The clinical and histopathological features of herpes zoster (HZ) are usually straightforward. Atypical histological presentations, in the absence of the classical viral cytopathic changes, are well ...documented and can make the diagnosis of HZ extremely difficult. Herein, we review the existing literature on atypical cutaneous histological manifestations of the disease, with emphasis on the subtle clues, use of immunohistochemistry, and potential pitfalls.
Tumid lupus erythematosus (TLE) has been the subject of heated debate regarding its correct nosographic classification. The definition of TLE has changed over time, varying according to the different ...studies performed. In this review, we address the initial definition of TLE, the changes that have taken place in the understanding of TLE, and its placement within the classification of cutaneous lupus erythematosus (CLE), with a focus on clinical, histopathological, immunophenotypical, and differential diagnosis aspects.
Folliculosebaceous cystic hamartoma (FSCH) is an uncommon hamartoma that usually presents on the central face area of adults as an asymptomatic, solitary dome-shaped or pedunculated papule. We report ...a case of a 35-year-old female who presented with six-months history of skin lesions on her labia majora. Histological findings included cystically dilated hair follicles with branching epithelial strands and interconnecting sebaceous gland consistent with the diagnosis of FSCH. The genital variant of FSCH was first described in 1998 and since then only six cases have been reported in the literature. We aim to increase awareness of this rare presentation due to the significant psychological implications and the risk of misdiagnosis.
A dermal interstitial lymphocytic infiltrate may represent a diagnostic challenge, particularly if the clinical history is not provided. We present three cases within the histological spectrum of ...morphea in which the immunohistochemical marker CD34 was helpful in confirming the diagnosis.
In recent years, particular interest has developed in molecular biology applied to the field of dermatopathology, with a focus on nevi of the Spitz spectrum. From 2014 onwards, an increasing number ...of papers have been published to classify, stratify, and correctly frame molecular alterations, including kinase fusions. In this paper, we try to synthesize the knowledge gained in this area so far. In December 2023, we searched Medline and Scopus for case reports and case series, narrative and systematic reviews, meta-analyses, observational studies-either longitudinal or historical, case series, and case reports published in English in the last 15 years using the keywords spitzoid neoplasms, kinase fusions, ALK, ROS1, NTRK (1-2-3), MET, RET, MAP3K8, and RAF1. ALK-rearranged Spitz tumors and ROS-1-rearranged tumors are among the most studied and characterized entities in the literature, in an attempt (although not always successful) to correlate histopathological features with the probable molecular driver alteration. NTRK-, RET-, and MET-rearranged Spitz tumors present another studied and characterized entity, with several rearrangements described but as of yet incomplete information about their prognostic significance. Furthermore, although rarer, rearrangements of serine-threonine kinases such as BRAF, RAF1, and MAP3K8 have also been described, but more cases with more detailed information about possible histopathological alterations, mechanisms of etiopathogenesis, and also prognosis are needed. The knowledge of molecular drivers is of great interest in the field of melanocytic diagnostics, and it is important to consider that in addition to immunohistochemistry, molecular techniques such as FISH, PCR, and/or NGS are essential to confirm and classify the different patterns of mutation. Future studies with large case series and molecular sequencing techniques are needed to allow for a more complete and comprehensive understanding of the role of fusion kinases in the spitzoid tumor family.
Abstract A 51-year-old woman was referred to our department with a mildly itchy persistent rash that had started 3 years earlier on the back of her thighs, leaving pale skin as it progressed. She ...noted worsening of the rash during winter months. There was a history of psychological stress preceding the onset of the rash. Clinical examination revealed bilateral symmetrical annular hypopigmented patches with erythematous and slightly scaly raised edges. Symmetrical patches of depigmentation were also seen on her forearms. An incisional biopsy from the left posterior thigh, including the hypopigmented centre and adjacent erythematous rim, revealed unremarkable epidermis corresponding to the hypopigmentation, while the advancing edge showed interface changes with a bandlike lymphohistiocytic infiltrate and prominent lymphocytic exocytosis. The lymphocytes were positive for pan T-cell markers (CD2, CD3, CD5, CD7), with relatively equal CD4 and CD8 populations. melan-A indicated reduced density of melanocytes. There was no evidence of clonality on T-cell receptor (TCR) gene rearrangement studies. Punch biopsy from a depigmented patch on the right forearm was unremarkable on haematoxylin and eosin sections. However, melan-A indicated that the epidermis was completely devoid of melanocytes. The diagnosis of inflammatory vitiligo with raised borders (IVRB) was made. IVRB is a rare subtype of vitiligo that typically presents with a raised erythematous, scaly and pruritic edge surrounding depigmented patches. Differentiating IVRB from hypopigmented mycosis fungoides can be challenging, both clinically and histologically, due to the prominent lichenoid infiltrate with epidermotropism and the predominance of CD8+ lymphocytes that can be found in both. Helpful clues include the characteristic erythematous border, as well as lack of clonality on TCR gene rearrangement studies in IVRB (Gomez-Moyano E, Vera-Casaño A, Gamero AH et al. Inflammatory vitiligo or hypopigmented mycosis fungoides? J Pediatr Hematol Oncol 2010; 32: 338–9). Melanocytes and epidermal melanin are more likely to be preserved in hypopigmented mycosis fungoides El-Darouti MA, Marzouk S, Azzam O et al. Vitiligo vs. hypopigmented mycosis fungoides (histopathological and immunohistochemical study, univariate analysis). Eur J Dermatol 2006; 16: 17–22. Clinicopathological correlation is crucial to make the distinction.
