Balloon cell melanoma: a systematic review.

Balloon cell melanoma (BCM) is a rare presentation of malignant melanoma characterized by large, foamy melanocytes lacking pigmentation. This is a comprehensive review of the clinical, dermoscopic, and histological features among BCM cases reported in the literature. A systematic review of all case reports and series published since 1970 was conducted via MEDLINE, Embase, and Web of Science, using "balloon cell melanoma" and synonymous search terms. Our systematic search identified 76 cases (49% male, 51% female) of BCM in the literature. The mean age at presentation was 57.81 years. Prior skin cancer, particularly melanoma (47%), accounted for 58% of pertinent medical history. Prominent clinical exam findings included raised (46%), ulcerated (73%) lesions larger than 1 cm (68%) in the lower extremities (35%). Median Breslow thickness of primary BCM cases was 2.5 mm. Hairpin vessels (75%) and structureless architecture (75%) were predominant on dermoscopy. Notable histopathology included large (47%), vacuolated (58%) cells with foamy cytoplasm (62%) and conspicuous nucleoli (27%). Positive S-100 immunohistochemistry (73%) was most frequently employed to diagnose BCM. We observed 47% primary and 53% metastatic BCM cases. Of metastatic BCMs, balloon cells in the primary lesion were unknown in 48%, devoid in 33%, and present in 20% of cases. All metastases displayed predominant balloon cell morphology. BCM may represent an advanced phase in the progression of malignant melanoma. Improved awareness of BCM characteristics among clinicians may reduce the risk of misdiagnoses.

Muir-Torre Syndrome.

A 64-year-old man was referred to our dermatology clinic with a diagnosis of Muir-Torre syndrome (MTS), he had a history of multiple sebaceous carcinomas and sebaceous adenomas removed over the years. The patient has also had visceral cancer and had undergone a colon resection 17 years before to treat colon cancer and was recently diagnosed with invasive high-grade urothelial carcinoma of the right ureter. In addition, the patient has an extensive family history of cancer; a pedigree was constructed to document this history (Figure 1). Of note is that the patient's mother and father were second cousins. The patient's father was diagnosed with lung cancer at age 57 and died of colon cancer at the age of 72. The patient's mother died of colon cancer at age 74. The patient has three siblings: a sister and two brothers. The sister died of bone cancer at age 42. One brother had a number of cancers including colon, kidney, and skin cancers and died at age 53. His other brother is alive and has a history of colon cancer, kidney cancer, and ureteral cancer. The patient has five children. He has a 40-year-old son who, at the age of 30, was diagnosed with testicular cancer. His daughters are 47, 44, 39, and 34, with no history of malignancy to date. The patient had three maternal aunts, all of whom succumbed to colon cancer, as well as two paternal uncles who died of lung cancer. The patient's maternal grandfather was a smoker and he also died of lung cancer.

Metastatic neuroendocrine tumor of the esophagus with features of medullary thyroid carcinoma.

A 41-year-old female presented with a pedunculated mass in the upper esophagus and bilateral lymphadenopathy. Biopsies suggested a neuroendocrine tumor, possibly carcinoid, and ensuing imaging revealed cervical lymph node metastases. The esophageal mass was removed endoscopically and discovered by pathologists to closely resemble medullary thyroid carcinoma (MTC) on immunohistochemistry staining. Following surgery, further work up demonstrated very high serum calcitonin levels, suggestive of medullary thyroid carcinoma, however the thyroid gland was normal on ultrasound. The patient underwent a neck dissection to remove the lymph node metastases and subsequently her calcitonin levels dropped to 0 ng/mL, indicating remission. It appears that the primary tumor was not in the thyroid, but in the cervical esophagus. The thyroid has appeared normal on multiple ultrasounds without any detectable nodules or masses. This is quite a unique case because this patient presented with a tumor resembling medullary carcinoma of the thyroid that presented as a pedunculated mass in the cervical esophagus. The actual final diagnosis of this mass in the cervical esophagus was neuroendocrine tumor (NET), consistent with a carcinoid tumor, not ectopic MTC. This case report highlights that calcitonin-secreting tumors outside the thyroid should not lead to erroneous recommendations for thyroidectomy.

Feasibility study in teledermatopathology: An examination of the histopathologic features of mycosis fungoides and spongiotic dermatitis.

