A case of intraepidermal Merkel cell carcinoma within squamous cell carcinoma in-situ: Merkel cell carcinoma in-situ?

We report a case of a 79-year-old Caucasian male who presented with a wrist lesion of combined intraepidermal Merkel cell carcinoma and squamous cell carcinoma in-situ. The two tumors were tightly admixed and distinct, and both were without any dermal or invasive components. No features of transition between the two tumors were seen. We suggest the term Merkel cell carcinoma in situ for tumors that demonstrate exclusive intraepidermal proliferation of neuroendocrine cells.     

Analysis of αv integrin protein expression in human eyelid and periorbital squamous cell carcinomas

Background: Alpha v integrins are receptors for many extracellular matrix (ECM) protein ligands, including latent transforming growth factor betas (TGFβs). Various studies in mice have shown that ablation of genes encoding αv integrin or TGFβ signaling pathway components leads to spontaneous squamous cell carcinomas (SCCs) in the conjunctiva and periocular skin. Here, we have analyzed patterns of αv integrin protein expression and TGFβ signaling in human eyelid and periorbital SCC samples. Methods: An anti‐αv integrin antibody was used to immunostain 19 eyelid and periorbital SCC samples. Additionally, tissue lysates from resected normal eyelid and SCC samples were analyzed by immunoblotting for αv integrin protein. Tumor sections were also immunostained with an antibody directed against Smad2, an intracellular signaling protein that is phosphorylated by TGFβ receptors. Results: Alpha v integrin protein was highly expressed in the invasive and less‐differentiated components of human SCCs. Lower levels of αv integrin protein were detected in more differentiated components of tumors, as well as in SCC in situ. Patterns of phosphorylated Smad2 immunoreactivity correlated with levels αv integrin expression. Conclusions: Alpha v integrin was expressed at robust levels in tumor cells representing less differentiated, more invasive components of SCC; by contrast, well‐differentiated cells as well as SCC in situ expressed low levels of αv integrin protein. Hsu A, Esmaeli B, Hayek B, Hossain MG, Shinder R, Lazar AJ, McCarty JH. Analysis of αv integrin protein expression in human eyelid and periorbital squamous cell carcinomas.     

Micronodular basal cell carcinoma: A distinct subtype? Relationship with nodular and infiltrative basal cell carcinomas

Micronodular basal cell carcinoma (BCC) may be more difficult to eradicate and prone to recurrence than nodular subtype. The aim of the study was to compare anatomical and histological characteristics of the basal cell carcinomas subtypes and the relationship of the micronodular BCC with other subtypes. Primary BCCs (n = 3074) were classified as superficial, nodular, micronodular, morpheic/infiltrative. The location was head/neck, limbs, chest/abdomen, back or genitals. Fifty‐one micronodular BCCs were matched randomly with nodular and infiltrative cases, by age, sex, and tumor site. A modified Clark level was used to classify the tumor depth. Micronodular, nodular and infiltrative BCC were prevalently located in the head/neck (P < 0.0001), while superficial in the other regions (P < 0.0001). The Clark level was comparable between micronodular and infiltrative BCC, while nodular BCC showed a more superficial level than micronodular (P < 0.001) and infiltrative (P < 0.001) BCC. No nodular BCC had level IV and only 37.3% level III, while 92% of both micronodular and infiltrative BCC were level III or IV. The percentage of level IV was 11.8% and 25.5% in micronodular and infiltrative BCC, respectively. In the mid‐face/periauricular region, 95.5% of micronodular and 100% of infiltrative cases of were level III or IV, compared to 50% of nodular BCC (P < 0.001). The Clark level of nodular subtype was higher for BCC of mid‐face/periauricular than other regions (P < 0.05). It can be concluded that micronodular BCC shows intermediate characteristics compared with nodular and infiltrative subtypes but appears to have a specific individuality making it a distinct subtype.     

Are actinic keratoses really squamous cell cancer? How do we know if they would become malignant?

Actinic keratosis (AK) is a very common skin disease caused by chronic sun exposure. AKs have historically been characterized as being “precancerous” or “premalignant.” It is true that these lesions do not possess metastatic potential, because they are confined to the epidermis, but it is not accurate to deem them “premalignant.” AK qualifies as a malignant neoplasm, because it also fulfills criteria for malignancy in classic pathology, namely, the capability, or potential, to kill by either destruction of tissue locally or by metastasis widely. In this context, AK is considered now by many a carcinoma in situ and can persist or progress to invasive squamous cell carcinoma (iSCC), which rarely metastasizes. Through this controversy, which speaks to an issue we have been debating for at least a century, we should like to start a constructive debate to reach a unanimous conclusion considering the various theories and points of view in the literature.     

Are infantile seborrheic and atopic dermatitis clinical variants of the same disease?

BACKGROUND: The relationship between infantile seborrheic dermatitis (ISD) and infantile atopic dermatitis (IAD) is controversial. METHODS: Ninety-six children aged 2-12 months diagnosed with atopic dermatitis and a comparable control group of healthy children were evaluated. Demographic data, personal history of ISD and personal or family history of atopy was considered in both groups. RESULTS: A personal history of ISD was found in 49% of IAD cases and in 17% of controls (P < 0.05). CONCLUSIONS: Our result and those of the literature do not demonstrate a relationship between ISD and IAD. However, a number of cases of AD have an ISD-like clinical picture. It is probable that ISD is a syndrome and not a disease.     

