Machine learning for classification of cutaneous sebaceous neoplasms: implementing decision tree model using cytological and architectural features.

BACKGROUND: This observational study aims to describe and compare histopathological, architectural, and nuclear characteristics of sebaceous lesions and utilized these characteristics to develop a predictive classification approach using machine learning algorithms. METHODS: This cross-sectional study was conducted on Iranian patients with sebaceous tumors from two hospitals between March 2015 and March 2019. Pathology slides were reviewed by two pathologists and the architectural and cytological attributes were recorded. Multiple decision tree models were trained using 5-fold cross validation to determine the most important predictor variables and to develop a simple prediction model. RESULTS: This study assessed the characteristics of 123 sebaceous tumors. Histopathological findings, including pagetoid appearance, neurovascular invasion, atypical mitosis, extensive necrotic area, poor cell differentiation, and non-lobular tumor growth pattern, as well as nuclear features, including highly irregular nuclear contour, and large nuclear size were exclusively observed in carcinomatous tumors. Among non-carcinomatous lesions, some sebaceoma and sebaceous adenoma cases had features like high mitotic activity, which can be misleading and complicate diagnosis. Based on multiple decision tree models, the five most critical variables for lesion categorization were identified as: basaloid cell count, peripheral basaloid cell layers, tumor margin, nuclear size, and chromatin. CONCLUSIONS: This study implemented a machine learning modeling approach to help optimally categorize sebaceous lesions based on architectural and nuclear features. However, studies of larger sample sizes are needed to ensure the accuracy of our suggested predictive model.

High expression of Talin-1 is associated with tumor progression and recurrence in melanoma skin cancer patients.

BACKGROUND: Talin-1 as a component of multi-protein adhesion complexes plays a role in tumor formation and migration in various malignancies. This study investigated Talin-1 in protein levels as a potential prognosis biomarker in skin tumors. METHODS: Talin-1 was evaluated in 106 skin cancer (33 melanomas and 73 non-melanomas skin cancer (NMSC)) and 11 normal skin formalin-fixed paraffin-embedded (FFPE) tissue samples using immunohistochemical technique on tissue microarrays (TMAs). The association between the expression of Talin-1 and clinicopathological parameters, as well as survival outcomes, were assessed. RESULTS: Our findings from data minings through bioinformatics tools indicated dysregulation of Talin-1 in mRNA levels for skin cancer samples. In addition, there was a statistically significant difference in Talin-1 expression in terms of intensity of staining, percentage of positive tumor cells, and H-score in melanoma tissues compared to NMSC (P = 0.001, P < 0.001, and P < 0.001, respectively). Moreover, high cytoplasmic expression of Talin-1 was found to be associated with significantly advanced stages (P = 0.024), lymphovascular invasion (P = 0.023), and recurrence (P = 0.006) in melanoma cancer tissues. Our results on NMSC showed a statistically significant association between high intensity of staining and the poor differentiation (P = 0.044). No significant associations were observed between Talin-1 expression levels and survival outcomes of melanoma and NMSC patients. CONCLUSION: Our observations showed that higher expression of Talin1 in protein level may be significantly associated with more aggressive tumor behavior and advanced disease in patients with skin cancer. However, further studies are required to find the mechanism of action of Talin-1 in skin cancers.

Whole transcriptome-based skin virome profiling in typical epidermodysplasia verruciformis reveals α-, ß-, and γ-HPV infections.

HPVs are DNA viruses include approximately 450 types that are classified into 5 genera (α-, ß-, γ-, µ-, and ν-HPV). The γ- and ß-HPVs are present in low copy numbers in healthy individuals; however, in patients with an inborn error of immunity, certain species of ß-HPVs can cause epidermodysplasia verruciformis (EV), manifesting as recalcitrant cutaneous warts and skin cancer. EV presents as either typical or atypical. Manifestations of typical EV are limited to the skin and are caused by abnormal keratinocyte-intrinsic immunity to ß-HPVs due to pathogenic sequence variants in TMC6, TMC8, or CIB1. We applied a transcriptome-based computational pipeline, VirPy, to RNA extracted from normal-appearing skin and wart samples of patients with typical EV to explore the viral and human genetic determinants. In 26 patients, 9 distinct biallelic mutations were detected in TMC6, TMC8, and CIB1, 7 of which are previously unreported to our knowledge. Additionally, 20 different HPV species, including 3 α-HPVs, 16 ß-HPVs, and 1 γ-HPV, were detected, 8 of which are reported here for the first time to our knowledge in patients with EV (ß-HPV-37, -47, -80, -151, and -159; α-HPV-2 and -57; and γ-HPV-128). This study expands the TMC6, TMC8, and CIB1 sequence variant spectrum and implicates new HPV subtypes in the pathogenesis of typical EV.

