is problematic, and there is a lack of controlled studies on LMDF. Histopathology shows dermal epithelioid granulomas with central necrosis and surrounding lymphocytic infiltrate with multinucleate giant cells. Dermoscopic findings published show discrete focal orangish structureless areas located around follicular openings with whitish keratotic plugs. Herein, we report a case of LMDF with dermoscopy showing stellate scar signs and structureless white areas.

Hypothalamitis: A Novel Autoimmune Endocrine Disease. A Literature Review and Case Report

Context The relationship between the endocrine system and autoimmunity has been recognized for a long time and one of the best examples of autoimmune endocrine disease is autoimmune hypophysitis. A better understanding of autoimmune mechanisms and radiological, biochemical, and immunological developments has given rise to the definition of new autoimmune disorders including autoimmunity-related hypothalamic–pituitary disorders. However, whether hypothalamitis may occur as a distinct entity is still a matter of debate. Evidence Acquisition Here we describe a 35-year-old woman with growing suprasellar mass, partial empty sella, central diabetes insipidus, hypopituitarism, and hyperprolactinemia. Evidence Synthesis Histopathologic examination of surgically removed suprasellar mass revealed lymphocytic infiltrate suggestive of an autoimmune disease with hypothalamic involvement. The presence of antihypothalamus antibodies to arginine vasopressin (AVP)-secreting cells (AVPcAb) at high titers and the absence of antipituitary antibodies suggested the diagnosis of isolated hypothalamitis. Some similar conditions have sometimes been reported in the literature but the simultaneous double finding of lymphocytic infiltrate and the presence of AVPcAb so far has never been reported. Conclusions We think that the hypothalamitis can be considered a new isolated autoimmune disease affecting the hypothalamus while the lymphocytic infundibuloneurohypophysitis can be a consequence of hypothalamitis with subsequent autoimmune involvement of the pituitary. To our knowledge this is the first observation of autoimmune hypothalamic involvement with central diabetes insipidus, partial empty sella, antihypothalamic antibodies and hypopituitarism.

Avoid a rash diagnosis: Cytophagic histiocytic panniculitis is a distinct clinical entity

Background: Cytophagic histiocytic panniculitis (CHP) is a rare autoimmune disease that can mimic both lupus panniculitis (LP) and subcutaneous panniculitis-like T cell lymphoma (SPTL). Diagnosis is challenging due to overlapping histologic characteristics of these entities. It has historically been considered a pre-malignant lesion, with few case reports detailing CHP as its own entity.Case Presentation: We describe two cases of panniculitis with histologic features similar to both LP and SPTL. Neither patient had clinical or laboratory features convincing of systemic lupus erythematosus (SLE), which made a diagnosis of LP unlikely; T-cell receptor (TCR) gene rearrangement studies demonstrated a polyclonal lymphocytic infiltrate, suggestive of a non-malignant process. Both patients were diagnosed with CHP and responded well to tacrolimus therapy. Conclusions: CHP is a distinct clinical entity, and the panniculitis need not fall under a diagnosis of LP or SPTL. TCR gene rearrangement studies are an essential part of the evaluation to demonstrate polyclonality of the benign lymphocytic infiltrate. T-cell directed therapy represents a rational approach to treatment and yielded success in these two patients.