Artificial Intelligence in Melanoma Dermatopathology: A Review of Literature.

ABSTRACT: Pathology serves as a promising field to integrate artificial intelligence into clinical practice as a powerful screening tool. Melanoma is a common skin cancer with high mortality and morbidity, requiring timely and accurate histopathologic diagnosis. This review explores applications of artificial intelligence in melanoma dermatopathology, including differential diagnostics, prognosis prediction, and personalized medicine decision-making.

A comparative study of histopathologic features in alopecia areata and pattern hair loss.

BACKGROUND: When peribulbar infiltrates are absent, other histopathologic findings are necessary to distinguish alopecia areata (AA) from pattern hair loss (PHL). The purpose of this study is to determine which histopathologic features are most useful for differentiation. METHODS: A retrospective slide review was conducted of AA and PHL scalp biopsy specimens from 2014 to 2019 at a tertiary referral center. RESULTS: Ninety-six cases were retrieved, of which 38 were AA. Peribulbar infiltrates were identified in 24 AA (63.2%) cases. A catagen/telogen shift was observed more frequently in AA than PHL (25 cases, 65.5% vs. 10 cases, 17.2%; p ≤ 0.0001). Lymphocytes (4 cases, 10.5% vs. 1 case, 1.7%; p = 0.058) and melanin (25 cases, 65.8% vs. 5 cases, 8.6%; p ≤ 0.0001) in fibrous tracts were more common in AA. Apoptotic bodies within vellus hairs were more frequently identified in AA (32 cases, 84.2% vs. 37 cases, 63.8%; p = 0.030). Small dystrophic follicles were also more common in AA (16 cases, 42.1% vs. 1 case, 1.7%; p < 0.0001). CONCLUSIONS: Common features of AA other than peribulbar infiltrates include a catagen/telogen shift, melanin in fibrous tracts, and small dystrophic follicles. Practitioners should consider these features when distinguishing AA from PHL in specimens without peribulbar infiltrates. The retrospective design limits our ability to exclude multifactorial alopecia, such as telogen effluvium.

Histologic Screening of Malignant Melanoma, Spitz, Dermal and Junctional Melanocytic Nevi Using a Deep Learning Model.

OBJECTIVE: The integration of an artificial intelligence tool into pathologists' workflow may lead to a more accurate and timely diagnosis of melanocytic lesions, directly patient care. The objective of this study was to create and evaluate the performance of such a model in achieving clinical-grade diagnoses of Spitz nevi, dermal and junctional melanocytic nevi, and melanomas. METHODS: We created a beginner-level training environment by teaching our algorithm to perform cytologic inferences on 136,216 manually annotated tiles of hematoxylin and eosin-stained slides consisting of unequivocal melanocytic nevi, Spitz nevi, and invasive melanoma cases. We sequentially trained and tested our network to provide a final diagnosis-classification on 39 cases in total. Positive predictive value (precision) and sensitivity (recall) were used to measure our performance. RESULTS: The tile-classification algorithm predicted the 136,216 irrelevant, melanoma, melanocytic nevi, and Spitz nevi tiles at sensitivities of 96%, 93%, 94% and 73%, respectively. The final trained model was able to correctly classify and predict the correct diagnosis in 85.7% of unseen cases (n = 28), reporting at or near screening-level performances for precision and recall of melanoma (76.2%, 100.0%), melanocytic nevi (100.0%, 75.0%), and Spitz nevi (100.0%, 75.0%). CONCLUSIONS: Our pilot study proves that convolutional networks trained on cellular morphology to classify melanocytic proliferations can be used as a powerful tool to assist pathologists in screening for melanoma versus other benign lesions.

Fusion partners of NTRK3 affect subcellular localization of the fusion kinase and cytomorphology of melanocytes.