Ichthyosis follicularis syndromes in patients with mutations in GJB2.

Ichthyosis follicularis (IF) manifests as generalized spiny follicular projections found in syndromic diseases secondary to SREBF1 and MBTPS2 mutations. We sought the genetic cause of IF in two distinct families from a cohort of 180 patients with ichthyosis. In Family 1, the proband (Patient 1) presented with IF, bilateral sensorineural hearing loss and punctate palmoplantar keratoderma. Using DNA from peripheral blood lymphocytes, two compound heterozygous mutations, c.526A>G and c.35delG, were discovered in GJB2. In Family 2, the proband (Patient 2) presented with a previously unreported IF phenotype in the context of keratitis-ichthyosis-deafness syndrome, and whole-exome sequencing found a de novo heterozygous mutation, c.148G>A in GJB2. Histopathology was consistent with porokeratotic eccrine ostial and dermal duct naevus (PEODDN) and IF in Patients 1 and 2, respectively. Our findings add to the clinical and histopathological spectrum of IF and emphasize the association of PEODDN-like entities with GJB2 variants.

Cutaneous granular cell tumor: A case series, review, and update.

Background: Granular cell tumor (GCT) or Abrikossoff's tumor is an uncommon neuro-derived tumor in which Schwann cells are found and express S-100 protein. Often, it is a benign lesion. Histopathologically, there are granular cell infiltrations through the entire dermis without necrosis which are periodic acid Schiff (PAS) stain positive and reactive with S-100. The aim of this study is the clinicopathological evaluation of GCT. Material and Methods: In this paper, we described the experience of 6 patients with a GCT in different locations (4 cases in the skin and 2 cases in the mucosa), for example, a case with a tumor in the abdomen and a keloidal-like presentation with a highly sclerotic pattern (an uncommon pathological feature). Another case developed a lesion secondary to physical trauma. Result: In one case, the presence of a lesion in the lower lip associated with actinic damage secondary to chronic sun exposure resulted in misdiagnosis with actinic cheilitis and squamous cell carcinoma. Conclusion: Histopathologically, there were granular cell infiltrations through the entire dermis without necrosis which are PAS-positive and reactive with S-100.

Prevalence and Main Determinants of BRAF V600E Mutation in Dysplastic and Congenital Nevi.

BACKGROUND & OBJECTIVE: Predicting the transformation of dysplastic or congenital nevi into malignant lesions results in a significant increase in the survival of patients. Some specific gene mutations have been reported to be very helpful in this regard. Therefore, this study aimed to evaluate the prevalence of BRAF V600E mutation in dysplastic and congenital nevi. METHODS: This cross-sectional study was conducted on patients with congenital (n=30) or dysplastic (n=30) nevi. For genomic analysis, the BRAF gene mutation (V600E) was evaluated using the real-time polymerase chain reaction. RESULTS: The prevalence of BRAF gene (V600E) mutation was found as 1 case (3.3%) in congenital and 8 cases (26.7%) in dysplastic nevi indicating the higher prevalence of this mutation in patients with dysplastic nevi (P=0.026). Moreover, in the dysplastic nevi group, the presence of BRAF gene mutation (V600E) showed a significant relationship with the severity of dysplasia as the mutation rate was 25% in mild cases, in comparison with 54.5% in moderate dysplasia cases (P=0.009). CONCLUSION: According to the results, 3.3% of the patients with congenital nevi and 26.7% of the subjects with dysplastic nevi were positive for BRAF V600E mutation. Furthermore, the severity of dysplasia could have a positive relationship with the presence of the mutation.

Coexistence of Neonatal Lupus Erythematous and Sturge-Weber Syndrome.

Neonatal lupus erythematous (NLE) is a rare condition presented by lupus dermatitis shortly after birth or later following sun exposure. Sturge-Weber syndrome (SWS) is also an uncommon congenital condition characterized by extensive capillary malformation and ophthalmic and/or neurologic involvement. Here, we describe the first case of coexistence of NLE and SWS which posed a significant diagnostic challenge to clinicians.

