Accuracy of World Health Organisation-grade parameters (necrosis and mitotic activity) and foci of vascular invasion in predicting prognosis of papillary thyroid carcinoma. A case-control validation study.

AIMS: Tumour necrosis and/or increased mitoses define high-grade papillary thyroid carcinoma (PTC). It is unclear whether angioinvasion is prognostic for PTC. Cut-offs at five or more mitoses/2 mm2 and four or more angioinvasive foci have been empirically defined based upon data from all forms of aggressive non-anaplastic thyroid carcinomas. Performance of tumour necrosis, mitoses and vascular invasion in predicting distant metastases when specifically applied to PTC is undefined. METHODS: We analysed 50 consecutive PTC cases with distant metastases (DM-PTC): 16 synchronous and 34 metachronous. A total of 108 non-metastatic PTC (N-DM-PTC, 15.0-year median follow-up) were used as controls. Invasive encapsulated follicular variant PTC was excluded. Necrosis, mitoses and angioinvasion were quantified. Receiver operating characteristics (ROC) and area under the curve (AUC) analyses determined best sensitivity and specificity cut-offs predictive of distant metastases. RESULTS: Metastases correlated with necrosis (any extent = 43.8% all DM-PTC, 53.1% metachronous DM-PTC versus 5% N-DM-PTC; P < 0.001), mitoses (P < 0.001) and angioinvasion (P < 0.001). Mitoses at five or more per 2 mm2 was the best cut-off correlating with distant metastases: sensitivity/specificity 42.9%/97.2% all DM-PTC (AUC = 0.78), 18.8%/97.2% synchronous DM-PTC (AUC = 0.63), 54.6%/97.2% metachronous DM-PTC (AUC = 0.85). Angioinvasive foci at five or more was the best cut-off correlating with distant metastases: sensitivity/specificity 36.2%/91.7% all DM-PTC (AUC = 0.75), 25%/91.7% synchronous DM-PTC (AUC = 0.79) and 41.9%/91.7% metachronous DM-PTC (AUC = 0.73). Positive/negative predictive values (PPV/NPV) were: necrosis 22.6%/98.2%; five or more mitoses 32.3%/98.2%; five or more angioinvasive foci 11.8%/97.9%. After multivariable analysis, only necrosis and mitotic activity remained associated with DM-PTC. CONCLUSION: Our data strongly support PTC grading, statistically validating World Health Organisation (WHO) criteria to identify poor prognosis PTC. Angioinvasion is not an independent predictor of DM-PTC.

Medullary Thyroid Carcinomas Classified According to the International Medullary Carcinoma Grading System and a Surveillance, Epidemiology, and End Results-Based Metastatic Risk Score: A Correlation With Genetic Profile and Angioinvasion.

Due to the lack of a standardized tool for risk-based stratification, the International Medullary Carcinoma Grading System (IMTCGS) has been proposed for medullary thyroid carcinomas (MTCs) based on necrosis, mitosis, and Ki67. Similarly, a risk stratification study using the Surveillance, Epidemiology, and End Results (SEER) database highlighted significant differences in MTCs in terms of clinical-pathological variables. We aimed to validate both the IMTCGS and SEER-based risk table on 66 MTC cases, with special attention to angioinvasion and the genetic profile. We found a significant association between the IMTCGS and survival because patients classified as high-grade had a lower event-free survival probability. Angioinvasion was also found to be significantly correlated with metastasis and death. Applying the SEER-based risk table, patients classified either as intermediate- or high-risk had a lower survival rate than low-risk patients. In addition, high-grade IMTCGS cases had a higher average SEER-based risk score than low-grade cases. Moreover, when we explored angioinvasion in correlation with the SEER-based risk table, patients with angioinvasion had a higher average SEER-based score than patients without angioinvasion. Deep sequencing analysis found that 10 out of 20 genes frequently mutated in MTCs belonged to a specific functional class, namely chromatin organization, and function, which may be responsible for the MTC heterogeneity. In addition, the genetic signature identified 3 main clusters; cases belonging to cluster II displayed a significantly higher number of mutations and higher tumor mutational burden, suggesting increased genetic instability, but cluster I was associated with the highest number of negative events. In conclusion, we confirmed the prognostic performance of the IMTCGS and SEER-based risk score, showing that patients classified as high-grade had a lower event-free survival probability. We also underline that angioinvasion has a significant prognostic role, which has not been incorporated in previous risk scores.

