Metastatic Pancreatic Adenocarcinoma to Umbilical Skin.

Sister Mary Joseph nodule (SMJN) is a rare metastasis to umbilical skin originating from internal tumors including the stomach, ovary and large intestine and less commonly from pancreatic cancers. We report an uncommon case of metastatic pancreatic adenocarcinoma to umbilical skin. An 85-year-old female presented with a 1.8 cm protrusion of the right lateral umbilicus. The CT scan showed a 3.5 cm pancreatic lesion, peritoneal carcinomatosis and abdominal lymphadenopathy. Histology examination revealed atypical infiltrative glandular structures. Immunohistochemistry showed positive CK7, negative CDX2 and P53 with mutated patterns. These were consistent with metastatic adenocarcinoma most consistent with pancreatobiliary or upper GI origin. CK7 expresses in the ductal cells in pancreatic ductal adenocarcinoma. While CDX2 is positive in intestinal-type adenocarcinoma, it is negative in pancreatic ductal adenocarcinoma. The diagnosis of adenocarcinoma is rendered based on the presence of a pancreatic lesion in CT scan, positive CK7 and negative CDX2 in umbilical nodule tumor cells in the current patient.

Dual-Positive CD4/CD8 Primary Cutaneous Peripheral T-Cell Lymphoma Previously Classified as Mycosis Fungoides a Tumor D'Emblée.

Cutaneous peripheral T-cell lymphoma, not otherwise specified represents a "waste basket" of all cases that cannot be put into another of the categories of mature cutaneous T-cell lymphoma. Previously, the sudden multifocal development of cutaneous CD4 tumors without preceding a patch or plaque stage was classified as d'emblée form of mycosis fungoides (MF). Currently, the term "MF" reserved only for the classic Alibert-Bazin type characterized by the evolution of patches, plaques, and tumors or for variants showing a similar clinical course. The authors describe a 75-year-old white woman who presented with a solitary skin tumor in the right supraclavicular region, with no lymph node or systemic involvement. Local external beam radiation treatment resulted in a complete response. The patient relapsed after 5 months with new tumors in the left neck and left upper chest. Biopsy of the lesions showed a dermal infiltrate of atypical small- to medium-sized T-lymphocytes, and immunohistochemical staining showed coexpression of CD4/CD8 in a subset of these cells, which was confirmed with flow cytometry of the tumor. Although the patient had no preceding patch or plaque stage, the authors herein report this extremely rare case of CD4/CD8 dual-positive peripheral T-cell lymphoma, not otherwise specified presented as MF d'emblée and discuss the seldom similar cases published previously.

Cutaneous manifestation of gastrointestinal disease.

The gastrointestinal (GI) and cutaneous systems are closely linked in origin. Skin manifestations are frequently seen as a part of different GI syndromes. Gastroenterologists play an important role in recognizing the symptoms, patient workup and arriving at appropriate diagnoses, often in consultation with dermatologists. This review discusses the diseases with both cutaneous and intestinal involvement. Hereditary polyposis GI cancers, hereditary nonpolyposis colorectal cancers (CRCs), hamartomatous disorders, and inflammatory bowel disease (IBD) are reviewed with emphasis on the genetic basis, diagnostic, histologic findings, screening modalities, and therapeutic options.

Systemic Hyalinosis With Heterozygous CMG2 Mutations: A Case Report and Review of Literature.

Juvenile hyaline fibromatosis (JHF) is a rare autosomal recessive disorder characterized by hyalinizing fibrosis of the skin and internal organs. Clinical features include multiple papular skin lesions, gingival hyperplasia, joint contractures, and osteolytic bone lesions. The systemic variant of JHF, known as infantile systemic hyalinosis (ISH), has an early onset and poor prognosis. Histological examination of cutaneous lesions shows bland-appearing fibroblasts within amorphous eosinophilic hyaline depositions. JHF and infantile systemic hyalinosis form a clinical spectrum with higher mortality that is typically observed in systemic cases. Here, the authors present a case of systemic hyalinosis with a heterozygous mutation in CMG2 that resulted in improved survival.

Pigment-Synthesizing Melanocytic Neoplasm With Protein Kinase C Alpha (PRKCA) Fusion.

