Severe Esophageal Lichen Planus Treated With Tofacitinib.

Lichen planus is a chronic inflammatory immune disorder that most commonly affects the skin and mucous membranes. Esophageal lichen planus (ELP) is a frequently misdiagnosed and poorly understood form of lichen planus that can be asymptomatic or present with dysphagia and odynophagia caused by the formation of erosions and strictures in the esophagus. These strictures often reduce a patient's quality of life and may lead to emaciation in more severe cases. We present the case of an 89-year-old woman with a history of cutaneous lichen planus (CLP) and mucosal lichen planus that were successfully managed with topical corticosteroids and oral cyclosporine rinses who presented with an esophageal stricture and erosions that were treated unsuccessfully with surgery. Our patient's condition continued to worsen until she presented in an emaciated state and was treated with tofacitinib, which resulted in complete resolution of oral lichen planus (OLP), ELP, and genital lichen planus.

Human Polyomavirus 9-An Emerging Cutaneous and Pulmonary Pathogen in Solid Organ Transplant Recipients.

IMPORTANCE: We describe the first report to our knowledge of cutaneous and systemic pathogenicity of human polyomavirus 9 in solid organ transplant recipients. OBJECTIVE: Three solid organ transplant recipients developed a widespread, progressive, violaceous, and hyperkeratotic skin eruption. All died from pulmonary and multiorgan failure around 1 year from onset of the rash. Routine clinical diagnostic testing could not identify any causative agent; therefore, samples and autopsies were investigated for novel pathogens using high-throughput sequencing. DESIGN, SETTING, AND PARTICIPANTS: This case series, including 3 solid organ transplant recipients who developed characteristic pink, violaceous, or brown hyperkeratotic papules and plaques throughout the body, was conducted at the Columbia University Medical Center. Lesional skin biopsies were collected from all 3 patients and subjected to high-throughput illumina sequencing for identification of microbial pathogens. Human polyomavirus 9 was identified in lesional skin biopsies. We subsequently collected ocular swabs, oral swabs, urine samples, and blood samples from patients, and organ tissues at autopsy in 1 patient. We investigated these samples for the presence of human polyomavirus 9 using in situ hybridization and quantitative polymerase chain reaction (PCR) assays. MAIN OUTCOMES AND MEASURES: A description of the clinical and pathologic findings of 3 patients. RESULTS: This case series study found that human polyomavirus 9 was detected in the skin biopsies of all 3 patients by a capture-based high-throughput sequencing method platform (VirCapSeq-VERT). Human polyomavirus 9 was also detected in blood, oral, ocular swabs, and urine by real-time polymerase chain reaction (PCR) assay. In situ hybridization and quantitative PCR assays were performed on the skin biopsies from 3 patients and lung autopsy of 1 patient, which showed the presence of human polyomavirus 9 messenger RNA transcripts, indicating active viral replication and pathogenesis in the skin and lungs. CONCLUSIONS AND RELEVANCE: Human polyomavirus 9 was associated with the widespread cutaneous eruption. All 3 patients had progression of cutaneous disease, accompanied by clinical deterioration, pulmonary failure, and death. One patient underwent autopsy and human polyomavirus 9 was identified in the lungs and paratracheal soft tissue. These findings suggest that human polyomavirus 9 may be associated with cutaneous and possibly pulmonary infection and death in solid organ transplant recipients.

Unique histopathologic features of the eyelid dermatofibroma.

Purpose: Dermatofibromas are common cutaneous lesions, but rarely occur in the eyelid skin. The reason for the low incidence in the palpebral skin has not been elucidated. In this study, we analyze the histopathologic features of an illustrative case of dermatofibroma and review previously published cases to determine whether eyelid dermatofibroma develops differently from the prototypical dermatofibroma. Methods: Histopathologic analysis of a new illustrative case of eyelid dermatofibroma and retrospective review of published cases. Results: The distinguishing features of the illustrative lesion included a rounder gross appearance, nonacanthotic epithelium, basophilic staining, cellular character, and a paucity of "collagen trapping." These features deviated from the typical features associated with classic dermatofibroma. Review of the 11 previously published cases of eyelid dermatofibroma revealed that they were more similar in appearance to the illustrative lesion than to classic dermatofibroma. Discussion: The rarity and histological deviations of the eyelid dermatofibroma suggest that the dermal substrate from which the lesion develops differs from that of the classic dermatofibroma. This difference may be explained microanatomically based on the fact that the dermis of the eyelid is predominantly papillary, whereas the dermis of extrapalpebral skin where dermatofibromas are more common is predominantly reticular. Conclusions: Although related, eyelid dermatofibromas appear to be histologically distinct from classic dermatofibromas, owing to the unique dermal composition of the site of origin.

Cutaneous Presentation of Mesothelioma With a Sarcomatoid Transformation.