A subset of Spitz tumors harbor fusions of NTRK3 with ETV6, MYO5A, and MYH9. We evaluated a series of 22 melanocytic tumors in which an NTRK3 fusion was identified as part of the diagnostic workup. Tumors in which NTRK3 was fused to ETV6 occurred in younger patients were predominantly composed of epithelioid melanocytes and were classified by their histopathologic features as Spitz tumors. In contrast, those in which NTRK3 was fused to MYO5A were predominantly composed of spindled melanocytes arrayed in fascicles with neuroid features such as pseudo-Verocay bodies. To further investigate the effects of the fusion kinases ETV6-NTRK3 and MYO5A-NTRK3 in melanocytes, we expressed them in immortalized melanocytes and determined their subcellular localization by immunofluorescence. ETV6-NTRK3 was localized to the nucleus and diffusely within the cytoplasm and caused melanocytes to adopt an epithelioid cytomorphology. In contrast, MYO5A-NTRK3, appeared excluded from the nucleus of melanocytes, was localized to dendrites, and resulted in a highly dendritic cytomorphology. Our findings indicate that ETV6-NTRK3 and MYO5A-NTRK3 have distinct subcellular localizations and effects on cellular morphology.

Monitoring Response to Platelet-Rich Plasma in Patients with Alopecia Areata with Optical Coherence Tomography: A Case Series.

Alopecia areata (AA) is an autoimmune hair loss condition that is difficult to treat and frequently disruptive to the psychosocial well-being of patients. Platelet-rich plasma (PRP) is an innovative therapy that provides concentrated GFs that impart anti-inflammatory effects. Optical coherence tomography (OCT) is a noninvasive imaging modality with the potential for providing quantitative monitoring of AA response to PRP. Our objective is to share our experience using OCT to monitor the therapeutic progress of patients with AA treated with PRP. Two patients with patchy AA and one with alopecia universalis were treated with PRP three times at 6-week intervals as part of a larger clinical trial. Patients were followed from baseline to week 24 with OCT imaging. OCT demonstrates an increase in hair density associated with improvement in inflammation at week 24. Conversely, the patient with alopecia universalis did not experience any significant change in follicular activity. This case series exemplifies the potential of PRP in inflammatory regulation as well as hair regrowth in patchy AA, whereas there is no notable advantage in alopecia universalis. Our findings add evidence on the possible value of OCT in quantitatively assessing hair growth progress throughout a treatment course.

Hemangioma-related syndromes.

PURPOSE OF REVIEW: There is a growing understanding of complications and anomalies associated with infantile hemangiomas. The current review will discuss recent clinical advances in syndromes associated with segmental hemangiomas, including PHACE and LUMBAR syndrome. In addition, the importance of recognizing visceral hemangiomatosis is highlighted. RECENT FINDINGS: Ongoing longitudinal studies of PHACE and LUMBAR syndromes associated with segmental infantile hemangiomas have led to improved diagnosis and recommendations for screening for associated anomalies. Characterization of a growing spectrum of associated anomalies as well as better classification of at-risk patients will improve diagnosis and outcomes. In addition, visceral hemangiomatosis recognition and understanding of the potential association with consumptive hypothyroidism will improve initiation of appropriate screening. SUMMARY: Clinicians should be aware of infantile hemangiomas associated with potential syndromic complications and recognize the need to initiate appropriate work-up. Segmental hemangiomas of the head and neck region may indicate a risk of PHACE syndrome and associated developmental anomalies. Although LUMBAR syndrome is the association of lower body segmental hemangioma with developmental anomalies. Visceral hemangiomas most commonly affect the liver and may be associated with complications such as consumptive hypothyroidism and heart failure.

Feature characterization of scarring and non-scarring types of alopecia by multiphoton microscopy.