Increasing the expression of programmed death ligand 2 (PD-L2) but not 4-1BB ligand in colorectal cancer cells.

Immune checkpoint (ICP) molecules modulate the immune response by either inducing or preventing T cell activation. Over-expression of some ICPs on malignant cells has been shown to regulate anti-tumor immune responses. We aimed to investigate the expression levels of two immune checkpoint molecules which have not been studied extensively in patients with colorectal cancer (CRC). Programmed Death Ligand 2 (co-inhibitory) and 4-1BB ligand (co-stimulatory) were assessed in tumor tissues of CRC patients compared to the adjacent normal tissues. Following tissue excision during surgical operation from 21 CRC patients, RNA extraction, cDNA synthesis and semi-quantitative real-time PCR were done for measuring the expressions of PD-L2 and 4-1BBL genes. In protein level, indirect immunohistochemistery (IHC) was performed on tissue sections. We revealed that PD-L2 was expressed in about 81% CRCs and insignificantly correlated with the tumor differentiation grade. Although a 3.25-fold change in the gene expression of PD-L2 was found in tumor tissues compared to the adjacent normal tissues (P = 0.005), but decreased level of 4-1BBL in counterpart tissues was not significant. Our results were confirmed by IHC for PDL-2 (P = 0.02) and 4-1BBL, however it was not statistically significant for the latter one. Although not significant, we could find an association between the elevated expression of PD-L2 and the tumor differentiation grade. Increased expression of negative regulator of the anti-tumor immune responses like PD-L2, as a prominent way of tumor escape, can be considered for cancer immunotherapy approaches in CRC patients using blocking monoclonal antibodies.

Basal cell carcinoma associated with erythema ab igne.

Erythema ab igne is a skin condition mainly caused by heat exposure. Erythema ab igne usually follows a favorable prognosis. However, it may increase the risk of developing cutaneous malignancy in the involved skin. Being familiar with the type of cutaneous malignancies that may arise in the site of erythema ab igne is considerably important. To our knowledge, this letter presents the first case that shows the association between erythema ab igne and basal cell carcinoma.

New diagnostic markers in basal cell carcinoma.

BACKGROUND: The clinical significance of plasma lipoprotein levels in the diagnosis and prognosis of certain diseases is known fact. Some studies have reported different and contradictory levels of blood lipoproteins in cancer patients. Therefore, we decided to compare lipid profiles in patients with basal cell carcinoma (BCC) and healthy individuals. MATERIALS AND METHODS: In this case-control study, lipid biomarkers in blood plasma of 64 patients with BCC compared with biomarkers in 64 healthy subjects. According to including criteria's both group selected. 5 cc blood samples taken after 8-12 h of fasting. Ultimately, the diagnosis of biopsy samples confirmed by the dermatopathologist. The information data entered into the PASS II software and then characterized by a descriptive and analytical statistics of the lipid profile. The role of the related factors was assessed by two sample t-test power analysis. RESULTS: In this research, mean age of patient group and the healthy one was 67.13 ± 11.33 and 64.31 ± 6.98, respectively. The average amount of triglyceride, cholesterol, high density lipoprotein (HDL) and low density lipoprotein in the BCC patients were 147.97 ± 87.11 mg/dl, 188.25 ± 38.90 mg/dl, 61.98 ± 18.61 mg/dl and 95.98 ± 31.69 mg/dl, respectively, whereas these amounts in the control group were 137.34 ± 61.41 mg/dl, 173.22 ± 38.79 mg/dl, 42.34 ± 7.83 mg/dl and 106.44 ± 35.17 mg/dl, respectively. There were statistically significant differences between cholesterol and HDL in patients with BCC and healthy controls, respectively (P = 0.030) (P < 0.001). CONCLUSION: It seems that changes in lipid profile can help as a diagnostic marker for detecting cancer like BCC. Although this change could be different in lipid markers and also among different types of cancer.

An enlarging scaly plaque localized on the previous keloid of the chest.

Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma (CTCL). It may arise rapidly in a scar or keloid, presumably due to a long-standing proliferative state or autoimmune theory. There should be a low threshold for performing a skin biopsy if unusual lesions develop at those sites.

