Folliculotropism in Actinic Keratoses in Patients not Responding to Treatments: A Pilot Study.

Dear Editor, Actinic keratoses (AK) have a high prevalence in the general population, with greater rates in Caucasian patients after the fourth and fifth decades of life (37.5-60.0%) (1,2). Standard histopathologic reporting of AKs does not provide information on the presence of atypical keratinocytes extending to the hair follicle, also defined as folliculotropism (FLC). Commonly, atypical cells in AKs do not present FLC, but this feature can be observed in bowenoid AKs with full-thickness epidermal atypia (3,4). FLC has been considered a possible element enhancing the chances of a progression toward invasive SCC (iSCC). Fernandez-Figueras et al. (3) reported that the depth of FLC in AKs was correlated with the invasiveness of associated iSCC. Pandey et al. (5) reported a positive association between AKs with FLC and history of invasive cutaneous cancer or melanoma, more often in men at an older age. The role of FLC in cutaneous melanoma is still debated, but it is considered a parameter that may correlate with treatment response in lentigo maligna and disease progression or recurrences in invasive tumors (6,7). These studies draw particular attention to the potential role of hair bulge compartment stem cells in favoring tumor progression through the expression of adhesion molecules, cytokines, and growth factor receptors (8). Aks are known to have a high recurrence rate after topical treatment (1). The risk of evolution to an iSCC is not completely clear, but it has been estimated to be around 0.6% at 12 months and up to 2.5% at 48 months (1,3,7). Considering the possible progression and the heavy burden of AK treatments, including the economic burden, it is imperative to focus on histopathologic features associated with treatment failure. The aim of this preliminary study was to assess the histopathologic features, specifically FLC, of AK samples from patients considered "non-responders" to specific topical treatments. A secondary endpoint was to assess the clinical/dermoscopic features. Patients were considered "non-responders" if the lesions persisted after two alternated completed cycles of treatments with ingenol mebutate, imiquimod, diclofenac 3%, or 5-fluoruracil. Patients with a positive history of immunosuppression or genetic diseases were excluded. The study was approved by the local Ethics Committee. Slides of AKs diagnosed at the Laboratory of Dermatopathology, University of Bologna, Italy from January 2016 to October 2018 were reviewed by two dermatopathologists (CM, PAF). 155 "non-responder" AKs of five main histopathologic subtypes were included, classified from grade I to III according to the Roewert-Huber classification (9) (Table 1). The proliferative and atrophic histopathologic subtypes of AKs were detected in 33.6% and 30.4% samples, respectively. FLC was observed in 75.3% of the cases, subdivided into two categories, periadnexal (48.9%) and intraadnexal (26.4%). Periadnexal FLC was detected in 31.0% of atrophic and in 50.3% of proliferative AKs, while intraadnexal FLC was found in 48.7% and 29.2%, respectively (Figure 1, a, b). At dermoscopy, most lesions had been classified as grade I or II (38.8% and 45.8%), and only 15.4% as grade III, showing an unexpected non-response to treatment according to the dermoscopic criteria. In contrast, almost half of the AKs were classified as grade III at histology, revealing a discrepancy between the dermoscopic grading and histological findings in a majority of cases (77.4%) (Figure 2, c, d). Furthermore, atrophic and proliferative AKs accounted for 64.0% of total cases, and these are the variants associated with a higher probability of evolution toward an iSCC (10). The clinical/histological discrepancy has already been reported in the literature (9) and may represent a misleading factor for treatment choice and outcomes. We believe that a comparative analysis with dermoscopy and histology should be performed in non-responding AKs, in order to choose the best therapeutic option. In fact, some superficial treatments (such as cryotherapy) may not provide a good response in deep hair follicles (4). We also suggest encouraging greater focus on FLC and its description in pathology reports. This is a preliminary observational study, but it reinforces the need to further larger clinical studies investigating the role of specific histopathologic parameters in AKs, including FLC, that may correlate with treatment outcomes.

