Combining Reflectance Confocal Microscopy, Optical Coherence Tomography and Ex-Vivo Fluorescence Confocal Microscopy for Margin Assessment in Basal Cell Carcinoma Excision.

INTRODUCTION: Recent developments of noninvasive, high-resolution imaging techniques, such as reflectance confocal microscopy (RCM) and optical coherence tomography (OCT), have enhanced skin cancer detection and precise tumor excision particularly in highly aggressive and poorly defined basal cell carcinomas (BCCs). OBJECTIVES: The aim of this pilot study is to assess the feasibility and reproducibility of a systematic clinical workflow combining noninvasive (RCM-OCT) and invasive fluorescence confocal microscopy (FCM) imaging modalities in pre- and intra-surgical evaluations of the lateral and deep margins of BCC. METHODS: Superficial incisions were made 2 mm beyond the clinical-dermoscopic BCC margins. Lateral margins were then explored with OCT and RCM. In positive margins, a further cut was made 2 mm distal from the previous. A final RCM/OCT-based double-negative margin was drawn around the entire perimeter of the lesion before referring to surgery. The freshly excised specimen was then examined with FCM (ex-vivo) for the evaluation of the deep margin. Histopathologic examination eventually confirmed margin involvement. RESULTS: The study included 22 lesions from 13 patients. At the end of the study, 146 margins-106 negative (73%) and 40 positive (27%) at RCM/OCT-were collected. The RCM/OCT margin evaluation showed an overall sensitivity of 100% and a specificity of 96.3%. The overall positive margins diagnostic accuracy was 98.2%. Reproducibility was evaluated on recorded images and the raters showed a substantial inter-observer agreement on both RCM (κ = 0.752) and OCT images (κ = 0.724). CONCLUSIONS: The combined RCM/OCT/FCM ex-vivo approach noninvasively facilitates the presurgical and intrasurgical lateral and deep margin assessment of poorly defined BCCs.

Wound Healing after Acellular Dermal Substitute Positioning in Dermato-Oncological Surgery: A Prospective Comparative Study.

BACKGROUND: MatriDerm and Integra are both widely used collagenic acellular dermal matrices (ADMs) in the surgical setting, with similar characteristics in terms of healing time and clinical indication. The aim of the present study is to compare the two ADMs in terms of clinical and histological results in the setting of dermato-oncological surgery. METHODS: Ten consecutive patients with medical indications to undergo surgical excision of skin cancers were treated with a 2-step procedure at our Dermatologic Surgery Unit. Immediately after tumor removal, both ADMs were positioned on the wound bed, one adjacent to the other. Closure through split-thickness skin grafting was performed after approximately 3 weeks. Conventional histology, immunostaining and ELISA assay were performed on cutaneous samples at different timepoints. RESULTS: No significant differences were detected in terms of either final clinical outcomes or in extracellular matrix content of the neoformed dermis. However, Matriderm was observed to induce scar retraction more frequently. In contrast, Integra was shown to carry higher infectious risk and to be more slowly reabsorbed into the wound bed. Sometimes foreign body-like granulomatous reactions were also observed, especially in Integra samples. CONCLUSIONS: Even in the presence of subtle differences between the ADMs, comparable global outcomes were demonstrated after dermato-oncological surgery.

Are Parapoxvirus zoonotic diseases doomed to remain neglected?

Parapoxvirus (PPV) infections are considered neglected zoonoses because their incidence is often unknown or greatly underestimated despite being endemic globally. Here, we report the comprehensive diagnostic workflow that led to the identification of two cases of persistent PPV infections. The results obtained underline the importance of adopting a "One Health" approach and cross-sectoral collaboration between human and veterinary medicine for precise aetiological diagnosis and correct management of patients affected by zoonotic diseases.

Cutaneous Melanoma Systematic Diagnostic Workflows and Integrated Reflectance Confocal Microscopy Assessed with a Retrospective, Comparative Longitudinal (2009-2018) Study.