Low Expression of Occludin in the Melanoma Patient.

BACKGROUND & OBJECTIVE: Malignant melanoma is the fatal cutaneous neoplasm which is curable by the early diagnosis. The expression of occludin protein which is an integral membrane protein is altered in an epithelial-to-mesenchymal transition. Although, recent studies provide sufficient evidence supporting the functional importance of occludin in cancer, the prognostic significance of occludin expression levels in melanoma remains obscure. The aim of this study was to determine occludin expression level and its correlation with clinicopathological features of the patients with melanoma. METHODS: The occludin mRNA level was compared between paraffin-embedded tissues of 40 patients with melanoma and 10 subjects with normal skin. The quality and quantity of the RNA was determined and occludin expression level was measured using Real-time PCR and ∆∆CT computational technique. RESULTS: The occludin mRNA level reduced five-fold in the melanoma patients compared to the control group (P=0.000). No significant difference was observed between male and female cases (P=0.533). No significant correlation was observed between occludin mRNA level, mitotic count (P=0.252), and Breslow levels (P=0.171). CONCLUSION: We can conclude that down-regulation of occludin expression in the patients with melanoma is a hallmark of cancer progression and it might be used as a prognostic factor. No significant correlation was found between occludin gene expression and clinicopathological characteristics including Clark level, Breslow staging, mitotic count, age and gender (P<0.05).

Folliculotropic Mycosis Fungoides: Clinical and Histologic Features in Five Patients.

BACKGROUND: Alopecia can be a manifestation of mycosis fungoides (MF); however, the prevalence is unknown. AIMS: We sought to describe the clinicopathologic presentation of alopecia in patients with diagnosis of MF. METHODS: A retrospective analysis of patients with biopsy-proven MF, who were evaluated at our cancer center from 2002 to 2012, was performed to identify patients with alopecia. RESULTS: Five patients with alopecia were identified from reviewing of 157 patients with MF. The male:female ratio was 3:2, and the mean age of patients was 42.8 years. Two of these patients showed patchy hair loss on scalp which was clinically identical to alopecia areata. In remaining three patients, hair loss was seen in areas of MF lesions, and epidermal changes consisted of patch- and plaque-type lesions of MF, tumors, and follicular lesions (follicular MF) were also present. In two of these patients, lymphadenopathy without any visceral involvement was detected. CONCLUSIONS: Alopecia was observed in 5 (3.18%) patients with MF, which makes it a rare finding, which included alopecia areata-like patchy loss in 2 and alopecia within MF lesions in 3.

A New Subtype of Lichen Planopilaris Affecting Vellus Hairs and Clinically Mimicking Androgenetic Alopecia.

BACKGROUND: Lichen planopilaris (LPP) is a follicular variant of lichen planus. A new subtype of LPP mimicking androgenetic alopecia (AGA) may be misdiagnosed. Inappropriate medical therapy or hair transplantation may exacerbate this subtype. OBJECTIVE: To introduce clinicopathologic findings of a new subtype of LPP that selectively affects vellus hair in the pattern of AGA. MATERIALS AND METHODS: In a cross-sectional study, 433 (66.6%) men and 217 (33.4%) women with alopecia who were candidates of medical treatment or hair transplantation were included. Gross and microscopic attributes of their diseases were investigated. RESULTS: Among the total of 650 patients, 58 (8.9%; 95% confidence interval, 6.7%-11.1%) patients, including 52 women and 6 men, had LPP. We identified a distinct category of LPP presenting with diffuse hair loss in the pattern of AGA with predominant terminal hair, significant decrease in vellus hair, and minute punctuate scars in histopathology. Vellus hair follicles were the main sites of involvement. Perifollicular fibrosis and mild fibrosis with lichenoid lymphocytic infiltration around infundibular area of vellus hair follicles were present. CONCLUSION: There is a new form of LPP with clinical features similar to AGA. This form is histopathologically similar to LPP but selectively affects vellus hair follicles.

Validity of trichoscopy in the diagnosis of primary cicatricial alopecias.

