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Background The definitive diagnosis of melanocytic neoplasia using solely histopathologic evaluation can be challenging. Novel techniques that objectively confirm diagnoses are needed. This study details the development and validation of a melanoma prediction model from spatially resolved multivariate protein expression profiles generated by Imaging Mass Spectrometry (IMS). Methods Three board-certified dermatopathologists blindly evaluated 333 samples. Samples with triply concordant diagnoses were included in this study, divided into a training set (n = 241) and a test set (n = 92). Both the training and test sets included various representative subclasses of unambiguous nevi and melanomas. A prediction model was developed from the training set using a linear support vector machine (SVM) classification model. Results We validated the prediction model on the independent test set of 92 specimens (75 classified correctly, two misclassified, and 15 indeterminate). IMS detects melanoma with a sensitivity of 97.6% and a specificity of 96.4% when evaluating each unique spot. IMS predicts melanoma at the sample level with a sensitivity of 97.3% and a specificity of 97.5%. Indeterminate results were excluded from sensitivity and specificity calculations. Conclusion This study provides evidence that IMS-based proteomics results are highly concordant to diagnostic results obtained by careful histopathologic evaluation from a panel of expert dermatopathologists. This article is protected by copyright. All rights reserved.

T-cell prolymphocytic leukemia (T-PLL) is a rare, aggressive neoplasm derived from post-thymic T-cells. Patients are typically middle aged with a slight male predominance who present with a high white blood cell count, hepatosplenomegaly, lymphadenopathy, and other symptoms typically associated with leukemia. Although cutaneous involvement has been reported in up to 30% of cases of T-PLL, to our knowledge, none have presented with a presentation resembling livedoid vasculopathy. In the correct clinical context, an underlying hematolymphoid neoplasm should be included in the differential diagnosis of a patient presenting with livedoid vasculopathy.

Context.— Accurate diagnosis of melanocytic lesions is fundamental for appropriate clinical management. Objective.— To evaluate the degree of discordance, if any, between histopathologic diagnoses of melanocytic lesions at referring institutions and at a tertiary referral cancer center and the potential impact of such discordance on clinical management. Design.— We retrospectively identified all patients referred to our comprehensive cancer center for evaluation of a melanocytic lesion from January 2010 to January 2011. For each patient, the histopathologic diagnosis from the referring institution was compared with the histopathologic diagnosis from a dermatopathologist at our center. Discordances were classified as major if they resulted in a change in clinical management and minor if they did not. Results.— A total of 1521 cases were included. The concordance rates were 72.2% (52 of 72) for dysplastic nevus, 75.0% (15 of 20) for all other types of nevi, 91.1% (143 of 157) for melanoma in situ, 96.1% (758 of 789) for invasive melanoma, and 99.6% (478 of 480) for metastatic melanoma. Major discordances were found in 20.2% of cases (307 of 1521), and minor discordances were found in 48.8% of cases (742 of 1521). Compared with the guideline-based treatment recommendation based on the referring-institution diagnosis, the guideline-based treatment recommendation based on the cancer center diagnosis was more extensive in 5.9% (89 of 1521) of patients and less extensive in 5.0% (76 of 1521) of patients. Conclusions.— Our findings underscore the importance of secondary histopathologic review of melanocytic lesions by expert dermatopathologists because significant changes in the diagnosis, tumor classification, and/or staging may be identified, thus, resulting in critical changes in recommendations for clinical management.

Reports of cutaneous reactions to COVID-19 vaccination are increasing as the scope of vaccination expands, and more data are available for study. For example, a recent review of 414 registry patients with dermatologic reactions following mRNA COVID-19 vaccination demonstrated that cutaneous eruptions often occurred in individuals without a dermatologic history and typically arose in the vaccinated arm within days.1 The same study also reported a female predominance of 90% in cutaneous reactions to COVID-19 vaccination. Adding to this body of evidence, we, herein, describe an eruption of lichen striatus occurring several days after COVID-19 vaccination in a middle-aged woman. Of note, there is 1 recently reported case of lichen planus that developed 48 hours following the receipt of the Pfizer vaccine in a patient with a history of successfully treated lichen planus.2 Our case, however, to our knowledge, is the first reported instance of lichen striatus following COVID-19 vaccination, with more profound implications on the pathogenesis of this dermatologic condition.