BACKGROUND: The increasing global burden of melanoma demands efficient health services. Accurate early melanoma diagnosis improves prognosis. OBJECTIVES: To assess melanoma prevention strategies and a systematic diagnostic-therapeutical workflow (improved patient access and high-performance technology integration) and estimate cost savings. METHODS: Retrospective analysis of epidemiological data of an entire province over a 10-year period of all excised lesions suspicious for melanoma (melanoma or benign), registered according to excision location: reference hospital (DP) or other (NDP). A systematic diagnostic-therapeutical workflow, including direct patient access, primary care physician education and high-performance technology (reflectance confocal microscopy (RCM)) integration, was implemented. Impact was assessed with the number of lesions needed to excise (NNE). RESULTS: From 40,832 suspicious lesions excised, 7.5% (n = 3054) were melanoma. There was a 279% increase in the number of melanomas excised (n = 203 (2009) to n = 567 (2018)). Identification precision improved more than 100% (5.1% in 2009 to 12.0% in 2018). After RCM implementation, NNE decreased almost 3-fold at DP and by half at NDP. Overall NNE for DP was significantly lower (NNE = 8) than for NDP (NNE = 20), p < 0.001. Cost savings amounted to EUR 1,476,392.00. CONCLUSIONS: Melanoma prevention strategies combined with systematic diagnostic-therapeutical workflow reduced the ratio of nevi excised to identify each melanoma. Total costs may be reduced by as much as 37%.

In Vivo Melanoma Cell Morphology Reflects Molecular Signature and Tumor Aggressiveness.

Melanoma is the deadliest type of skin cancer characterized by high cellular heterogeneity, which contributes to therapy resistance and unpredictable disease outcome. Recently, by correlating reflectance confocal microscopy morphology with histopathological type, we identified four distinct melanoma subtypes: dendritic cell, round cell, dermal nest, and combined-type melanomas. In this study, each reflectance confocal microscopy melanoma subtype expressed a specific biomolecular profile and biological behavior in vitro. Markers of tumor aggressiveness, including Ki-67, MERTK, nestin, and stemness markers were highest in the most invasive combined-type and dermal nest melanomas than in dendritic cell and round cell melanomas. This was also confirmed in multicellular tumor spheroids. Transcriptomic analysis showed modulation of cancer progression-associated genes from dendritic cell to combined-type melanomas. The switch from E- to N-cadherin expression proved the epithelial-to-mesenchymal transition from dendritic cell to combined-type subtypes. The dermal nest melanoma was predominantly located in the dermis, as also shown in skin reconstructs. It displayed a unique behavior and a molecular profile associated with a high degree of aggressiveness. Altogether, our results show that each reflectance confocal microscopy melanoma subtype has a distinct biological and gene expression profile related to tumor aggressiveness, confirming that reflectance confocal microscopy can be a dependable tool for in vivo detection of different types of melanoma and for early diagnostic screening.

The Tensor Tympani Tendon: A Hypothetical Site of Origin of Congenital Cholesteatoma.

Multiple theories have been discussed about the etiopathogenesis of congenital middle ear cholesteatoma (CMEC) and its specific site of origin. The intraoperative identification of the precise location of the keratinous mass is important to guarantee its complete removal, in order to reduce the risk of recurrence. This study proposes the tensor tympani tendon (TTT) as a possible site of origin of CMEC. All CMECs treated between 2013 and 2019 were reviewed. Only Potsic stage I lesions were included. Preoperative radiologic images were compared to intraoperative findings. Three removed TTT were sent for histologic evaluation. Seven patients were included (M:F = 3:4). Preoperative CT images were classified as type A in 2 cases (28.6%) and type B in 5 cases (71.4%). At intraoperative evaluation all CMEC sacs were found pedunculated on the TTT. The histologic examinations confirmed the connection between the cholesteatomatous sac and the TTT. According to the correlation of imaging, intraoperative findings and histology, we proposed that the TTT could be the primary site from which CMEC originates.

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.

NTRK Gene Fusion Detection in Atypical Spitz Tumors.

Atypical Spitz tumors (AST) deviate from stereotypical Spitz nevi for one or more atypical features and are now regarded as an intermediate category of melanocytic tumors with uncertain malignant potential. Activating NTRK1/NTRK3 fusions elicit oncogenic events in Spitz lesions and are targetable with kinase inhibitors. However, their prevalence among ASTs and the optimal approach for their detection is yet to be determined. A series of 180 ASTs were screened with pan-TRK immunohistochemistry and the presence of NTRK fusions was confirmed using FISH, two different RNA-based NGS panels for solid tumors, and a specific real time RT-PCR panel. Overall, 26 ASTs showed pan-TRK immunostaining. NTRK1 fusions were detected in 15 of these cases showing cytoplasmic immunoreaction, whereas NTRK3 was detected in one case showing nuclear immunoreaction. Molecular tests resulted all positive in only two ASTs (included the NTRK3 translocated), RNA-based NGS and real time RT-PCR were both positive in three cases, and FISH and real time RT-PCR in another two cases. In seven ASTs NTRK1 fusions were detected only by FISH and in two cases only by real time RT-PCR. The frequency of NTRK fusions in ASTs is 9%, with a clear prevalence of NTRK1 compared to NTRK3 alterations. Pan-TRK immunohistochemistry is an excellent screening test. Confirmation of NTRK fusions may require the use of different molecular techniques.