Is reflectance confocal microscopy useful in the differential diagnosis of extra facial lentigo maligna? A retrospective multicentric case-control study.

BACKGROUND: Extra facial lentigo maligna (EF-LM) arises outside the head and neck area. EF-LM presents the classic histological features of lentigo maligna. The dermoscopic aspects of EF-LM have been poorly studied. OBJECTIVE: The primary aims of our study were to analyse and describe the clinical, dermoscopic and confocal microscopy features of a series of histologically confirmed EF-LM. METHOD: We conducted a retrospective and multicentric study. From our database, we selected 48 cases of thin melanomas on photodamaged skin with histological features of EF-LM of which clinical, dermoscopic and confocal microscopy images were available, and a control group of 45 lesions, that can be subjected to differential diagnosis such as solar lentigo, lichenoid keratosis, seborrheic keratosis and melanocytic nevi, of which dermoscopic and confocal microscope images were available. RESULTS: Extra facial lentigo maligna had a higher prevalence of lentigo-like pigment patterns, angulated lines and zigzag structures. At confocal microscopy, LM-EF cases showed a higher prevalence of pagetoid spreading, round cells, dendritic cells in the epidermis, atypical cells at the dermo-epidermal junction, dendritic cells at the junction, meshwork pattern and elastosis. Our study shows that reflectance confocal microscopy (RCM) has a sensitivity of 90% and a specificity of 97% for the differential diagnosis of this type of melanoma. CONCLUSIONS: Extra facial lentigo maligna does not have the classic dermoscopic features of superficial spreading melanoma, the most observed dermoscopic criteria are angulated lines and lentigo-like pigment patterns without lentigo-like border. RCM can be a valuable imaging tool for the evaluation of all those suspicion skin lesions at dermoscopy highlighting cellular atypia suggestive for melanoma.

Characteristics and management of skin cancers in very elderly patients: A real-world challenge for clinicians.

The increase life expectancy led to an expected increase in skin cancer incidence in older patients. Their treatment can require a complex decision-making process. Limited data are available on characteristics, management and outcome of skin tumours in nonagenarian and centenarian patients. The aim of our study was to describe epidemiology, clinical-pathological features and treatment strategies of skin cancers in a cohort of patients aged ≧95 years. A total of 116 patients ≧95 years of age presented for the evaluation of 225 skin lesions (mean of 1.94 lesions per patient). The mean age was 97.4 years, 57.8% were women. Most patients had an ECOG score of 3 (49.3%) or 4 (32%). Lesions were mainly located on the head and neck area (74.2%), upper (7.1%) and lower (6,2%) limbs. The majority of patients presented with non-melanoma skin cancers (183/225; 81.3%), 25/225 (11.1%) had actinic keratosis, 5 (2.2%) melanoma and 2 (0.9%) atypical fibroxanthoma. Forty-eight lesions (21.3%) were treated with surgery, 58 (25.8%) with radiotherapy. The management of 73 lesion (32.4%) was discussed at the multidisciplinary tumour board meeting. One patient died for the progression of a squamous cell carcinoma; 74 patients died for causes unrelated to skin tumours, 36 are still alive after a mean follow-up of 27.27 months. This cohort study confirms that age is not per se a contraindication for treatment of skin cancers in elderly patients. Our results support the importance of a patient-centred care approach that should take into consideration patient's preferences, comorbidities, compliance and possible adverse events.

Clinically unquestionable but histologically deceptive melanomas in acral skin grafts: PRAME confirms its role.

The aim of this study was to investigate the role of PRAME in reducing the risk of an underestimation of tumour margins, in a consecutive series of acral melanomas recurring on skin grafts.

What to Know About Biopsy Sampling and Pathology in Vasculitis?

PURPOSE OF REVIEW: To summarize the histologic findings of vasculitis, and to give some practical considerations on biopsy samples. RECENT FINDINGS: The larger use of imaging and the discoveries of serological markers in the diagnosis of vasculitis have increased the clinical recognition of these entities. Nevertheless, biopsy remains the gold standard for diagnosis in most cases. So far, biopsies are also useful to obtain information about prognosis and to guide a more specific treatment. In recent years, less invasive diagnostic approaches have become available, lowering the risks related to the procedure and permitting a definite diagnosis in most cases. Histological examination permits a definite diagnosis of vasculitis. However, the findings may be nonspecific if not evaluated in the proper clinical setting. The interaction between clinicians and pathologists is crucial to obtain a definite diagnosis.