Malignant pleural mesothelioma is a rare neoplasm of mesodermal origin. Cutaneous involvement of malignant pleural mesothelioma is a very rare entity, with only 11 cases reported in the literature. Here, we describe the case of a 75-year-old man with stage IV epithelioid pleural mesothelioma, presenting with a cutaneous eruption 5 months after initial diagnosis, which revealed sarcomatoid features on skin biopsy. Histological analysis of malignancy progression through immunohistochemical staining of the pleural, lymph node, and skin tissue revealed gradual loss of calretinin and gain of desmin, supporting a transformation from epithelioid to sarcomatoid tissue. To our knowledge, this is the first reported case of an epithelioid to sarcomatoid transformation of malignant pleural mesothelioma manifesting in a cutaneous presentation.

Genomic Characterization of Dysplastic Nevi Unveils Implications for Diagnosis of Melanoma.

A well-defined risk factor and precursor for cutaneous melanoma is the dysplastic nevus. These benign tumors represent clonal hyperproliferation of melanocytes that are in a senescent-like state, but with occasional malignant transformation events. To portray the mutational repertoire of dysplastic nevi in patients with the dysplastic nevus syndrome and to determine the discriminatory profiles of melanocytic nevi (including dysplastic nevi) from melanoma, we sequenced exomes of melanocytic nevi including dysplastic nevi (n = 19), followed by a targeted gene panel (785 genes) characterization of melanocytic nevi (n = 46) and primary melanomas (n = 42). Exome sequencing revealed that dysplastic nevi harbored a substantially lower mutational load than melanomas (21 protein-changing mutations versus >100). Known "driver" mutations in genes for melanoma, including CDKN2A, TP53, NF1, RAC1, and PTEN, were not found among any melanocytic nevi sequenced. Additionally, melanocytic nevi including dysplastic nevi showed a significantly lower frequency and a different UV-associated mutational signature. These results show that although melanocytic nevi and dysplastic nevi harbor stable genomes with relatively few alterations, progression into melanomas requires additional mutational processes affecting key tumor suppressors. This study identifies molecular parameters that could be useful for diagnostic platforms.

Clinical efficacy of short contact topical 5-Fluorouracil in the treatment of keratoacanthomas: a retrospective analysis.

OBJECTIVE: To determine the efficacy of treating patients with a recent onset, biopsy-proven keratoacanthoma with short-contact topical 5% 5-fluorouracil cream twice daily until resolution. DESIGN: Chart review of 10 patients who applied 5% 5-fluorouracil for the treatment of biopsy-proven keratoacanthoma. SETTING: Outpatient clinic of a board-certified dermatologist. PARTICIPANTS: The study population was 90-percent women (9/10), 10-percent men (1/10) and ranged in ages from 52 to 92 years old with a mean age of 74.4. MEASUREMENTS: Patients were followed for weekly visits for the duration of their treatment and at varying, less-frequent intervals after resolution of the lesion clinically. Photographs were taken at each visit. RESULTS: The authors performed a retrospective analysis of 10 patients with biopsy-confirmed keratoacanthomas treated with topical 5-fluorouracil. One patient elected to have Mohs surgery after one week of topical 5-fluorouracil due to personal concern and cosmetic appearance and did not complain of any side effects due to the drug. Of the nine patients that remained on topical 5-fluorouracil, all patients had complete resolution of the lesion within six weeks. The range in the number of weeks to resolution was four to six weeks. Two patients required a one- to two-week drug holiday secondary to erythema, which resolved without any further complication or patient discomfort. All nine patients who continued therapy reported satisfaction with the results and showed excellent compliance with treatment. CONCLUSION: Short-contact topical 5% 5-fluorouracil appears to provide excellent cosmetic results and is well-tolerated by patients. This should be an initial consideration for the treatment of keratoacanthomas and does not preclude future surgical intervention if deemed necessary.

A tumor suppressor function for the lipid phosphatase INPP4B in melanocytic neoplasms.

The phosphoinositide-3 kinase (PI3K) pathway is deregulated in a significant proportion of melanomas, and PI3K pathway activation in combination with constitutively active mitogen-activated protein kinase signaling shows synergistic effects in the process of melanoma tumorigenesis. Recently, a tumor suppressor function for the lipid phosphatase inositol polyphosphate 4-phosphatase type II (INPP4B) has been described in breast and prostate cancers, with impact on PI3K signaling output. Given the importance of PI3K pathway activity for melanoma formation and growth, we aimed to assess the role of INPP4B in melanocytic tumors. Our studies in native tumors suggest that decreased INPP4B expression is an event correlating with tumor progression in melanocytic neoplasms. We further demonstrate that INPP4B regulates PI3K/Akt signaling and exerts a tumor suppressor effect, impacting the proliferative, invasive, and tumorigenic capacity of melanoma cells. INPP4B expression in melanocytic neoplasms may therefore have potential as a biomarker for disease progression and as a modulator for the prediction of treatment outcome.