The Histopathologic Evaluation of Diagnostic Procedures in Nail Melanoma.

INTRODUCTION: The diagnostic delay in nail melanoma (NM) has been repeatedly emphasized. It may be related to both clinical misinterpretations and to errors in the bioptic procedure. OBJECTIVES: To assess the efficacy of histopathologic examination in different diagnostic biopsies in NM. METHODS: We retrospectively investigated the diagnostic procedures and histopathologic specimens referred to the Laboratory of Dermatopathology for the clinical suspicion of NM from January 2006 to January 2016. RESULTS: Eighty-six nail histopathologic specimens were analyzed consisting in 60 longitudinal, 23 punch and 3 tangential biopsies. A diagnosis of NM was performed in 20 cases, benign melanocytic activation in 51 cases and melanocytic nevi in 15 patients. Longitudinal and tangential biopsy were diagnostic in all cases, regardless of the clinical suspicion. Nail matrix punch biopsy instead was not diagnostic in most of the cases (13/23 specimens). CONCLUSIONS: In the presence of an NM clinical suspicion, longitudinal biopsy is recommended (lateral or median) because it provides exhaustive information on the characteristics of melanocytes morphology and distribution in all the components of the nail unit. Tangential biopsy, recently encouraged by expert authors due to the optimal surgical outcome, in our experience gives incomplete information on tumor extension. Punch matrix biopsy gives limited evidence in the diagnosis of NM.

Alopecia in Patients with Collagen VI-Related Myopathies: A Novel/Unrecognized Scalp Phenotype.

Collagen VI-related myopathies are characterized by severe muscle involvement and skin involvement (keratosis pilaris and impaired healing with the development of abnormal scars, especially keloids). Scalp involvement and hair loss have not been reported among cutaneous changes associated with collagen VI mutations. The aim of this study is to describe the clinical, trichoscopic, and histological findings of the scalp changes in patients affected by COL VI mutations and to estimate their prevalence. Patients with Ullrich congenital muscular dystrophy were enrolled and underwent clinical and trichoscopic examinations and a scalp biopsy for histopathology. Five patients were enrolled, and all complained of hair loss and scalp itching. One patient showed yellow interfollicular scales with erythema and dilated, branched vessels, and the histological findings were suggestive of scalp psoriasis. Two patients presented with scarring alopecia patches on the vertex area, and they were histologically diagnosed with folliculitis decalvans. The last two patients presented with scaling and hair thinning, but they were both diagnosed with folliculitis and perifolliculitis. Ten more patients answered to a "scalp involvement questionnaire", and six of them confirmed to have or have had scalp disorders and/or itching. Scalp involvement can be associated with COL VI mutations and should be investigated.

Digital Ulcers: Multidisciplinary Approach and Dermatological Management.

INTRODUCTION: Digital ulcers represent a current public health issue, due to the relevant difficulties in their management and their tendency to become chronic, non-healing lesions. OBJECTIVES: Our case series represents an opportunity to discuss the main comorbidities of digital ulcers and to present an evidence-based treatment protocol that has proved highly effective in our clinical practice. METHODS: We collected the clinical data about clinical features, associated diseases and diagnostic therapeutical procedures of 28 patients with digital ulcers referred to our Wound Care Service at S. Orsola-Malpighi Hospital. RESULTS: Digital ulcers were divided into 5 categories, based on the causative agent: peripheral artery disease: 5/16 females and 4/12 males, diabetes-associated wounds: 2/16 females and 1/12 males, mixed wounds: 4/12 males, pressure wounds: 3/16 females and 2/12 males, and immune-mediated diseases associated with wounds: 6/16 females and 1/12 males. Each group received specific management, based on the characteristics of the ulcer and the underlying comorbidities. CONCLUSIONS: The clinical evaluation of digital wounds requires a thorough knowledge of their aetiopathogenesis. A multidisciplinary approach is necessary to achieve a precise diagnosis and correct treatment.