PRAME expression in cellular neurothekeoma: A study of 11 cases.

BACKGROUND: Preferentially expressed antigen in melanoma (PRAME) has been widely investigated in the skin, mainly in melanocytic tumors, and constitutes an aid in differentiating benign from malignant lesions. Very few studies have been performed on non-melanocytic tumors. MATERIALS: We investigated the immunohistochemical expression of PRAME on a series of 11 neurothekeomas (NTKs), together with 3 cases of nerve sheath myxoma (NSM) and 1 case of plexiform fibrohistiocytic tumor (PFT), in order to evaluate the presence and usefulness of this marker in their differential diagnosis. RESULTS: PRAME was variably expressed in all cases of NTK, with moderate intensity in three cases and faint in the remaining cases; on the contrary, cases of NSM and PFT were negative. CONCLUSIONS: This study expands the entities of cutaneous non-melanocytic tumors expressing PRAME, and confirms that this marker is not restricted to malignant tumors. Expression of PRAME in NTK does not seem to be related to distinctive histopathologic features.

Papillary thyroid carcinoma with prominent myofibroblastic stromal component: clinicopathologic, immunohistochemical and next-generation sequencing study of seven cases.

Papillary thyroid carcinoma with desmoid-type fibromatosis or nodular fasciitis-like stroma is an extremely unusual and poorly understood subtype of papillary thyroid cancer. Although prior studies have demonstrated alterations in the Wnt/ß-catenin signaling pathway in some of these tumors, controversy still exists regarding the nature of the stromal spindle component. We have studied seven cases of papillary thyroid carcinoma with prominent myofibroblastic stroma, including six men and one woman aged 20-65 years (mean age = 44). All cases displayed areas consistent with conventional papillary thyroid carcinoma embedded in abundant myofibroblastic-like stroma. The myofibroblastic stroma in six cases resembled desmoid-type fibromatosis and in one case it more closely resembled nodular fasciitis. By immunohistochemical staining, the stromal spindle component showed positivity for SMA and low MIB1 proliferation index in all cases, and there was at least patchy strong nuclear positivity for beta-catenin in six/seven cases. Stains for cytokeratin AE1/AE3 and PAX8 were positive in the epithelial elements but negative in the stromal component. Next-generation sequencing was performed on six of seven cases. CTNNB1 gene mutations were identified in six/seven cases. The epithelial component showed BRAF mutations in two cases and an NRAS mutation in one case. The case with fasciitis-like stroma was negative for beta-catenin by sequencing and immunostaining as well as negative for USP6 gene rearrangement. Our findings indicate that papillary thyroid carcinoma with prominent myofibroblastic stroma may represent more than one category of lesions.

Alazami syndrome: the first case of papillary thyroid carcinoma.

Alazami syndrome (MIM#615071) is a rare developmental disorder caused by biallelic variants in the LARP7 gene. Hallmark features include short stature, global developmental delay, and distinctive facial features. To date, 23 patients from 11 families have been reported in the literature. Here we describe a 19-year-old man who, in association with the typical features of Alazami syndrome, was diagnosed at the age of 14 years with papillary thyroid carcinoma, harboring the somatic BRAF V600E mutation. Whole exome sequencing revealed two novel LARP7 variants in compound heterozygosity, whereas only common variants were detected in genes associated with familial nonmedullary thyroid cancer (MIM#188550). LARP7 acts as a tumor suppressor in breast and gastric cancer, and possibly, according to recent studies, in thyroid tumors. Since thyroid cancer is rare among children and adolescents, we hypothesize that the LARP7 variants identified in our patient are responsible for both Alazami syndrome and tumor susceptibility. We also provide an overview of the clinical findings in all Alazami syndrome patients reported to date and discuss the possible pathogenetic mechanism that may underlie this condition, including the role of LARP7 in tumor susceptibility.

Neck Melanoma: Clinical, Dermoscopic and Confocal Features.