BACKGROUND: Digital pathology offers numerous advantages, allowing remote information sharing using whole slide imaging (WSI) to digitize an entire glass slide (GS) at high resolution, creating a digital slide (DS). METHODS: In this study, we examine the concordance in diagnoses made on 40 digital slides (DSs) vs traditional GSs in differentiating between spongiotic dermatitis (SD) and patch/plaque-stage mycosis fungoides (MF). RESULTS: Greater interobserver concordance rate in final diagnosis of SD vs MF was observed with the utilization of DS (86.7%) compared with the utilization of GS (80%). Intraobserver concordance rate between the diagnoses rendered by a particular dermatopathologist on GS and DS was 86.7%. For all histopathological criteria, a correlation in the magnitudes of interobserver vs intraobserver discordances suggests that discordance between glass vs digital evaluation of these criteria may be largely expected subjective read variation independent of the media. Discordance in identification of histopathological features did not have a statistically significant link to discordance in diagnosis for 7 out of the 8 features. CONCLUSIONS: The similarity between interobserver and intraobserver discordances suggests that WSI does not introduce additional barriers or variability to accurately identify histopathologic feature and to discriminate between MF and SD beyond interobserver variability.

Sexual side effects of 5-α-reductase inhibitors finasteride and dutasteride: A comprehensive review.

The 5-α-reductase inhibitors finasteride and dutasteride are frequently used in the treatment of androgenetic alopecia and benign prostatichyperplasia. These drugs are effective at reducing levels of dihydrotestosterone, the primary androgen responsible for the pathogenesis of both these conditions. However, finasteride and dutasteride have also been shown to produce an increase in the incidence of sexual dysfunction, namely, impotence, decreased libido, and ejaculation disorder. The purpose of this study is to review the existing medical literature with regard to the sexual side effects of 5-α-reductase inhibitor therapy. This review is an extensive look at the sexual effects of 5-α-reductase inhibitors and compares outcomes for finasteride versus dutasteride in addition to comparing sexualside effects for each of the different dosages prescribed of finasteride and dutasteride.

Comparing whole slide digital images versus traditional glass slides in the detection of common microscopic features seen in dermatitis.

BACKGROUND: The quality and limitations of digital slides are not fully known. We aimed to estimate intrapathologist discrepancy in detecting specific microscopic features on glass slides and digital slides created by scanning at ×20. METHODS: Hematoxylin and eosin and periodic acid-Schiff glass slides were digitized using the Mirax Scan (Carl Zeiss Inc., Germany). Six pathologists assessed 50-71 digital slides. We recorded objective magnification, total time, and detection of the following: Mast cells; eosinophils; plasma cells; pigmented macrophages; melanin in the epidermis; fungal bodies; neutrophils; civatte bodies; parakeratosis; and sebocytes. This process was repeated using the corresponding glass slides after 3 weeks. The diagnosis was not required. RESULTS: The mean time to assess digital slides was 176.77 s and 137.61 s for glass slides (P < 0.001, 99% confidence interval [CI]). The mean objective magnification used to detect features using digital slides was 18.28 and 14.07 for glass slides (P < 0.001, 99.99% CI). Parakeratosis, civatte bodies, pigmented macrophages, melanin in the epidermis, mast cells, eosinophils, plasma cells, and neutrophils, were identified at lower objectives on glass slides (P = 0.023-0.001, 95% CI). Average intraobserver concordance ranged from κ = 0.30 to κ = 0.78. Features with poor to fair average concordance were: Melanin in the epidermis (κ = 0.15-0.58); plasma cells (κ = 0.15-0.49); and neutrophils (κ = 0.12-0.48). Features with moderate average intrapathologist concordance were: parakeratosis (κ = 0.21-0.61); civatte bodies (κ = 0.21-0.71); pigment-laden macrophages (κ = 0.34-0.66); mast cells (κ = 0.29-0.78); and eosinophils (κ = 0.31-0.79). The average intrapathologist concordance was good for sebocytes (κ = 0.51-1.00) and fungal bodies (κ = 0.47-0.76). CONCLUSIONS: Telepathology using digital slides scanned at ×20 is sufficient for detection of histopathologic features routinely encountered in dermatitis cases, though less efficient than glass slides.

Hyperspectral imaging of melanocytic lesions.

Hyperspectral imaging (HSI) allows the identification of objects through the analysis of their unique spectral signatures. Although first developed many years ago for use in terrestrial remote sensing, this technology has more recently been studied for application in the medical field. With preliminary data favoring a role for HSI in distinguishing normal and lesional skin tissues, we sought to investigate the potential use of HSI as a diagnostic aid in the classification of atypical Spitzoid neoplasms, a group of lesions that often leave dermatopathologists bewildered. One hundred and two hematoxylin and eosin-stained tissue samples were divided into 1 of 4 diagnostic categories (Spitz nevus, Spitz nevus with unusual features, atypical Spitzoid neoplasm, and Spitzoid malignant melanoma) and 1 of 2 control groups (benign melanocytic nevus and malignant melanoma). A region of interest was selected from the dermal component of each sample, thereby maximizing the examination of melanocytes. Tissue samples were examined at ×400 magnification using a spectroscopy system interfaced with a light microscope. The absorbance patterns of wavelengths from 385 to 880 nm were measured and then analyzed within and among groups. All tissue groups demonstrated 3 common absorbance spectra at 496, 533, and 838 nm. Each sample group contained at least one absorption point that was unique to that group. The Spitzoid malignant melanoma category had the highest number of total and unique absorption points for any sample group. The data were then clustered into 12 representative spectral classes. Although each of the sample groups contained all 12 spectral vectors, they did so in differing proportions. These preliminary results reveal differences in the spectral signatures of the Spitzoid lesions examined in this study. Further investigation into a role for HSI in classifying atypical Spitzoid neoplasms is encouraged.

