Dermatopathology

Encephalocraniocutaneous lipomatosis (ECCL) is a rare congenital neurocutaneous disorder characterized by ocular, skin, and central nervous system manifestations. Despite its recognizable clinical features, such as nevus psiloliparus, histopathologic characterization of ECCL remains limited in the dermatopathology literature, and diagnosis is often clinical. This scarcity of published histopathological descriptions makes diagnostic confirmation challenging and underscores the value of synthesizing the available evidence. This comprehensive review synthesizes reported histopathological findings across cutaneous manifestations highlighting key tissue-level features that may aid diagnostic confirmation. Additionally, we review the emerging role of molecular diagnostics, particularly the identification of mosaic activating mutations in FGFR-1 and KRAS, which have been implicated in ECCL pathogenesis. By integrating clinicopathologic correlations with molecular insights, this review aims to enhance our dermatopathological understanding of ECCL, bolstering diagnostic reasoning and clinical decision making for this rare neurocutaneous condition.

Background/Objectives: Oral focal mucinosis (OFM) and solitary cutaneous focal mucinosis (SCFM) are rare, benign lesions characterized by localized mucin deposition in the stromal connective tissue. While both share similar histological features, they occur in distinct anatomical sites and clinical contexts and have not been directly compared in the literature. Method: This study presents a case series of 39 OFM cases diagnosed over 25 years, supplemented by a literature review of previously reported OFM cases, and compares the combined data with published cases of SCFM. The literature-based analysis included 116 OFM cases published in four articles and 138 cases of SCFM published in five articles. Demographic and clinical data were extracted and analyzed, including age, sex, lesion location, size, duration, symptoms, clinical impression, treatment, and recurrence. Results: The mean age of OFM patients was 41 years, with a slight female predominance, most commonly affecting the gingiva. SCFM cases were more common in males, with a higher mean age of 52 years and frequent occurrence on the extremities and trunk. Both lesions were predominantly asymptomatic and managed by conservative excision. Due to its rare occurrence and nonspecific clinical presentation, both entities were frequently clinically misdiagnosed. Conclusions: In conclusion, this is the first study to directly compare OFM with SCFM and represents the largest series of OFM reported to date. The study provides new comparative insights into SCFM and OFM, highlighting differences in age, gender, lesion site, size, and symptomatology. SCFM predominantly affects older males on the extremities, whereas OFM occurs in younger females, mainly in the gingiva, with larger, sometimes symptomatic lesions, and with a very low recurrence rate.

Neurofibromatosis type 1 (NF1) is a prevalent neurocutaneous illness resulting from mutations in the NF1 gene, usually diagnosed according to clinical criteria set by the National Institutes of Health (NIH). These encompass café-au-lait macules, axillary freckling, Lisch nodules, ocular gliomas, osseous lesions, neurofibromas, and familial history. Atypical instances exhibiting partial or isolated characteristics, such as numerous cutaneous neurofibromas (cNFs) absent other classical manifestations, provide a diagnostic difficulty and may be little acknowledged in clinical environments. We describe a 47-year-old male with several soft, non-tender, pinkish-red papules and nodules dispersed throughout the face, torso, limbs, and back. A solitary café-au-lait macule measuring 3 x 2 cm was seen below the right breast, no axillary or inguinal freckling was observed, Lisch nodules were absent during ophthalmologic examination, and there was no pertinent family history. The histopathological examination of a skin lesion verified the diagnosis of cutaneous neurofibroma. According to the NIH guidelines, the patient did not satisfy the requirements for a conclusive diagnosis of NF1. This instance underscores the clinical intricacy of NF1 spectrum diseases and suggests the potential for mosaic NF1 or a minor phenotypic variation. The existence of several cNFs without systemic involvement undermines the adequacy of existing diagnostic paradigms, particularly in adults who exhibit no early-life signs. The psychosocial challenges linked to widespread cNF distribution highlight the necessity for a comprehensive assessment. Limitations encompass the lack of genetic testing, which would have facilitated the confirmation of the diagnosis and the assessment of probable mosaicism. Isolated cutaneous neurofibromas, devoid of other conventional NF1 characteristics, are an uncommon yet clinically pertinent manifestation. Clinicians must uphold a heightened level of suspicion for aberrant NF1 phenotypes and contemplate further examination, using molecular diagnostics where feasible. Reevaluating diagnostic criteria to include these polymorphisms is essential for prompt identification, effective care, and enhanced patient outcomes.