BACKGROUND: The head and neck are considered one single anatomical unit. No data on clinical, dermoscopic and confocal aspects of neck melanoma are currently available. OBJECTIVES: To identify clinical, dermoscopic and confocal diagnostic features of neck melanomas. METHODS: Consecutive malignant (cases) and benign (controls) melanocytic skin lesions located on the neck, excised as suspected of being melanoma from March 2011 to February 2018, were retrospectively retrieved. Dermoscopic criteria of the 7-point checklist, integrated by other melanoma features (such as grey colour and irregular hyperpigmented areas) were assessed. Reflectance confocal microscopy (RCM) images were examined when available. RESULTS: 282 lesions located to the head and neck area were biopsied to rule out melanoma. Thirty-one out of 282 (11%) lesions were located on the neck: 21 melanomas and 10 naevi. Melanoma patients were older than patients with naevi (mean age: 60.4 vs. 37.9 years, p < 0.001). Neck melanomas were more frequently located on sun-damaged skin compared to naevi (76.2 vs. 30%, p = 0.02). Dermoscopically, neck melanomas were characterized by irregular dots/globules, grey colour and regression (76.2, 81 and 46.7% of cases) and showed criteria of lentigo maligna melanoma (LMM) in 52.4% of cases. Regression, grey colour, irregular hyperpigmented areas and criteria of LMM typified melanomas on sun-damaged skin, whereas tumours located on non-sun-damaged areas were often characterized by irregular pigmentation (blotches). RCM, implemented to dermoscopy, correctly diagnosed 10/12 melanomas and 3/5 naevi. CONCLUSION: Neck melanoma has peculiar clinical and dermoscopic aspects that could help clinicians to distinguish it from naevi and to diagnose melanoma earlier.

Angiosarcoma and anaplastic carcinoma of the thyroid are two distinct entities: a morphologic, immunohistochemical, and genetic study.

Angiosarcoma and anaplastic carcinoma are the most lethal neoplasms of the thyroid worldwide and share some similarities, which have led to a longstanding controversy on their etiopathological relationship. Thyroid angiosarcomas are characterized by vessel formation and an immunophenotype common to endothelial cells, while anaplastic carcinomas are partially or wholly composed of mesenchymal-like cells that have lost the morphologic and functional features of normal thyroid follicular cells. To investigate whether angiosarcomas represent the endothelial extreme of the differentiation spectrum of carcinomas or they are bona fide vascular neoplasms, we studied the clinico-morphologic and genetic characteristics of a series of 10 angiosarcomas and 22 anaplastic carcinomas. Immunohistochemically, among the endothelial markers, CD31 and ERG were the most consistently expressed in angiosarcomas. Among the markers of thyroid origin, PAX8 was the most reliable in anaplastic carcinomas, while TTF-1 reactivity was found in only 5% of anaplastic carcinomas and thyroglobulin was always negative. Pankeratin reacted with most angiosarcomas and anaplastic carcinomas and is therefore not useful in the differential diagnosis. Interestingly a mutated pattern of p53 immunostaining prompted a diagnosis of anaplastic carcinoma. To compare the genetic profile, we used the NGS approach to sequence hotspot regions within a panel of 57 genes. As a result, only a few mutations were found in angiosarcomas and all of them were single events (no TP53 or TERT mutation). On the other hand, anaplastic carcinomas were characterized by a higher number of mutations, and TP53 and TERT promoter mutations were the most frequent genetic alterations. The lack in angiosarcomas of the common mutations identified in anaplastic carcinomas supports a different genetic origin and strongly suggests that, in spite of a shared sarcomatous morphology and a similar clinical aggressiveness, angiosarcomas and anaplastic carcinomas rely on a completely different set of genetic alterations during their evolution.

PAX8-GLIS3 gene fusion is a pathognomonic genetic alteration of hyalinizing trabecular tumors of the thyroid.