Metabolomic Analysis of Actinic Keratosis and SCC Suggests a Grade-Independent Model of Squamous Cancerization.

Background-Actinic keratoses (AKs) are the most common sun-induced precancerous lesions that can progress to squamocellular carcinoma (SCC). Recently, the grade-independent association between AKs and SCC has been suggested; however, the molecular bases of this potential association have not been investigated. This study has assessed the metabolomic fingerprint of AK I, AK II, AK III and SCC using high resolution magic angle spinning (HR-MAS) nuclear magnetic resonance (NMR) spectroscopy in order to evaluate the hypothesis of grade-independent association between AK and SCC. Association between AKs and SCCs has also been evaluated by histopathology. Methods-Metabolomic data were obtained through HR-MAS NMR spectroscopy. The whole spectral profiles were analyzed through multivariate statistical analysis using MetaboAnalyst 5.0. Histologic examination was performed on sections stained with hematoxylin and eosin; statistical analysis was performed using STATA software version 14. Results-A group of 35 patients affected by AKs and/or SCCs and 10 healthy controls were enrolled for metabolomics analysis. Histopathological analysis was conducted on 170 specimens of SCCs and AKs (including the ones that underwent metabolomic analysis). SCCs and AK I were found to be significantly associated in terms of the content of some metabolites. Moreover, in the logistic regression model, the presence of parakeratosis in AKs appeared to be less frequently associated with SCCs, while AKs with hypertrophy had a two-fold higher risk of being associated with SCC. Conclusions-Our findings, derived from metabolomics and histopathological data, support the notion that AK I are different from healthy skin and share some different features with SCCs. This may further support the expanding notion that all AKs should be treated independently from their clinical appearance or histological grade because they may be associated with SCC.

Correlation between Autofluorescence Intensity and Histopathological Features in Non-Melanoma Skin Cancer: An Ex Vivo Study.

Non-melanoma skin cancer (NMSC) is the most common malignant tumor affecting fair-skinned people. Increasing incidence rates of NMSC have been reported worldwide, which is an important challenge in terms of public health management. Surgical excision with pre-operatively identified margins is one of the most common and effective treatment strategies. Incomplete tumor removal is associated with a very high risk of recurrence and re-excision. Biological tissues can absorb and re-emit specific light wave-lengths, detectable through spectrophotometric devices. Such a phenomenon is known as autofluorescence (AF). AF spectroscopy has been widely explored for non-invasive, early detection of NMSC as well as for evaluation of surgical margins before excision. Fluorescence-aided diagnosis is based on differences in spectral characteristics between healthy and neoplastic skin. Understanding the biological basis of such differences and correlating AF intensity to histological features could improve the diagnostic accuracy of skin fluorescence spectroscopy. The primary objective of the present pre-clinical ex vivo study is to investigate the correlation between the intensity of cutaneous AF and the histopathological features of NMSC. Ninety-eight lesions suggestive for NMSCs were radically excised from 75 patients (46 M; 29 F; mean age: 79 years). After removal, 115 specific reference points on lesions ("cases"; 59 on BBC, 53 on SCC and 3 on other lesions) and on peri-lesional healthy skin (controls; 115 healthy skin) were identified and marked through suture stitches. Such reference points were irradiated at 400-430 nm wavelength, and resulting emission AF spectra were acquired through spectrophotometry. For each case, AFIR (autofluorescence intensity ratio) was measured as the ratio between the number of photons emitted at a wavelength ranging between 450 and 700 nm (peak: 500 nm) in the healthy skin and that was captured in the pathological tissue. At the histological level, hyperkeratosis, neoangiogenesis, cellular atypia, epithelial thickening, fibrosis and elastosis were quantified by light microscopy and were assessed through a previously validated grading system. Statistical correlation between histologic variables and AFIR was calculated through linear regression. Spectrometric evaluation was performed on 230 (115 cases + 115 controls) reference points. The mean AFIR for BCC group was 4.5, while the mean AFIR for SCC group was 4.4 and the fluorescence peaks at 500 nm were approximately 4 times lower (hypo-fluorescent) in BCCs and in SCCs than in healthy skin. Histological variables significantly associated with alteration of AFIR were fibrosis and elastosis (p < 0.05), neoangiogenesis, hyperkeratosis and epithelial thickening. Cellular atypia was not significantly associated with alteration of AFIR. The intensity of fluorescence emission in neoplastic tissues was approximately 4 times lower than that in healthy tissues. Histopathological features such as hyperkeratosis, neoangiogenesis, fibrosis and elastosis are statistically associated with the decrease in AFIR. We hypothesize that such tissue alterations are among the possible biophysical and biochemical bases of difference in emission AF between neoplastic and healthy tissue. The results of the present evaluation highlighted the possible usefulness of autofluorescence as diagnostic, non-invasive and real-time tool for NMSCs.