A diagnostic algorithm to distinguish desmoplastic from spindle cell melanoma.

Spindle cell melanoma and desmoplastic melanoma differ clinically in prognosis and therapeutic implications; however, because of partially overlapping histopathological features, diagnostic distinction of spindle cell from desmoplastic melanoma is not always straightforward. A direct comparison of diagnostic and therapeutic biomarkers has not been performed. Meta-review of the literature discloses key clinicopathological differences between spindle cell and desmoplastic melanoma, including immunophenotypes. Using 50 biomarkers available in routine diagnostics, we examined 38 archival cases (n=16 spindle, 18 desmoplastic, 4 mixed spindle/desmoplastic melanoma). S100 remains as the most reliable routine marker to reach the diagnosis of melanoma in spindle cell and desmoplastic melanoma. We identified nine distinctly labeling markers with spindle cell melanoma showing positivity for laminin, p75, HMB45, c-kit, and MelanA, and desmoplastic melanoma preferentially labeling with collagen IV, trichrome, CD68, and MDM2. On the basis of comparisons of test performance measures, MelanA and trichrome were used to devise a 94% sensitive diagnostic algorithm for the distinction of desmoplastic from spindle cell melanoma. Gene amplification and expression status was assessed for a set of potentially drugable targets (HER2, EGFR, MET, MDM2, TP53, ALK, MYC, FLI-1, and KIT). Fluorescent in situ hybridizations did not reveal a significant number of gene aberrations/rearrangements; however, protein overexpression for at least one of these markers was identified in 35 of 38 cases (92%). In addition, we found BRAF mutations in 31% of spindle cell and 5% of desmoplastic melanoma, with an overall mutation frequency of 16% (n=6/38). We present the first comprehensive screening study of diagnostic and therapeutic biomarkers in spindle cell and desmoplastic melanoma. The devised algorithm allows diagnostic distinction of desmoplastic from spindle cell melanoma when routine histology is not decisive.

9p21 gene locus in Spitz nevi of older individuals: absence of cytogenetic and immunohistochemical findings associated with malignancy.

The diagnosis of Spitz nevus in an elderly individual is often met with skepticism because the lesion can be difficult to distinguish from melanoma and because the probability of a malignant melanoma is higher in older patients. Recently, increased sensitivity for detection of malignant spitzoid neoplasms using 9p21 fluorescence in situ hybridization (FISH) has been described. In this study, we address the question of whether histopathologically typical Spitz nevi occurring in patients 50 years and older show any abnormalities regarding the 9p21 CDKN2A tumor suppressor gene locus. p16 immunohistochemistry (IHC), as well as dual-color FISH for assessment of diploid or hypodiploid status at 9p21, was performed in 25 classic Spitz nevi from patients 50 years and older and was compared with findings in a younger control population. All cases of typical Spitz nevi occurring in older patients retained p16 expression by immunohistochemistry and showed normal, diploid 9p21 FISH signals. Heterozygous loss of 9p21 by FISH was noted in a control case of a 9-year-old girl and is of unknown significance. These findings indicate that p16 expression by immunohistochemistry in classic Spitz nevi correlates well with absence of malignancy-associated cytogenetic abnormalities at 9p21 by FISH independent of the patient's age. Assessment of p16 expression by standard immunohistochemistry may therefore be reassuring in routine clinical practice when the patient is of advanced age, and can be helpful as a screening tool to select IHC-negative cases for extended FISH analysis targeting the 9p21 gene locus.

Chromosomal aberrations by 4-color fluorescence in situ hybridization not detected in Spitz nevi of older individuals.

OBJECTIVE: To investigate whether Spitz nevi with typical histopathological features in older patients demonstrate chromosomal aberrations by 4-color fluorescence in situ hybridization (FISH). DESIGN: Retrospective medical record review, with prospective masked histopathological and cytogenetic analyses. SETTING: University-affiliated dermatology and dermatopathology setting. PATIENTS: Twenty-five patients 50 years or older with melanocytic nevi showing histopathological features typical of Spitz nevi. MAIN OUTCOME MEASURES: Three dermatopathologists masked to the patients' ages reviewed histopathological sections of melanocytic lesions for features typical of Spitz nevi. FISH was performed on samples with typical histopathological features by a 4-color FISH probe set used for the evaluation of malignant melanocytic neoplasms. RESULTS: None of the study cases showing histopathological features typical of Spitz nevi had detectable chromosomal abnormalities by FISH. CONCLUSIONS: Spitz nevi in older patients demonstrate molecular features similar to those of Spitz nevi in younger age groups. The findings of normal karyotypes in combination with typical histopathological features are reassuring of Spitz nevus diagnoses in older patients and suggest no correlation of increased malignant potential with advanced age per se.