SMARCA4-deficient thoracic sarcoma (SMARCA4-DTS) is a recently recognized entity with undifferentiated rhabdoid morphology and mutations in the switch/sucrose nonfermenting BRG1-associated factors complex. Patients are typically males in their fifth decade with a history of smoking who present with rapidly progressive intrathoracic disease and follow an aggressive clinical course. Metastatic disease is reported in up to 77% of cases; however, to our knowledge, cutaneous metastasis has not been reported nor has it been reported as the initial manifestation of the disease. Recognizing SMARCA4-DTS from other types of epithelioid tumors that involve the skin is clinically relevant, as targeted therapies for SMARC-deficient tumors are currently being investigated and early clinical trial data show therapeutic benefit.

Cutaneous inflammatory myofibroblastic tumors (IMT) constitute a rare entity, generating a diagnostic pitfall when diagnosing spindle cell proliferation within the dermis. Raising awareness of this tumor among dermatopathologists remains vital in differentiating it from common cutaneous tumors such as fibrous histiocytoma, atypical fibroxanthoma, melanoma, poorly differentiated carcinoma, and other more aggressive tumors. Accurate diagnosis of IMT aids in ensuring appropriate management and follow-up for patients while preventing unnecessary harm and overtreatment. Here we report a case of a 38-year-old female with a painless, slow-growing nodule of the left posterior scalp initially diagnosed as a dermatofibroma. The histopathological examination revealed an ill-defined dermal nodule of spindled cells without connection or infiltration of the epidermis. At high power, the cells were arranged in fascicles with a prominent background of lymphocytic infiltrate. Immunohistochemical analysis showed strong diffuse immunoreactivity for anaplastic lymphoma kinase (ALK), and targeted RNA sequencing identified a CARS-ALK fusion ultimately confirming the accurate diagnosis of a cutaneous IMT.

Although a rare disease, the incidence of congenital syphilis is on the rise in the US. We report a case of early congenital syphilis in a 1-day-old premature boy with positive Rapid plasma reagin titer, respiratory insufficiency, disseminated intravascular coagulation, and encephalopathy, born to a mother with known syphilis infection. Skin examination showed diffuse truncal petechiae, desquamation of the distal extremities, and violaceous, retiform plaques on the buttocks and lower extremities. A biopsy was performed to rule out an infectious etiology or vasculitis. Histopathologic examination revealed irregular epidermal acanthosis with orthokeratosis and parakeratosis. There were foci of neutrophilic infiltrate forming rare pustules within the stratum corneum and focal intraepidermal eosinophils, neutrophils, and rare dyskeratotic keratinocytes. In the dermis, there was some minimal endothelial swelling with a perivascular, interstitial, and periadnexal infiltrate of lymphocytes, eosinophils, and rare plasma cells. A Treponema pallidum immunostain highlighted spirochetes present within the epidermis and within the eccrine ducts. Penicillin G therapy was administered for 10 days. The infant's Rapid plasma reagin titer trended downward until it was negative 6 months after birth. Literature review reveals 8 case reports within the last 20 years describing the histopathology of rashes in congenital syphilis. Herein we summarize the reported histopathology of rashes in congenital syphilis and compare it to the histopathology of rashes in secondary syphilis in adults.