Discrepancies in dermatopathology diagnoses: the role of second review policies and dermatopathology fellowship training.

BACKGROUND: Expert consultation and institutional policies mandating second review of pathologic diagnoses in the course of referral have been advocated to optimize patient care. OBJECTIVE: We sought to investigate the rate of diagnostic discrepancies between pathologists with and without dermatopathology fellowship training. METHODS: All available outside pathology reports were reviewed for material sent to the University of Pittsburgh Medical Center Dermatopathology Unit during 1 year. The outside diagnosis was compared with the diagnosis rendered by the referral dermatopathology service. Cases were assigned into 1 of 4 categories: melanocytic neoplasm, nonmelanocytic neoplasm, inflammatory, and other. For each case, the outside pathologist's level of dermatopathology training was noted. Any change in diagnosis resulting in significant alteration in therapy or prognosis, as dictated by the accepted standard of care, was considered a major discrepancy. RESULTS: A total of 405 cases were reviewed. In 51 cases (13%), no preliminary diagnosis was rendered at the outside facility. The referral diagnosis differed from the outside diagnosis in 226 cases (56%), and major discrepancies were identified in 91 cases (22%). Of these 91 cases, 84 were received from outside pathologists who were not dermatopathology trained and 7 were received from pathologists with dermatopathology training. The 91 cases with major discrepancies were categorized as: 36 nonmelanocytic neoplasms (40%), 30 inflammatory (33%), 23 melanocytic neoplasms (25%), and 2 other (2%). LIMITATIONS: This was a retrospective study limited to 2 consultant dermatopathologists at an academic referral center, which typically receives and reviews select cases. CONCLUSION: Dermatopathology fellowship training is associated with a substantial decrease in major diagnostic discrepancies. Pathologists without dermatopathology fellowship training tend to successfully identify those cases for which expert consultation is most useful.

Intravascular schwannoma.

Schwannoma is defined as a benign nerve sheath neoplasm of Schwann cell origin. Cutaneous schwannoma typically manifests along the course of peripheral nerves as a solitary, well-defined, skin-colored nodule within the deep dermis or subcutis of the flexor aspects of the extremities. Schwannoma enlarges slowly and typically follows a benign course, with local recurrence and malignant transformation being exceedingly rare. Although involvement of the vasculature by neurofibroma has been rarely reported, intravascular schwannoma has not been documented to date. We present a unique case of cutaneous schwannoma, as confirmed by histological morphology and immunohistochemistry, within the dermal venous system. Presentation of this case is followed by a discussion of the differential diagnoses of schwannoma, the possible etiologies of the extension of this lesion into the vasculature, and the significance of such a phenomenon.

Molecular bases of cutaneous and uveal melanomas.

Intensive research in recent years has begun to unlock the mysteries surrounding the molecular pathogenesis of melanoma, the deadliest of skin cancers. The high-penetrance, low-frequency susceptibility gene CDKN2A produces tumor suppressor proteins that function in concert with p53 and retinoblastoma protein to thwart melanomagenesis. Aberrant CDKN2A gene products have been implicated in a great many cases of familial cutaneous melanoma. Sporadic cases, on the other hand, often involve constitutive signal transduction along the mitogen-activated protein kinase (MAPK) pathway, with particular focus falling upon mutated RAS and RAF protooncogenes. The proliferative effects of the MAPK pathway may be complemented by the antiapoptotic signals of the PI3K/AKT pathway. After skin, melanoma most commonly affects the eye. Data for the constitutive activation of the MAPK pathway in uveal melanoma exists as well, however, not through mutations of RAS and RAF. Rather, evidence implicates the proto-oncogene GNAQ. In the following discussion, we review the major molecular pathways implicated in both familial and sporadic cutaneous melanomagenesis, the former accounting for approximately 10% of cases. Additionally, we discuss the molecular pathways for which preliminary evidence suggests a role in uveal melanomagenesis.