Angiogenesis plays a crucial role in melanoma metastasis and progression. In recent years, numerous studies have investigated the prognostic and clinical significance of this phenomenon, and the ...development of molecular techniques has enabled us to achieve a better understanding of angiogenesis in melanoma. Herein, we review the current state of knowledge regarding angiogenesis in melanoma, including the pathophysiological, histological and immunohistochemical aspects of this phenomenon. We also review the molecular pathways involved in angiogenesis and the interplay between different components that might be manipulated in the future development of efficient targeted therapies. Recently developed targeted antiangiogenic therapies in clinical trials and included in the treatment of advanced-stage melanoma are also reviewed.
Physician shortages are affecting many communities across the United States and all medical specialties, including pathology. International medical graduates (IMGs) make up a significant proportion ...of US physicians and graduate medical education (GME) trainees, including pathologists. However, noncitizen IMGs continue to face great challenges in entering the US health care workforce.
To show recent and historical data on noncitizen IMGs in pathology GME training and current limitations on them remaining in the US health care workforce.
Compared with applicants who do not need a visa, applicants who need a visa to train in the United States have a greatly reduced chance of matching to a residency program. After completion of residency and fellowship, noncitizen IMGs with J-1 visas face the 2-year home country residence requirement unless they obtain a waiver. H-1B visas facilitate the transition to independent practice but have limited availability. Job announcements for pathologists often do not indicate whether J-1 and H-1B visa holders are considered, which makes the job search process difficult for noncitizen IMGs.
Academic and nonacademic institutions with departments of pathology should increase awareness of the pathologist shortage in the United States and the rules and regulations that limit hiring of non-US IMGs. Such institutions should also actively educate policymakers to promote durable solutions to these issues. One potential solution to these shortages may be to make it easier for noncitizen IMGs to access GME and join and remain in the US physician workforce.
Angiogenesis, the formation of new blood vessels from existing blood vessels, is a complex and highly regulated process that plays a role in a wide variety of physiological and pathological ...processes. In malignancy, angiogenesis is essential for neoplastic cells to acquire the nutrients and oxygen critical for their continued proliferation. Angiogenesis requires a sequence of well-coordinated events mediated by a number of tightly regulated interactions between pro-angiogenic factors and their corresponding receptors expressed on various vascular components (e.g., endothelial cells and pericytes) and stromal components forming the extracellular matrix. In this review, we discuss the functional roles of key growth factors and cytokines known to promote angiogenesis in cutaneous melanoma and key factors implicated in the extracellular matrix remodeling that acts synergistically with angiogenesis to promote tumor progression in melanoma, incorporating some of the most up-to-date basic science knowledge from recently published in vivo and in vitro experimental studies.
Cutaneous angiosarcoma: a current update Shustef, Elina; Kazlouskaya, Viktoryia; Prieto, Victor G ...
Journal of clinical pathology,
11/2017, Letnik:
70, Številka:
11
Journal Article
Recenzirano
Cutaneous angiosarcoma (cAS) is a rare malignant neoplasm with variable clinical presentation. Although a distinct vascular tumour, cAS shares many overlapping histopathological features with other ...vasoformative and epithelioid tumours or 'mimickers'. cAS shows aggressive behaviour and carries a grave prognosis, thus early diagnosis is of paramount importance to achieve the best possible outcomes. Recently, several genetic studies were conducted leading to the identification of novel molecular targets in the treatment of cAS. Herein, we present a comprehensive review of cAS with discussion of its clinical, histopathological and molecular aspects, the differential diagnosis, as well as current therapies including ongoing clinical trials.
Though not required currently for staging, regression is a histopathologic parameter typically reported upon diagnosis of an invasive primary cutaneous melanoma. The studies examining the prognostic ...significance of regression in patient outcome have yielded controversial findings; likely because the definition and assessment of regression have not been consistent, in addition to subjectivity of pathologists' interpretation. Regression is histologically characterized by variable decrease in the number of melanoma cells accompanied by the presence of a host response consisting of dermal fibrosis, inflammatory infiltrate, melanophages, ectatic blood vessels, epidermal attenuation, and/or apoptosis of keratinocytes or melanocytes; the relative extent of these features depends on the stage of the regression. However, the magnitudes to which these individual changes must be present to meet the threshold of histologic regression have not been well defined or agreed upon, and thus, the definition and classification of histologic regression in melanoma varies considerably among institutions and even among individual pathologists. In order to determine the clinical significance of histologic analysis of regression, there is a compelling need for a universal scheme to objectively define and assess histologic regression in primary cutaneous melanoma, so that the biologic and prognostic significance of this process may be completely understood.
In the recent decade, cutting edge molecular and proteomic analysis platforms revolutionized biomarkers discovery in cancers. Melanoma is the prototype with over 51,100 biomarkers discovered and ...investigated thus far. These biomarkers include tissue based tumor cell and tumor microenvironment biomarkers and circulating biomarkers including tumor DNA (cf-DNA), mir-RNA, proteins and metabolites. These biomarkers provide invaluable information for diagnosis, prognosis and play an important role in prediction of treatment response. In this review, we summarize the most recent discoveries in each of these biomarker categories. We will discuss the challenges in their implementation and standardization and conclude with some perspectives in melanoma biomarker research.