Simple Summary Cutaneous vascular neoplasms of uncertain biological behavior present a diagnostic and therapeutic challenge to physicians. The rarity of these lesions and the recent recognition of such entities suggests an extensive amount of knowledge remains lacking concerning effective treatments, accurate prognosis, and follow-up recommendations for patients with superficial vascular tumors. The objective of this manuscript is to compile a comprehensive summary of the current literature on neoplasms limited to the skin and of vascular origin that are currently categorized as indeterminate biological potential. By compiling numerous studies and summarizing the aggregate findings, this paper aims to offer providers a condensed yet detailed report of the entirety of what is known regarding these lesions. The information will aid physicians in the process of diagnosing, treating, prognosticating, and following up these rare tumors. Abstract Neoplasms of uncertain biological behavior present physicians with a genuine conundrum in practice. Cutaneous vascular neoplasms within this category are exceedingly rare, possessing significant gaps and uncertainty in many facets of clinical practice. Firstly, lesions were selected for review based on their categorization as indeterminate behavior, indicating the potential for local recurrence and rarely metastasize. After identification of the target lesions, a comprehensive review of the literature using national databases produced several landmark studies and case series regarding these neoplasms. Limiting the review to only cutaneous limited tumors narrowed the pool of studies; however, quite a large sum of papers remained. Examination of each paper yielded beneficial results on diagnosing, effective treatments, follow-up findings, and prognosis for each indeterminate lesion discussed. Overall, the literature search combined the molecular, histologic, immunohistochemical, surgical strategies to develop an up-to-date and comprehensive framework to guide physicians when encountering such lesions. The tumors reviewed include: kaposiform hemangioendothelioma, endovascular papillary angioendothelioma, pseudomyogenic hemangioendothelioma, retiform hemangioendothelioma, epithelioid hemangioendothelioma, and composite hemangioendothelioma.

Novel oral anticoagulant (NOAC) medications have revolutionized hematology and cardiology. Recently, NOACs have demonstrated additional promise in dermatology. Specifically, rivaroxaban, a direct factor Xa inhibitor NOAC, has been shown to be successful in the treatment of livedoid vasculopathy. Herein, we describe a patient with systemic lupus erythematosus who presented with painful cutaneous vasculopathy, demonstrated on biopsy with occlusive microvascular fibrin thrombi without evidence of concurrent vasculitis. Interestingly, imaging and laboratory studies did not show evidence of hypercoagulability, arterial disease, or embolic disease. The patient’s vasculopathy and pain progressed despite antiplatelet therapy, often considered first-line in cases of microvascular occlusive disease. However, with rivaroxaban therapy, the patient experienced complete regression of her painful lesions, thereby supporting a further role for NOACs in cutaneous vasculopathy treatment. J Drugs Dermatol. 2020;19(5) doi:10.36849/JDD.2020.4684.

Trichoblastic carcinosarcoma is a rare biphasic adnexal neoplasm. This case report chronicals the eighth occurrence of this tumor published in the English literature and provides a review of the prior publications. Clinically, this tumor presents as an isolated, rapidly growing lesion in elderly patients and is usually cured by complete surgical excision, with no evidence of recurrence or metastasis at follow-up (7/8 cases). Histopathologically, trichoblastic carcinosarcoma is dermal-based, with an epithelial component of basal cells and a mesenchymal component of spindle cells, both of which display malignant features. In addition to a morphologic description of trichoblastic carcinosarcoma, a discussion of the differential diagnoses, including other biphasic neoplasms, is also included. The small number of cases of trichoblastic carcinosarcoma is most likely secondary to under-recognition and underreporting and a larger case volume is needed to more accurately assess the clinical course and treatment strategies.