The hyalinizing trabecular adenoma/tumor is a rare and poorly characterized follicular-derived thyroid neoplasm recently shown to harbor recurrent PAX8-GLIS1 or PAX8-GLIS3 gene fusions. Here we sought to define the repertoire of genetic alterations of hyalinizing trabecular tumors, and whether PAX8-GLIS3 fusions are pathognomonic for hyalinizing trabecular tumors. A discovery series of eight hyalinizing trabecular tumors was subjected to RNA-sequencing (n = 8), whole-exome sequencing (n = 3) or targeted massively parallel sequencing (n = 5). No recurrent somatic mutations or copy number alterations were identified in hyalinizing trabecular tumor, whereas RNA-sequencing revealed the presence of a recurrent genetic rearrangement involving PAX8 (2q14.1) and GLIS3 (9p24.2) genes in all cases. In this in-frame fusion gene, which comprised exons 1-2 of PAX8 and exons 3-11 of GLIS3, GLIS3 is likely placed under the regulation of PAX8. Reverse transcription RT-PCR and/or fluorescence in situ hybridization analyses of a validation series of 26 hyalinizing trabecular tumors revealed that the PAX8-GLIS3 gene fusion was present in all hyalinizing trabecular tumors (100%). No GLIS1 rearrangements were identified. Conversely, no PAX8-GLIS3 gene fusions were detected in a cohort of 237 control thyroid neoplasms, including 15 trabecular thyroid lesions highly resembling hyalinizing trabecular tumor from a morphological standpoint, as well as trabecular/solid follicular adenomas, solid/trabecular variants of papillary carcinoma, and Hurthle cell adenomas or carcinomas. Our data provide evidence to suggest that the PAX8-GLIS3 fusion is pathognomonic for hyalinizing trabecular tumors, and that the presence of the PAX8-GLIS3 fusion in thyroid neoplasms may be used as an ancillary marker for the diagnosis of hyalinizing trabecular tumor, thereby avoiding overtreatment in case of misdiagnoses with apparently similar malignant tumors.

Pigmented skin lesions displaying regression features: Dermoscopy and reflectance confocal microscopy criteria for diagnosis.

Melanomas and nevi displaying regression features can be difficult to differentiate. To describe reflectance confocal microscopy features in benign and malignant pigmented skin lesions characterized by regression features in dermoscopy. Observational retrospective study. Inclusion criteria were presence of dermoscopic features of regression; availability of clinical, dermoscopic and RCM imaging; definite histopathologic diagnosis. The study sample comprised 217 lesions; 108 (49.8%) melanomas and 109 were benign lesions, of which 102 (47.0%) nevi and 7 (3.2%) lichen planus-like keratosis (lplk). Patients with melanoma were significantly older than those with benign lesions (61.9 ± 15.4 vs 46.1 ± 14.8; P < 0.001) and a higher proportion of melanomas displayed dermoscopic regression structures in more than 50% of lesion surface (n = 83/108; 76.9%; P < 0.001). On RCM examination, pagetoid cells were significantly more reported in melanoma group, than in benign lesions (86.1% vs 59.6%; P < 0.001) and were more frequently widespread distributed (65.6% vs 20.0%; P < 0.001) and both dendritic and roundish (36.6% vs 15.4%; P < 0.001) in shape. Aspecific architecture at the dermo-epidermal junction (DEJ) was more commonly seen among melanomas than benign lesions (23.1% vs 11.9%; P = 0.002) with higher presence of dendritic and both dendritic and roundish atypical cells at the DEJ (28.7% vs 18.3% and 19.4% vs 3.7%; P < 0.001, respectively). Focal pagetoid infiltration and ringed or clod patterns were more commonly seen in benign lesion. In conclusion, the correct interpretation of regressing lesions remains a challenge, assessing carefully the extent and characteristics of architectural and cytologic atypia on RCM is an additional piece of the complex puzzle of melanoma diagnosis.

LATERAL NECK DISSECTION FOR AGGRESSIVE VARIANTS OF WELL-DIFFERENTIATED THYROID CANCER.

Objective: Well-differentiated thyroid cancer (WDTC) is characterized by favorable disease course and excellent survival. However, some histologic subtypes, known as aggressive histologic variants (AHVs), present a more aggressive behavior than conventional WDTC. The aim of this study was to evaluate the pattern of nodal involvement and factors influencing prognosis in N1b patients with AHVs. Methods: A multicentric retrospective analysis of patients who underwent therapeutic lateral neck dissection (ND) for WDTC between 1994 and 2015 was accomplished. AHVs included the following subtypes: tall cell, Hürtle cell, diffuse sclerosing, and poorly differentiated papillary thyroid cancer. Results: The study included a total of 352 N1b patients, 40 (11.4%) of whom had AHVs. AHVs present a similar distribution of positive nodes if compared with conventional WDTC. In AHV patients, 5-year overall survival (OS), disease-specific survival (DSS), locoregional control, and metastasis-free survival were 82.2%, 93.6%, 80.3%, and 87.3%, respectively. Advanced age (>55 years) was the only significant factor affecting survival (OS, P<.001; DSS, P = .011) in this group. In the AHV group, there were 9 (22.5%) recurrences; patients with regional recurrence and without distant metastases were effectively treated by surgery. Conclusion: The distribution of positive lymph nodes in case of AHVs is similar to that of conventional WDTC, with only level V at a relatively greater risk of harboring metastases in the former group. Survival outcomes in N1b patients with AHVs remain optimal. Total thyroidectomy, ND, and adjuvant radioiodine administration have been demonstrated to be effective treatments in the setting of AHVs. Abbreviations: AHV = aggressive histologic variant; DOD = died of disease; DSS = disease-specific survival; DSV = diffuse sclerosing variant; ETE = extrathyroidal extension; HCC = Hürthle cell carcinoma; LRC = locoregional control; LVI = lymphovascular invasion; MFS = metastasis-free survival; ND = neck dissection; NED = no evidence of disease; OS = overall survival; PDA = poorly differentiated areas; PTC = papillary thyroid carcinoma; RAI = radioiodine therapy; TCV = tall cell variant; WDTC = well-differentiated thyroid cancer.