Abstract A 51-year-old woman was referred to our department with a mildly itchy persistent rash that had started 3 years earlier on the back of her thighs, leaving pale skin as it progressed. She ...noted worsening of the rash during winter months. There was a history of psychological stress preceding the onset of the rash. Clinical examination revealed bilateral symmetrical annular hypopigmented patches with erythematous and slightly scaly raised edges. Symmetrical patches of depigmentation were also seen on her forearms. An incisional biopsy from the left posterior thigh, including the hypopigmented centre and adjacent erythematous rim, revealed unremarkable epidermis corresponding to the hypopigmentation, while the advancing edge showed interface changes with a bandlike lymphohistiocytic infiltrate and prominent lymphocytic exocytosis. The lymphocytes were positive for pan T-cell markers (CD2, CD3, CD5, CD7), with relatively equal CD4 and CD8 populations. Melan-A indicated reduced density of melanocytes. There was no evidence of clonality on T-cell receptor (TCR) gene rearrangement studies. Punch biopsy from a depigmented patch on the right forearm was unremarkable on haematoxylin and eosin sections. However, melan-A indicated that the epidermis was completely devoid of melanocytes. The diagnosis of inflammatory vitiligo with raised borders (IVRB) was made. IVRB is a rare subtype of vitiligo that typically presents with a raised erythematous, scaly and pruritic edge surrounding depigmented patches. Differentiating IVRB from hypopigmented mycosis fungoides can be challenging, both clinically and histologically, due to the prominent lichenoid infiltrate with epidermotropism and the predominance of CD8+ lymphocytes that can be found in both. Helpful clues include the characteristic erythematous border, as well as lack of clonality on TCR gene rearrangement studies in IVRB (Gomez-Moyano E, Vera-Casaño A, Gamero AH et al. Inflammatory vitiligo or hypopigmented mycosis fungoides? J Pediatr Hematol Oncol 2010; 32: 338–9). Melanocytes and epidermal melanin are more likely to be preserved in hypopigmented mycosis fungoides El-Darouti MA, Marzouk S, Azzam O et al. Vitiligo vs. hypopigmented mycosis fungoides (histopathological and immunohistochemical study, univariate analysis). Eur J Dermatol 2006; 16: 17–22. Clinicopathological correlation is crucial to make the distinction.
Abstract The current World Health Organization classification of skin tumours (5th edition) indicates that melanocytic tumours of the Spitz pathway can be defined by mutually exclusive oncogenic ...drivers, including HRAS-activating mutations or kinase fusions. Accordingly, the term ‘spitzoid’ has been suggested for tumours that show morphological features of Spitz tumours but lack these defining molecular aberrations. Such neoplasms harbouring BRAF or NRAS mutations include a subtype of melanomas with confirmed risk of local recurrence and metastasis. In contrast, a recent study described a subset of Spitz-looking neoplasms with BRAF mutations and insufficient criteria for melanoma (Zhao J, Benton S, Zhang B et al. Benign and intermediate-grade melanocytic tumours with BRAF mutations and Spitzoid morphology. Am J Surg Pathol 2022; 46: 476–85). The term BRAF mutated and morphologically spitzoid naevi/tumours (BAMS) was proposed for such lesions. We present a series of four cases of BAMS. The patients ranged in age from 3 to 40 years; three were male and one was female. The clinical history varied from new growing moles to change within long-standing lesions, congenital in one instance. One lesion was submitted with the query of halo naevus. Anatomical sites included the abdomen, pubis, right buttock and left upper back. In one of our cases the clinical appearance, including starburst pattern on dermoscopy, was very suggestive of a pigmented Spitz naevus. All cases showed a predominantly epithelioid cytomorphology with accompanying melanophages. The cytoplasmic pigment was prominent in three cases. Three of the neoplasms were compound, with evidence of maturation with depth. The case described clinically as a changing congenital lesion had a mild degree of cytological atypia, a single superficial mitosis and focal PReferentially expressed Antigen in MElanoma positivity. In this case there was bridging of nests and lamellar fibroplasia, indicating overlapping features with Clark dysplastic naevus. Three cases had Kamino bodies. Immunostaining for BRAF V600E was positive in all cases. Overall, the histological findings in our cohort are in concordance with those reported by Zhao et al. Interestingly, BRAF mutations were also identified in another study of ‘Spitz naevi’, likely representing BAMS (Fullen DR, Poynter JN, Lowe L et al. BRAF and NRAS mutations in spitzoid melanocytic lesions. Mod Pathol 2006; 19: 1324–32). Further studies are necessary to characterize the BAMS group, including long-term follow-up. Recognition of this group of tumours is important to avoid melanoma overdiagnosis in the advent of ancillary immunohistochemistry and molecular testing in determining melanocytic lineage in day-to-day practice.
A 64-year-old man with a known history of psoriasis was under regular clinical and reflectance confocal microscopy follow-up for a biopsy-proven lentigo maligna on his right forehead. Five years ...after the initial diagnosis the lesion gradually disappeared with no concurrent effective treatment. Spontaneous resolution is reported in various skin tumours but to our knowledge, this phenomenon has not been previously described in lentigo maligna.