ROS1 pattern of immunostaining in 11 cases of spitzoid tumour: comparison with histopathological, fluorescence in-situ hybridisation and next-generation sequencing analysis.

AIMS: Spitzoid tumours have been shown to harbour exclusive kinase fusions. Few studies have analysed substantial numbers of ROS1-rearranged lesions. The aim of the present study was to investigate also their immunohistochemical profile. METHODS AND RESULTS: Among a group of 35 spitzoid tumours, of which 34 were consecutively diagnosed in a 3-year period, we found 11 ROS1 cases that were immunohistochemically positive, from 10 patients, eight of whom were female and two of whom were male, and who were aged 3-52 years (median, 29 years); most lesions (eight) were localized on the lower extremities. Four patterns of immunostaining were observed: cytoplasmic granular diffuse (six cases), sparse cytoplasmic granules (three cases), paranuclear dots (one case), and nuclear (one case). Fluorescence in-situ hybridisation (FISH) analysis showed all cases to be rearranged (cut-off of >15%). RNA next-generation sequencing (NGS) analysis showed specific fusions of ROS1 in four cases: two with PWWP2A, one with PPFIBP1, and one with ZCCHC8. DNA NGS analysis showed in five cases, specific mutations of AKT, EGFR, NRAS, MYC, ALK, and KIT. ROS1 lesions belonged predominantly to the 'atypical Spitz tumour' group, and showed mainly a nested histological pattern. Interestingly, one patient developed two ROS1-positive lesions. CONCLUSIONS: Immunohistochemistry showed 100% sensitivity and specificity as compared with the FISH results, corresponding to ROS1 rearrangement in 31% of cases studied. These observations shed new light on the value of immunohistochemical evaluation of ROS1 in spitzoid tumours. ROS1 patterns of immunostaining probably reflect different subcellular localisations of ROS1 fusions, although no specific correlations were found in the cases studied. Immunohistochemistry and FISH were the most sensitive techniques for detecting ROS1 rearrangement in this subset of neoplasms.

NGS-Based Analysis of Atypical Deep Penetrating Nevi.

Deep penetrating nevi (DPNs) are rare melanocytic neoplasms consisting of pigmented spindled or epithelioid melanocytes with a distinctive wedge-shaped configuration showing activation of the WNT pathway, with unusual cyto-architectural features. It is unclear whether they show a distinct genomic profile associated with a diverse metastatic potential. We describe herein a cohort of 21 atypical DPNs analyzed by next-generation sequencing using the Ion AmpliSeq™ Comprehensive Cancer Panel. We found that ß-catenin exon 3 was mutated in 95% and MAP kinase pathway genes in 71% of the cases. Less frequent mutations were observed in HRAS (19%) and MAP2K1 (24%). Isocitrate dehydrogenases 1 (IDH1) mutations, including R132C, V178I, and S278L, were identified in 38% of cases and co-existed with BRAF/HRAS mutations. The only case with progressive nodal disease carried alterations in the ß-catenin pathway and mutations in IDH1 and NRAS (codon 61). By a comprehensive mutation analysis, we found low genetic heterogeneity and a lack of significant associations between specific gene mutations and histopathological features, despite atypical features. Whether the acquisition of an NRAS or IDH1 mutation in an atypical DPN may represent a molecular evolution implying a pathway to melanoma progression should be confirmed in a larger series.

Atypical fibroxanthoma and pleomorphic dermal sarcoma: A reappraisal.