Low-grade fibromyxoid sarcoma (LGFMS) is a rare soft tissue sarcoma that usually presents as a deep-seated tumor in young adults; however, they can occur on superficial sites, mostly documented in pediatric age groups. LGFMS presenting on acral sites is not highly emphasized in the general pathology or dermatopathology literature. The case presented is that of a 30-year-old man with a foot mass that was removed 15 years earlier and subsequently recurred as two masses, the first occurring between the third and fourth toes/metatarsal region and the second over the lateral tarsal region. An excisional biopsy showed a relatively circumscribed, bland spindle cell proliferation with hypocellular and hypercellular zones. The cells showed minimal pleomorphism and lacked mitotic activity. Immunohistochemical analysis showed immunoreactivity for MUC4 and break-apart fluorescence in situ hybridization was positive for FUS rearrangement, confirming the diagnosis of LGFMS. There are multiple spindle cell tumors that occur on acral sites which usually generates a list of differential diagnoses; however, LGFMS is not usually discussed in that anatomic location. Awareness of the occurrence of LGFMS on acral sites is important to avoid misdiagnosis of this deceptively benign-appearing tumor.

Cutaneous angiosarcoma presents clinically in numerous ways, and can be mistaken for a different clinical entity, particularly when arising at unusual anatomic locations such as the eyelid.A 57-year-old woman presented with a 1-year history of eyelid swelling. Concurrent imaging was also suggestive of an edematous process. Multiple superficial biopsies showed nonspecific dermal inflammation and interstitial edema. A diagnosis of Morbihan disease (chronic and idiopathic lymphedema of the eyelid) was rendered, and the patient was treated with compression and local therapy without clinical improvement. Three years after initial presentation, a diagnostic blepharoplasty was performed revealing a deep dermal vascular proliferation composed of anastomosing vascular channels with an atypical endothelial lining. A diagnosis of cutaneous angiosarcoma was ultimately made.This case illustrates a unique presentation of cutaneous angiosarcoma and the implications of different biopsy techniques in acquiring the correct diagnosis.

Mycosis fungoides (MF) is the most common variant of cutaneous T-cell lymphomas. Large-cell transformation of MF has been associated with disease progression and overall poor outcome. The expression of CD30, which defines anaplastic large cell lymphoma (ALCL) and lymphomatoid papulosis, might also occur in a subset of patients with MF, with or without large-cell transformation. Brentuximab vedotin is an anti-CD30 monoclonal antibody which has been proven to be a safe and effective therapeutic agent in the treatment of CD30-positive lymphomas, such as Hodgkin lymphoma and ALCL. Recently, brentuximab vedotin has been shown to have a significant clinical activity in treatment-refractory or advanced MF or Sezary syndrome with a wide-range of CD30 expression levels. We report a patient with MF tumor stage with large-cell transformation and low CD30 expression with good response to brentuximab vedotin and unusual extensive xanthomatous changes in the follow-up biopsy.

We describe a 44-year-old female with triple-negative breast cancer who developed skin erythaema, sclerosis and contracture of her entire right breast 15 months after completion of post-lumpectomy chemotherapy and radiotherapy, consistent with post-irradiation morphoea (PIM). PIM is a rare complication of breast irradiation that impairs a patient's quality of life. PIM is located usually at the radiation port or in the surrounding tissue. Clinically, PIM is misdiagnosed commonly as lymphoedema and cellulitis in the early inflammatory phase, and recurrent breast cancer, chronic radiodermatitis (CRD), radiation-induced fibrosis (RIF), post-irradiation pseudosclerodermatous panniculitis (PIPP), atypical vascular lesions (AVL) or angiosarcoma (AS) in the late burnout phase. Arriving at the correct diagnosis typically requires a multidisciplinary approach, including a skin biopsy for confirmation. To date, satisfactory treatment of this condition has been challenging. and the clinical outcome after therapy is often unsatisfactory.

Pediatric dermatopathology includes a range of diseases, particularly inflammatory and genodermatosis, that pathologists may not be entirely familiar with. Furthermore, children are not biopsied frequently, and this limits the understanding of the histopathologic features in pediatric skin disorders. Some diseases may only be encountered early in life, and the differential diagnosis of certain conditions in children is different from that considered in adults. This chapter covers pediatric dermatopathology in the hospital setting.