OBJECTIVES: Non-invasive visualization of hair follicles is important for proper diagnosis and management of alopecia; however, histological assessment remains the gold standard. Laser imaging technologies have made possible noninvasive in vivo evaluation of skin and hair follicle. The aim of this study was to evaluate the ability of multiphoton microscopy (MPM) to non-invasively identify morphological features that can distinguish scarring from non-scarring alopecia. METHODS: MPM images were obtained from areas on the scalp affected by alopecia. Investigators blinded to the diagnosis analyzed hair follicle and shaft sizes. Patients were recruited and imaged at the UC Irvine Health Medical Center and the University of California, Irvine Beckman Laser Institute. Patients with androgenetic alopecia (AGA) and alopecia areata (AA), and scarring alopecia, in particular frontal fibrosing alopecia (FFA) were recruited and imaged from July 2016 to July 2017. RESULTS: We imaged 5 normal scalp subjects and 12 patients affected by non-scarring (7 subjects) and scarring (5 subjects) alopecia. In normal and non-scarring alopecia patients, MPM identified presence of sebaceous glands associated with hair follicles. MPM images of scarring alopecia were characterized by the presence of inflammatory cells surrounding hair follicles. Measurements of hair follicle diameter sizes were found to be significantly smaller in scarring alopecia patients compared to normal (P < 0.001) and compared to non-scarring alopecia patients (P = 0.046); non-scarring hair follicles were also significantly smaller than normal hair follicles (P = 0.043). CONCLUSIONS: This study shows that MPM imaging can non-invasively identify morphological features that distinguish scarring from non-scarring alopecia. Further studies are needed to validate this technique and evaluate its potential to be used as an aid for guiding treatment. Lasers Surg. Med. 51:95-103, 2019. © 2018 Wiley Periodicals, Inc.

Radiofrequency Therapy and Noncosmetic Cutaneous Conditions.

BACKGROUND: The need for noninvasive methods in treatment of cutaneous disease has continued to evolve exponentially. Amidst the search for technologies, radiofrequency (RF) has proven efficacious in numerous skin disease processes. Although RF is well known for its cosmetic utility, its mechanism is valued in the treatment of many noncosmetic cutaneous conditions of various etiologies. OBJECTIVE: To identify and describe studies in which RF was used to treat noncosmetic skin conditions and to explore the potential of this modality for further application in dermatologic diseases. MATERIALS AND METHODS: The PubMed database was used to find relevant articles. RESULTS: This search strategy yielded 54 articles that met the eligibility criteria. Noncosmetic indications discussed in these articles include varicose veins (n = 10,550), lymphangioma circumscriptum (n = 72), cutaneous neoplasms (n = 42), cutaneous leishmaniasis (n = 743), acne and acne scarring (n = 158), non-acne scarring (n = 43), primary axillary hyperhidrosis (n = 76), and acute and chronic wounds (n = 94). CONCLUSION: Treatment with RF is an effective, generally noninvasive modality with a relatively short postprocedure recovery time and little potential for severe adverse effects in the treatment of several cutaneous conditions. Further clinical studies would prove useful to assess the efficacy and cost-effectiveness of this treatment.

Nuclear and cytoplasmic features in the diagnosis of Clark's nevi.

BACKGROUND: Interpretation of Clark's nevi has generated debate over the years; although criteria have been proposed for grading morphological features of melanocytes, there is still confusion and variability in the assessment of these lesions. METHODS: This is a retrospective observational study conducted on 100 Clark's nevi and 84 melanomas. A single expert dermatopathologist evaluated all blinded and randomized photomicrographs of both the Clark's nevi and melanomas for the presence of 14 cytologic features. Subsequently, a multivariate model was used to obtain sensitivity and specificity. RESULTS: Clark's nevi showed a significantly higher frequency of absent-or-inconspicuous nucleoli over melanoma, whereas mitotic figures, pleomorphism, notching, multiple nucleoli, peppered moth nuclear pattern, flattened adjacent nuclei, prominent nucleoli and vesicular nucleus with rounded nucleoli were found significantly higher in frequency in melanomas. CONCLUSION: Our data suggest that nuclear alterations are of value in the differentiation of atypical nevi from melanoma.

Diagnostic Criteria in Intraepithelial Pagetoid Neoplasms: A Histopathologic Study and Evaluation of Select Features in Paget Disease, Bowen Disease, and Melanoma In Situ.