IMPORTANCE: Melanocytic neoplasms with prominent pigment synthesis mimicking equine melanoma represent a rare variant of biologically indeterminate or low-grade malignant melanocytic tumors in which the molecular profile and exact histologic classification are not established. Tumors with these characteristics rarely occur as congenital lesions. We performed genomic analysis of a congenital pigment synthesizing melanocytic neoplasm with indeterminate biological potential. OBSERVATIONS: The patient was a 5-month-old girl presenting with a 6-cm protuberant scalp mass, which had doubled in size since birth. Histologic examination showed heavily pigmented intradermal proliferation of large, epithelioid melanocytes with mild cytologic atypia, low mitotic activity, focal necrosis, and ulceration. RNA sequencing identified a novel ATPase, Ca2+ transporting, plasma membrane 4(ATP2B4)-protein kinase C-alpha (PRKCA) fusion transcript. The fusion resulted in an in-frame linkage of the PRKCA catalytic domain with the N-terminal of ATP2B4 and high expression of the PRKCA kinase domain. Break-apart fluorescence in situ hybridization showed PRKCA rearrangement, and reverse transcriptase-polymerase chain reaction confirmed the presence of the fusion transcript. The patient was alive and well, with no evidence of recurrence, at the 1-year follow-up. CONCLUSIONS AND RELEVANCE: To our knowledge, this is the first report of PRKCA fusions in melanocytic neoplasms. Future studies need to determine the frequency of PRKCA fusions in pigment-synthesizing melanocytic neoplasms.

Evaluating clinical trial design: systematic review of randomized vehicle-controlled trials for determining efficacy of benzoyl peroxide topical therapy for acne.

Determined efficacies of benzoyl peroxide may be affected by study design, implementation, and vehicle effects. We sought to elucidate areas that may allow improvement in determining accurate treatment efficacies by determining rates of active treatment and vehicle responders in randomized controlled trials assessing the efficacy of topical benzoyl peroxide to treat acne. We conducted a systematic review of randomized vehicle-controlled trials evaluating the efficacy of topical benzoyl peroxide for the treatment of acne. We compared response rates of vehicle treatment arms versus those in benzoyl peroxide arms. Twelve trials met inclusion criteria with 2818 patients receiving benzoyl peroxide monotherapy treatment and 2004 receiving vehicle treatment. The average percent reduction in total number of acne lesions was 44.3 (SD = 9.2) and 27.8 (SD = 21.0) for the active and vehicle treatment groups, respectively. The average reduction in non-inflammatory lesions was 41.5 % (SD = 9.4) in the active treatment group and 27.0 % (SD = 20.9) in the vehicle group. The average percent decrease in inflammatory lesions was 52.1 (SD = 10.4) in the benzoyl peroxide group and 34.7 (SD = 22.7) in the vehicle group. The average percentage of participants achieving success per designated study outcomes was 28.6 (SD = 17.3) and 15.2 (SD = 9.5) in the active treatment and vehicle groups, respectively. Patient responses in randomized controlled trials evaluating topical acne therapies may be affected by clinical trial design, implementation, the biologic effects of vehicles, and natural disease progression. "No treatment" groups may facilitate determination of accurate treatment efficacies.

Postinflammatory hyperpigmentation secondary to external insult: an overview of the quantitative analysis of pigmentation.

CONTEXT: Despite new technologies, few studies have quantified changes in melanocyte numbers associated with postinflammatory hyperpigmentation (PIH) secondary to exogenous causes. OBJECTIVE: This article aims to review what is known about the pathogenesis of PIH secondary to external insults and its relationship to the resultant degree of quantitative changes in melanocytes. METHODS: We performed a review of articles exploring PIH resulting from external cutaneous insults retrieved through database searching. We reviewed relevant articles for the pathogenesis, histopathology, and quantitative changes in melanocytes related to specific etiologies of PIH. Methodologies to quantify pigmentation changes in dermatologic conditions with clinical hyperpigmentation were also explored. RESULTS: Significant increases in melanocyte counts of irritant affected skin is seen compared with melanocyte counts of unaffected skin. An increase in melanocyte counts was also found for spontaneous inflammatory dermatoses, even in the absence of clinical hyperpigmentation. Furthermore, changes in melanocyte density and appearance are also seen secondary to inflammation. In addition, increases in epidermal melanocytes are seen with cutaneous exposure to certain agents, and melanocyte increases vary by exposure agent. CONCLUSIONS: The degree of hyperpigmentation related to the intensity and duration of exposure to the causative factors of PIH is essential to better understand the pathophysiology of the disease process. The application of new methodologies to determine quantitative changes in melanocytes elicited by specific causative inflammatory agents has implications to prevent PIH, add to knowledge about disease duration, to develop better treatments for PIH, and to aid our understanding of the biology of the melanocyte.

Randomized, vehicle-controlled trials of topical 5-fluorouracil therapy for actinic keratosis treatment: an overview.

Actinic keratoses are common in older individuals and topical immunotherapy is an important treatment when multiple lesions are present. To assess the efficacy of 5-fluorouracil in treating actinic keratoses, a systematic review of randomized, vehicle-controlled trials was performed. Percentages of 5-fluorouracil and vehicle responders were determined by absolute clearance and mean percent reduction in lesion count. Four trials with 399 and 269 participants in active treatment and vehicle groups, respectively, were evaluated. After 4 weeks of treatment, total clearance and mean lesion count reduction were 52.6 and 90.2% in the treatment group versus 0.85 and 28.3% in the vehicle group, respectively. Topical 5-fluorouracil is efficacious in treating actinic keratoses; however, vehicle responses warrant further investigation of study design and disease severity scales.