Background Mucoepidermoid pancreatic cancer is a rare entity with only 8 cases reported in the literature. On review of the literature, the authors found that cutaneous metastases in pancreatic cancer are rare and have not been associated with the mucoepidermoid subtype. The authors present the first reported case of cutaneous metastasis in a patient with mucoepidermoid carcinoma of the pancreas. Case presentation A 50-year old white male with a metastatic invasive poorly differentiated mucoepidermoid carcinoma of the pancreas was found to have a slow growing lesion in the skin over his left upper quadrant while undergoing active therapy. The lesion was biopsied and the pathology was consistent with pancreatic origin sharing similar morphologic features when compared with the primary pancreactectomy specimen. Conclusions Mucoepidermoid pancreatic cancer is an exceedingly rare subtype of pancreatic cancer, with very little information regarding its diagnosis, treatment, and patterns of metastases. Here, the authors present the first reported case of cutaneous metastases of mucoepidermoid pancreatic cancer.

Anaplastic large cell lymphoma (ALCL) is an aggressive T-cell lymphoma characterized by strong and uniform expression of CD30. Brentuximab vedotin (BV), an anti-CD30 antibody-drug conjugate has been approved by the U.S. FDA for relapsed/refractory systemic ALCL and achieves improved outcomes. We report a 44-year-old African-American man who presented with lymphadenopathy, lip and chest nodules diagnosed as CD30+, ALK-negative ALCL. The patient was treated with BV upon recurrence. While on treatment, the patient developed new-onset nodules on the chest and back. Skin biopsy showed a diffuse dermal infiltrate of medium-to-large atypical lymphocytes with frequent mitosis and scattered eosinophils. Immunohistochemically, the atypical cells displayed the same immunophenotype as previous specimens (CD3+, CD4-/CD8-, CD56-, ALK- and TCR γ-), except for lack of CD30 expression which was attributed to BV treatment effect. The diagnosis was thought to be consistent with ALK-negative ALCL and the patient was continued on BV along with total skin electron beam radiation and the lesions cleared. The patient relapsed 2 months later with extensive disease and expired. In summary, this is the first report in the literature of loss of CD30 expression in ALCL after BV therapy. Awareness of this may prevent a mistaken diagnosis of a CD30-negative secondary T-cell lymphoma.

A minority of eyelid hidrocystomas are pigmented containing brown-black contents. Chromhidrosis describes the excretion of colored secretions composed of lipofuscin pigments in apocrine gland-rich anatomic locations. The objective of this study is to evaluate the clinicopathologic features of pigmented eyelid cysts. A case-control study was conducted, examining consecutive pigmented and nonpigmented eyelid hidrocystoma excision specimens. Over a 4-year period, 9 pigmented eyelid hidrocystomas were identified, representing 13% (9/70) of all hidrocystoma excisions. Compared to controls (n = 14), no difference existed for age [mean age 59 (44-78 years) vs. 60 (42-82 years)] or size [mean diameter 2.3 (1-4 mm) vs. 2.7 (1-5 mm)] (pigmented vs. nonpigmented, respectively), but a trend for female, left side, and lower lid predominance for pigmented hidrocystomas existed: 8:1 versus 7:7 F:M; 7:2 versus 7:7 left:right; 8:1 versus 9:5 lower:upper eyelid (pigmented vs. nonpigmented, respectively). Clinically, the pigmented cysts' color varied from dark blue, brown, and to black, and on gross examination, they expressed dark brown to black granular liquid contents. Applying histologic criteria of Jakobiec and Zakka, 8 of 9 and 14 of 14 pigmented and nonpigmented hidrocystomas were of apocrine type. Seven of 9 (78%) pigmented cysts and 6 of 14 (43%) nonpigmented hidrocystomas contained granular eosinophilic cyst contents and/or intracellular cytoplasmic granular pigmented deposits by light microscopy. (The pigmented cyst contents did not survive processing in 2 cases.) By histochemistry (periodic acid Schiff with diastase, Sudan Black, and Fite acid-fast positive staining) and ultraviolet fluorescence, these sediments were determined to be lipofuscin pigments. No hidrocystomas had melanin deposits, and one case had hemosiderin deposits in a scarred cyst wall in addition to cyst lipofuscin pigments. In studies of chromhidrosis, both normal and chromhidrotic apocrine glands contain lipofuscin pigments; the sole difference lies in the amount of lipofuscin granules. Similarly, for eyelid apocrine hidrocystomas, lipofuscin pigments exist in both groups. Presumptively, the amount of lipofuscin and degree of its oxidation distinguish pigmented from nonpigmented apocrine hidrocystomas.