RUNX2 expression in thyroid and breast cancer requires the cooperation of three non-redundant enhancers under the control of BRD4 and c-JUN.

Aberrant reactivation of embryonic pathways is a common feature of cancer. RUNX2 is a transcription factor crucial during embryogenesis that is aberrantly reactivated in many tumors, including thyroid and breast cancer, where it promotes aggressiveness and metastatic spreading. Currently, the mechanisms driving RUNX2 expression in cancer are still largely unknown. Here we showed that RUNX2 transcription in thyroid and breast cancer requires the cooperation of three distantly located enhancers (ENHs) brought together by chromatin three-dimensional looping. We showed that BRD4 controls RUNX2 by binding to the newly identified ENHs and we demonstrated that the anti-proliferative effects of bromodomain inhibitors (BETi) is associated with RUNX2 transcriptional repression. We demonstrated that each RUNX2 ENH is potentially controlled by a distinct set of TFs and we identified c-JUN as the principal pivot of this regulatory platform. We also observed that accumulation of genetic mutations within these elements correlates with metastatic behavior in human thyroid tumors. Finally, we identified RAINs, a novel family of ENH-associated long non-coding RNAs, transcribed from the identified RUNX2 regulatory unit. Our data provide a new model to explain how RUNX2 expression is reactivated in thyroid and breast cancer and how cancer-driving signaling pathways converge on the regulation of this gene.

Dermoscopy of syringocystadenoma papilliferum.

Syringocystadenoma papilliferum is a benign adnexal neoplasm frequently seen in association with other adnexal tumours. We report the dermoscopic features of three cases of syringocystadenoma papilliferum developing in naevus sebaceus. Clinically the lesions were characterised by exophytic papillary structures. Dermoscopically, polymorphous vessels were the prevalent feature.

Dermoscopy features of atypical fibroxanthoma: A multicenter study of the International Dermoscopy Society.

BACKGROUND/OBJECTIVES: Little is known about the dermoscopic features of atypical fibroxanthoma. METHODS: This was a case-control study. Atypical fibroxanthoma lesions were compared with a control group with non-melanoma skin cancer. RESULTS: Altogether 40 atypical fibroxanthoma were collected. Most developed in men (93%), appearing mainly as nodular (63%), amelanotic (93%) and ulcerated (78%) lesions. Most lesions were located on the scalp (55%) and the ears (13%). Dermoscopically, most atypical fibroxanthoma displayed red (83%) and white (70%) structureless areas and irregular linear vessels (43%). A series of features achieved statistical significance when comparing atypical fibroxanthoma with non-melanoma skin cancer. The presence of red and white structureless areas and white lines, and the absence of yellowish-white opaque scales, hairpin vessels and arborising vessels were predictive of atypical fibroxanthoma in univariate analysis. However, when squamous cell carcinoma was excluded from the analysis, none of the criteria achieved statistical significance. When basal cell carcinoma was excluded, three variables achieved statistical significance in predicting atypical fibroxanthoma: red, structureless areas, the absence of opaque yellowish-white scales and absence of white circles. CONCLUSIONS: Atypical fibroxanthomas seem to be barely distinguishable from basal cell carcinoma dermoscopically, but they are more easily distinguishable from a well to moderately differentiated squamous cell carcinoma. A histopathological examination is needed for the final diagnosis.