Malignant mesothelioma is a locally aggressive malignancy most commonly arising from the pleural and/or peritoneal cavity. Distant cutaneous metastasis is extremely rare. Here, we describe two cases ...of mesothelioma metastatic to the head and neck skin. Case 1: A 64‐year‐old man diagnosed previously with extensive thoracic and abdominal mesothelioma, developed a rapidly growing right upper lip lesion, for which a wedge resection was performed. Case 2: A 77‐year‐old woman with a history of pleural mesothelioma developed a firm, mobile subcutaneous nodule on the right lateral forehead, clinically thought to represent either an epidermal inclusion cyst or a lipoma. A punch biopsy was performed. In both cases, histopathologic evaluation revealed dermal proliferation of epithelioid cells with moderate cytologic atypia and three mitotic figures per mm2 and two mitotic figures per mm2 for Cases 1 and 2, respectively. Immunohistochemical studies revealed the lesional cells to be positive for WT1, mesothelin, D2‐40, CK5/6, while being negative for melanocytic and other keratinocytic markers, supporting a diagnosis of metastatic mesothelioma. Awareness of rare instances of cutaneous metastases from malignant mesothelioma is necessary to avoid possible misdiagnosis and ensure appropriate management.
Immunotherapy targeting the programmed cell death 1 (PD-1) receptor has demonstrated tremendous promise in the treatment of advanced solid tumors. Dermatologic toxicities, however, are an emerging ...consequence of this therapy and have been clearly associated with immune checkpoint blockade antibodies. Distinctive clinical and histologic subtypes of dermatologic toxicity secondary to immunotherapy are emerging and include rare autoimmune bullous reactions (eg, bullous pemphigoid) and lichenoid eruptions. We report three patients who developed lichenoid dermatitis while receiving anti-PD-1 antibody therapy. The mean time to onset of lichenoid dermatologic toxicity was 42 days (range: 1-75 days) from initiation of anti-PD-1 antibody therapy. Lesions most frequently presented on the extremities and trunk as pustules, papules, and plaques. The face was not commonly involved. Of the five skin biopsies examined, all demonstrated dense band-like lymphocytic infiltrate, hyperkeratosis, hypergranulosis, saw-tooth rete ridge pattern, and dyskeratosis. Acanthosis was a feature in all of the skin biopsies, and in one, epidermal hyperplasia was prominent. In several skin biopsies, histologic features supporting a lichenoid drug eruption were present, including parakeratosis, spongiosis, periadnexal/perivascular inflammation, and eosinophils. Furthermore, the histologic features varied in skin biopsy specimens taken from the same patient at different sites, supporting a drug reaction. All patients' skin lesions improved with use of steroids: two were treated with topical steroids and one with systemic steroids. Recognition of the histopathologic patterns of dermatologic toxicities resulting from immune checkpoint blockade therapy will become increasingly important for ensuring appropriate management of dermatologic toxicities and optimal patient care.
Mitotic rate counting is essential in pathologic evaluations in melanoma. The American Joint Committee on Cancer recommends reporting the number of mitotic figures (MFs) in a 1-mm2 area encompassing ...the "hot spot." There is currently no standard procedure for delineating a 1-mm2 region of interest for MF counting on a digital whole slide image (WSI) of melanoma.
To establish a standardized method to enclose a 1-mm2 region of interest for MF counting in melanoma based on WSIs and assess the method's effectiveness.
Whole slide images were visualized using the ImageScope viewer (Aperio). Different monitors and viewing magnifications were explored and the annotation tools provided by ImageScope were evaluated. For validation, we compared mitotic rates obtained from WSIs with our method and those from glass slides with traditional microscopy with 30 melanoma cases.
Of the monitors we examined, a 32-inch monitor with 3840 × 2160 resolution was optimal for counting MFs within a 1-mm2 region of interest in melanoma. When WSIs were viewed in the ImageScope viewer, ×10 to ×20 magnification during screening could efficiently locate a hot spot and ×20 to ×40 magnification during counting could accurately identify MFs. Fixed-shape annotations with 500 × 500-μm squares or circles can precisely and efficiently enclose a 1-mm2 region of interest. Our method on WSIs was able to produce a higher mitotic rate than with glass slides.
Whole slide images may be used to efficiently count MFs. We recommend fixed-shape annotation with 500 × 500-μm squares or circles for routine practice in counting MFs for melanoma.
Deep penetrating nevus (DPN) is an uncommon acquired melanocytic lesion with a distinct histopathological appearance that typically behaves in an indolent manner. The lesion is characterized by a ...symmetrical proliferation of epithelioid to spindled melanocytes associated with abundant melanophages and wedge-shaped extension to the deep reticular dermis and subcutis. Pronounced cytologic atypia and mitotic figures are usually absent, which helps distinguish DPN from melanoma with a deep penetrating growth pattern. Recently, the concept of atypical DPN has been proposed for lesions that demonstrate borderline histomorphologic features and may be associated with lymph node deposits but lack the copy number aberrations typical of melanoma by either fluorescence in situ hybridization or comparative genomic hybridization. While most of these lesions have a favorable clinical course, rare lesions may progress to melanoma. In this review, we summarize the current literature on atypical DPNs with uncertain behavior/metastatic potential and outline the characteristics that distinguish these lesions from conventional DPN and melanoma with DPN-like features.
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