Are new variants of psoriasis therapy (IL-17 inhibitors) safe?

Psoriasis is a chronic, recurrent, inflammatory, and proliferative skin disease. Its etiology has not yet been fully assessed, but undoubtedly it is a multifaceted disease. The key role in its pathomechanism is played by genetic, immunologic, and environmental factors and stress. If traditional methods of psoriasis treatment (phototherapy, methotrexate, retinoids, cyclosporine A) fail, we reach for the following biopharmaceuticals – infliximab, etanercept, adalimumab, or ustekinumab. However, genetic engineering progress discovers new possibilities – the pending clinical trials involve IL-17, IL-23 antagonists, PDE4 and -3 and -1. Psoriasis etiopathogenesis mainly involves the IL-17A, IL-17F, and IL-17A/F subtypes, which affect the keratinocytes. The biological therapy molecularly oriented with the antagonists of interleukin 17 is based mainly on the influence onto the cytokine in the manner that prevents it from binding with the receptor. Three biopharmaceuticals are currently under third phase studies: two fully humanized antibodies neutralizing IL-17 – ixekizumab and secukinumab, and one human monoclonal antibody, brodalumab. The below work will be devoted to the analysis of possible undesirable symptoms, which were observed during the studies. We will try to review the latest literature concerning the most important clinical trials conducted in many centers.     

Differentiating squamous cell carcinoma from keratoacanthoma using histopathological criteria. Is it possible? A study of 296 cases

BACKGROUND: Squamous cell carcinoma (SCC) and keratoacanthoma (KA) are sometimes difficult to distinguish by histopathological examination, since cytological features are similar in both tumors. Distinctive criteria - mainly architectural - have therefore been proposed as an aid in diagnosis. OBJECTIVE: The purpose of this study was to evaluate the reliability of some of the criteria used to make a distinction between SCC and KA. METHODS: 296 fully excised tumors previously classified as SCC or KA were randomized and examined independently by two examiners. Fourteen criteria, mainly based on the architecture of the tumors, were determined on the 262 slides for which a consensual diagnosis was made. RESULTS: No single criterion was sufficiently sensitive and specific to allow a clear-cut differential diagnosis. The 5 most relevant criteria were epithelial lip, sharp outline between tumor and stroma in favor of KA and ulceration, numerous mitoses and marked pleomorphism/ anaplasia in favor of SCC. Intraepithelial polymorphonuclear abscesses, intraepithelial elastic fibers, parakeratosis and dyskeratosis and extension more lateral than downward were not distinctive criteria, although they are considered as classic distinctive features. CONCLUSION: Many of the criteria commonly used for the differential diagnosis of SCC and KA are not reliable. The combination of the 5 most useful criteria does not significantly increase the specificity or sensitivity of the histological diagnosis in difficult cases. Atypical or difficult cases should therefore be considered and treated as SCC, since a clear-cut distinction is not possible even with the aid of the most relevant criteria.     

Are all seborrheic keratoses benign? Review of the typical lesion and its variants

BACKGROUND: Seborrheic keratosis (SK) is one of the more common benign epidermal neoplasms seen in adult and middle-aged patients. OBJECTIVE: As little is written in the literature about the variants of SK, this article aims to categorize and discuss the different subtypes and their important associations. METHODS: An in-depth literature search using OVID Medline and PubMed was conducted to classify the various subtypes of SK. Clinical variants were photographed and used to help document the subtypes. The pathology is described for each. RESULTS: Six subtypes of SK were identified: dermatosis papulosa nigra, stucco keratosis, inverted follicular keratosis, large cell acanthoma, lichenoid keratosis, and flat seborrheic keratosis. Although the etiology and pathogenesis of SKs are still largely debatable, several underlying mechanisms and contributing factors have been identified. All subtypes represent benign lesions, and treatment is usually done for cosmetic reasons. Several of the subtypes may act as cutaneous markers for internal malignancy and should be monitored closely for any atypical changes. CONCLUSION: Although all subtypes of SK are benign, their association with other malignant lesions and ability to serve as cutaneous markers of internal malignancy emphasize the importance of correctly identifying all variants.     

Rate of growth—A novel surrogate marker for high‐risk cutaneous squamous cell carcinoma? A case report and review of the literature

Cutaneous squamous cell carcinoma (cSCC) is one of the most common nonmelanoma skin cancer worldwilde, with a more invasive growth pattern and higher potential to metastatize than basal cell carcinoma. Although several risk factors have been linked to a high metastatic potential of cSCC, no widely accepted classification system for this common subtype of cancer exists. Herein we report an emblematic case of rapidly growing and metastatic cSCC and discuss the rate of growth of the tumour (ROG) as novel prognostic high risk surrogate marker.     

Basal cell carcinoma or not? Histological variants and mimics of the most common cutaneous malignancy

Basal cell carcinomas are the most common cutaneous malignancy encountered by dermatologists. Although most basal cell carcinomas have typical features and are easily diagnosed histologically, some basal cell carcinomas are problematic. Because the best evidence suggests that basal cell carcinomas arise from primitive stem cells that differentiate along follicular lines, it is not uncommon that this tumor may resemble and be confused with a variety of benign and malignant follicular and sweat gland tumors. This article will focus on some common and rare histological variants that may produce confusion, as well as salient features that will allow the correct diagnosis to be made.