BACKGROUND: There are limited data on the validity of dermatoscopy in primary cicatricial alopecias (PCAs) and its subtypes, including lichen planopilaris and discoid lupus erythematosus. Trichoscopic features of PCAs, their prevalence, and validity were evaluated in this study. METHODS: One hundred patients with PCA underwent dermatoscopy. Biopsy specimens were obtained after the site was marked with a dermatoscope. The control group comprised 100 patients with non-cicatricial alopecia and 100 normal individuals. Finally, the prevalence, sensitivity, and specificity of trichoscopic features were evaluated using SPSS and Stata software. RESULTS: The absence of follicular opening, perifollicular scale, and presence of one scarring pattern or white patch were sensitive and specific patterns in the trichoscopy of PCAs. The presence of tortuous branching vessels and follicular keratotic plugging was 100% specific for a diagnosis of discoid lupus erythematosus. CONCLUSIONS: Some trichoscopic features can help a dermatologist to differentiate between non-cicatricial alopecia and PCA. Moreover, a group of dermatoscopic features can be helpful in the diagnosis of PCA subtypes.

Nevus sebaceus: a clinicopathological study of 168 cases and review of the literature.

BACKGROUND: Nevus sebaceus is a hamartoma composed of abnormal epidermal and dermal components with clinical and histopathological features that change with aging. Prophylactic excision of the lesion was advised historically considering its potential for giving rise to malignant tumors. However, whether early prophylactic excision should be performed has been questioned recently as most of the tumors have been found to be benign in origin. METHODS: The histopathologic features of 168 patients with nevus sebaceus were reviewed to determine the frequency of different histologic features as well as associated neoplastic growths. RESULTS: Acanthosis, papillomatosis, and basal layer pigmentation were the most frequent findings. Hyperplastic changes of the sebaceous glands became obvious during the second decade and were present in 60% of the specimens from individuals older than 20. Inflammatory infiltrate was almost invariably present. Skin adnexal changes were frequently noted, including sebaceous gland hyperplasia (93.5%) and primitive hair follicles (76.8%). In 88.5% of scalp lesions, markedly decreased terminal hair was observed. Ectopic apocrine glands were present in 55.4% of specimens, while 24.4% showed anomalous ductal sweat gland structures resembling eccrine hyperplasia. Neoplastic changes were detected in nine cases, including four trichoblastomas, three tricholemmomas, and two syringocystadenoma papilliferums. CONCLUSION: Development of malignancies in sebaceus nevi is a rare phenomenon, and decision for excision of the lesion should be made after thorough evaluation of the pros and cons.

The expression of MMP-2 and Ki-67 in head and neck melanoma, and their correlation with clinic-pathologic indices.

OBJECTIVE: Melanoma is an aggressive tumor with propensity for early metastasis and poor prognosis with delayed diagnosis. Matrix metalloproteinase-2 (MMP-2) is involved in degradation of extra-cellular matrix proteins and tumor progression. Ki-67 is a predictor of tumor proliferation activity but its prognostic significance in melanoma is controversial. In this study, the prognostic value of MMP-2 and Ki-67 via immuno-staining in head and neck melanoma is investigated. MATERIAL AND METHODS: A retrospective analysis of 24 consecutive primary melanoma samples was performed. All samples were stained with monoclonal MMP-2 and Ki-67 antibodies. Two independent investigators evaluated the stained sections. The reactive cells were considered positive regardless of the staining intensity and reported as percentage. RESULTS: A strong correlation between MMP-2 expression, Breslow tumor thickness, and Clark level of invasion was observed (r = 0.85, P < 0.0001 and r = 0.84, P < 0.0001, respectively). A significant positive correlation was observed between MMP-2 expression and number of lymph node involved (r = 0.55, P value 0.005). MMP-2 over expression (>50%) was an independent predictor of lymph node involvement (OR: 2.1, P value: 0.01). No significant association was observed between Ki-67 expression and Breslow tumor thickness, Clark level, or lymph node involvement. CONCLUSION: MMP-2 expression correlates with tumor thickness in melanoma and is an independent predictive factor for lymph node involvement.

Epidermal nevus syndrome and dysplatic kidney disease.

Epidermal nevus syndrome is a rare congenital disorder, characterized by epidermal nevi and multiple organ involvement. Multicystic kidney disease has been very rarely reported in this syndrome. Here is the report of a boy presented with multiple epidermal nevi, cardiac anomaly, seizure attack, hemi hypertrophy, and multicystic dysplastic kidney complicated with Wilms' tumor. According to this association, it is suggested to search for dysplastic kidney disease in patients with neurocutaneous disorders.