BACKGROUND: Paget disease, Bowen disease, and malignant melanoma in situ are intraepidermal neoplasms, characterized by the presence of pagetoid scatter of atypical cells in the epidermis. This study reviewed the frequency of select histologic criteria to validate their usefulness in the histologic distinction between these entities. METHODS: One hundred forty-four specimens with the diagnosis of Bowen disease, 144 specimens with Paget disease (mammary and extramammary), and 144 specimens with malignant melanoma in situ were examined microscopically to define frequencies of select histologic criteria present in each disease. RESULTS: Comparison between mammary Paget and extramammary Paget disease showed no significant differences in the features studied. Crushing of basal keratinocytes, presence of atypical cells in the corneum, and presence of large cells with amphophilic cytoplasm were significantly noted in Paget disease. Transition between the atypical clear cells and surrounding keratinocytes was absent in all cases of melanoma in situ and in 87 (60.4%) cases of Paget disease, but it was significantly associated with Bowen disease (98.6%). Dyskeratotic cells were significantly associated with Bowen disease cases. CONCLUSION: Our study demonstrated a practical histologic approach to differentiate between intraepidermal pagetoid neoplasms. Careful histologic study of the proposed criteria may reduce reliance on immunohistochemical stains.

State-of-the-art lasers and light treatments for vascular lesions: from red faces to vascular malformations.

Notable milestones in the treatment of vascular lesions have been achieved over the past century. Many cutaneous vascular lesions can be successfully treated with lightbased devices. In this review, we will discuss the treatment of port-wine birthmarks, lymphatic malformations, infantile hemangiomas, rosacea, venous lakes, pyogenic granulomas, cherry angiomas, and angiofibromas using lasers, total reflection amplification of spontaneous emission of radiation, intense pulsed light, and photodynamic therapy. In addition, for several of these diagnoses, we will review medical therapies that can be combined with light-based devices to provide enhanced results.

Specificity of granular IgM deposition in folliculosebaceous units and sweat gland apparatus in direct immunofluorescence (DIF) of lupus erythematosus.

BACKGROUND: Diagnosis of lupus erythematosus (LE) in direct immunofluorescence testing is based on the finding of positive immunofluorescence at the dermoepidermal junction (DEJ). OBJECTIVES: We sought to evaluate the sensitivity of IgM deposition at the DEJ and adnexal structures in the diagnosis of lupus erythematosus. METHODS: We conducted a retrospective study of 100 previously diagnosed cases of lupus erythematosus and 158 cases of other immune-mediated dermatosis. Deposition of IgG, IgM, IgA, and C3 at the DEJ, follicular units, and sweat glands were recorded. Presence or absence of adnexal structures was documented. The immunoreactant deposition was documented as linear, coarse granular, or stippled. RESULTS: The most frequently deposited immunoreactant in lupus erythematosus cases was IgM along the DEJ and stromal-epithelial junction of hair follicles and sweat glands. IgM deposition along the stromal-epithelial junction of hair follicles and sweat glands was strongly associated with a diagnosis of lupus erythematosus compared with other immune-mediated diseases collectively (P value < .001). The pattern of IgM in lupus and dermatomyositis is granular, in contrast to the linear deposition in the other disorders evaluated. LIMITATIONS: This was a retrospective study of archived material. CONCLUSION: Granular IgM deposition at the stromal-epithelial junction of cutaneous adnexal structures suggests a diagnosis of lupus erythematosus or dermatomyositis.

Nuclear and cytoplasmic features in the diagnosis of banal nevi, Spitz nevi, and melanoma.

BACKGROUND: Many authors have described cytologic features in a variety of melanocytic lesions but, to our knowledge, a statistical analysis of sensitivity, specificity, and overall accuracy of these features alone or in combination has not been performed. OBJECTIVE: We sought to determine the diagnostic value of nuclear and cytoplasmic characteristics in the diagnosis of melanocytic lesions via multivariate statistical analysis. METHODS: This is a retrospective observational study conducted on 300 melanocytic lesions. We evaluated a series of distinctive features; subsequently a multivariate model was used to determine sensitivity and specificity. RESULTS: Major features that favor a diagnosis of melanoma include: pleomorphism with enlarged nuclei, mitotic figures, notching/corrugation of the nuclear envelope, and peppered moth nucleus. Features with intermediate value include: solid hyperchromasia, vesicular nucleus with single round nucleolus, and nuclear/cytoplasmic ratio greater than 4:1. LIMITATIONS: Limitations of this study include its retrospective nature, and the reliance on the original diagnostic classification of each neoplasm. CONCLUSION: Our data suggest that some nuclear alterations have greater value in the diagnosis of benign and malignant melanocytic lesions.