Summary The diagnosis of melanocytic lesions remains a formidable challenge in dermatopathology. For diagnostically challenging lesions, ancillary tests are available to inform the diagnosis, including immunohistochemistry and molecular testing (particularly fluorescence in situ hybridization [FISH]). However, the test result that most robustly informs the diagnosis remains controversial. Thirty-seven diagnostically challenging melanocytic lesions from our consultation service were reviewed. Histopathologic, immunohistochemical, and second-generation FISH results (NeoGenomics; probes 6p25, 8q24, 11q13, 9p21, and centromere 9) were correlated with the final consensus diagnosis and clinical follow-up using logistic regression and Fisher exact test. Based on histopathologic and immunohistochemical features, cases were designated as "favor benign" (n=19) or "favor malignant" (n=18) by a consensus group of up to 7 dermatopathologists. The sensitivity of FISH for the diagnosis of melanoma was 39%, and the specificity was 84%. Univariate logistic regression models for a final diagnosis of melanoma showed that only increased Ki-67–positive dermal tumor cells (≥5%; P =.01) significantly correlated with the diagnosis of melanoma. FISH result did not correlate with the final diagnosis (melanoma or nevus; P =.26). Follow-up (range, 8-29months) was available for 35 cases (19 diagnosed as nevus and 16 as melanoma), and metastases (restricted to sentinel lymph nodes) were detected from 5 melanomas (3 FISH negative and 2 FISH positive). Only increased dermal mitotic figures (>1/mm 2 ) correlated with metastases to sentinel lymph nodes ( P =.04). Thus, in the classification of diagnostically challenging melanocytic lesions, indices of proliferation emerge as the most informative diagnostic adjuncts—correlating with diagnosis and clinical behavior, respectively.

To describe severe lymphedema of the eyelids, known as Morbihan disease, a previously characterized but infrequently reported and poorly understood entity related to rosacea that features solid mid-facial and eyelid lymphedema. Retrospective chart review, histopathologic and immunohistochemical analysis, and pertinent literature consideration. Five cases of Morbihan disease were identified. Histopathologic examination revealed pleomorphic perivascular and perilymphatic inflammation with profound lymphangiectasis and lymph stasis, thus suggesting elements of both rosacea and localized, chronic lymphedema. Multiple therapeutic interventions were performed including systemic anti-inflammatory therapy, surgical debulking, and corticosteroid injection. Extreme eyelid edema associated with characteristic skin changes and histopathologic findings represents an entity known as Morbihan disease which is rare and difficult to treat. While multiple modalities have been employed with variable results, future therapeutic considerations may include the use of targeted biologic agents.

Mosaicism is a biologic phenomenon that describes an individual who has two or more populations of cells with distinct genotypes and concomitant patterned phenotypes (eg, lines of Blaschko). It is distinguished from chimerism by its derivation from a single fertilized egg rather than multiple cell lineages derived from distinct fertilized eggs. With respect to dermatologic disorders, it is the strongest genetic example of how a cutaneous site, being populated by cells with distinct antigenic or immunologic properties, differs in its susceptibility or resistance to skin disorders, being preferentially affected in the former (ie, locus minoris resistentiae). We review patterns and mechanisms of skin mosaicism and discuss examples of segmental/mosaic dermatologic disorders that have been superimposed on a background of a nonsegmental eruption of the same disease or dermatologic disorders that have arisen secondarily on segmental cutaneous disorders.