When to suspect tinea; a histopathologic study of 103 cases of PAS-positive tinea.

BACKGROUND: The histopathologic features of tinea vary widely and its diagnosis could be easily missed if the index of suspicion is not high. We aimed in this study to detect histopathologic features that could be a clue for diagnosis METHODS: We retrospectively reviewed 103 cases of tinea, confirmed by Periodic acid-Schiff (PAS) staining. For each case, gender, biopsy site, and pre-biopsy suspicion were recorded. The presence or absence of 17 microscopic features was noted. RESULTS: Concordance between pre-biopsy and histopathologic diagnosis was noted in 57.28% of cases, suggesting that the diagnosis is often not suspected clinically. Among the histopathologic features studied, a compact stratum corneum (either uniform or forming a layer beneath a basket weave stratum corneum), parakeratosis, mild spongiosis and neutrophils in the stratum corneum and within the blood vessels were the most frequent features noted. CONCLUSION: This study suggests histopathologic clues that should prompt the pathologist to order a PAS stain, especially when diagnosis is not suspected clinically.

Pathologic features of anogenital precancerous high-grade squamous intraepithelial lesion (squamous cell carcinoma in situ).

BACKGROUND: Precancerous high-grade squamous intraepithelial lesion (HSIL), the current consensus terminology for anogenital squamous cell carcinoma in situ (SCCIS), often presents with distinctive histopathologic findings that may be a function of anatomic site or associated human papillomavirus infection. METHODS: Fifty-six specimens of anogenital HSIL were compared with an equal number of specimens of SCCIS from non-anogenital sites in regard to the presence of parakeratosis, flag sign in the stratum corneum, compact stratum corneum, hypergranulosis, koilocytes, small blue cells, clonal populations of keratinocytes, pagetoid scatter of atypical keratinocytes, clear cell change, glassy red cytoplasm, pigmentation, nuclear/cytoplasmic(N/C) ratio >2/1, nuclear hyperchromasia, pleomorphic nuclei, mitotic figures, abnormal mitotic figures, dyskeratotic keratinocytes, involvement of skin appendages, acantholysis and amyloid deposition. RESULTS: Hypergranulosis, koilocytes, small blue cells, pigmentation, nuclear hyperchromasia, dyskeratotic keratinocytes and amyloid deposition were more frequently noted in anogenital HSIL. Parakeratosis, clear cell change, pleomorphic nuclei, skin appendages involvement and acantholysis were strongly associated with non-anogenital location. There was no significant difference in the incidence of the remaining features. CONCLUSION: The strongest predicators of an anogenital location included hypergranulosis, koilocytes, small blue cells and nuclear hyperchromasia. Pigmentation and amyloid deposition were also strongly associated with an anogenital location.

Polarized Microscopy in Lesions With Altered Dermal Collagen.

Alterations in dermal collagen are noted in dermatofibroma, dermatofibrosarcoma protuberans, morphea, lichen sclerosus et atrophicus, hypertrophic scars, and keloids. The authors sought to determine whether variations in birefringence of collagen by polarized microscopy could be of help in diagnosing such conditions. Representative hematoxylin and eosin sections of 400 cases, including dermatofibroma, dermatofibrosarcoma protuberans, hypertrophic scars, keloid, morphea, and lichen sclerosus, were examined under polarized microscopy. Distinct patterns of birefringence of collagen for each disease were noted under polarized microscopy. This study highlights the use of polarized microscopy as adjunctive tool in differentiating different diseases with collagen alteration.