BACKGROUND: Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) share clinical, pathological, immunohistochemical and molecular features, though PDS is associated with a more aggressive behavior. METHODS: We reviewed 71 tumors fulfilling criteria for AFX and PDS to further stratify their biological potential. RESULTS: Lesions were mainly located on the scalps of elderly men, and were often ulcerated. One case was necrotic, one showed vascular invasion, and one showed perineural invasion. Fifty-one tumors were limited to reticular dermis (71.8%), 20 invaded subcutaneous tissue, focally in 13 cases (18.3%), and diffusely in seven (9.9%). Subcutaneous invasion was present significantly more often in tumors showing predominantly spindle compared to pleomorphic/mixed cell morphology (P = 0.02). At a follow-up of 17-125 months, 4 cases recurred locally, 4, 6, 10 and 13 months after surgery; no metastases were observed. Three tumors were composed of spindle cells, and one of clear cells. Three cases had margins focally involved, while the fourth case had clear margins. CONCLUSION: Depth of invasion and state of margins are criteria predicting prognosis in AFX/PDS; in addition, spindle cell morphology seems to be related to a more infiltrative pattern of growth and to aggressiveness. Grouping these tumors on a morphologic base could help to clarify their different biological behavior.

Sebaceous Carcinoma of the Breast: Fact or Fiction? A Case Report and a Review of the Literature.

Introduction. Previously considered an exceedingly rare entity, sebaceous carcinoma of the breast is now regarded in the World Health Organization 2019 classification as a "special histopathological pattern" of invasive breast carcinoma of no special type. Case Description. In this article, we report the case of a fine needle aspiration cytology and the histopathological features of a breast carcinoma with clear-cut morphological features suggesting sebaceous differentiation, but showing no positive staining with the anti-adipophilin antibody. Conclusions. A morphologically clear-cut sebaceous differentiation is not invariably associated with adipophilin positivity; moreover, in breast carcinoma, adipophilin positivity does not automatically imply sebaceous differentiation. At present, immunomorphological evidence for the recognition of sebaceous carcinoma as a "special type" breast carcinoma subtype is too weak.

CSF1R Is Required for Differentiation and Migration of Langerhans Cells and Langerhans Cell Histiocytosis.

Langerhans cell histiocytosis (LCH) is a rare disorder characterized by tissue accumulation of CD1a+CD207+ LCH cells. In LCH, somatic mutations of the BRAF V600E gene have been detected in tissue LCH cells, bone marrow CD34+ hematopoietic stem cells, circulating CD14+ monocytes, and BDCA1+ myeloid dendritic cells (DC). Targeting BRAF V600E in clonal Langerhans cells (LC) and their precursors is a potential treatment option for patients whose tumors have the mutation. The development of mouse macrophages and LCs is regulated by the CSF1 receptor (CSF1R). In patients with diffuse-type tenosynovial giant cell tumors, CSF1R inhibition depletes tumor-associated macrophages (TAM) with therapeutic efficacy; however, CSF1R signaling in LCs and LCH has not been investigated. We found through IHC and flow cytometry that CSF1R is normally expressed on human CD1a+CD207+ LCs in the epidermis and stratified epithelia. LCs that were differentiated from CD14+ monocytes, BDCA1+ DCs, and CD34+ cord blood progenitors expressed CSF1R that was downregulated upon maturation. Immature LCs migrated toward CSF1, but not IL34. Administration of the c-FMS/CSF1R kinase inhibitors GW2580 and BLZ945 significantly reduced human LC migration. In LCH clinical samples, LCH cells (including BRAF V600E cells) and TAMs retained high expression of CSF1R. We also detected the presence of transcripts for its ligand, CSF1, but not IL34, in all tested LCH cases. CSF1R and CSF1 expression in LCH, and their role in LC migration and differentiation, suggests CSF1R signaling blockade as a candidate rational approach for treatment of LCH, including the BRAF V600E and wild-type forms of the disease.

Expression of calretinin in odontogenic keratocysts and basal cell carcinomas: A study of sporadic and Gorlin-Goltz syndrome-related cases.

Gorlin-Goltz syndrome (GGS), is an autosomal dominant inherited disorder related to germline mutation of PTCH1 gene, characterised by the presence of multiple developmental anomalies and tumours, mainly basal cell carcinomas (BCC) and odontogenic keratocysts (OKC). We analysed and compared the expression of calretinin in 16 sporadic OKCs, from 15 patients, and 12 syndromic OKCs from 11 patients; in 19 BCC's and 2 cutaneous keratocysts (CKC) belonging to 4 GGS patients, 15 sporadic BCCs and 3 steatocystomas (SC). Calretinin was negative in 10 of 12 syndromic OKCs, focally positive (<5% of cells) in 2; six sporadic OKCs were negative, 6 focally and 4 diffusely positive (p = .02, cases focally and diffusely positive vs. cases negative). All BCCs of 3 GGS patients were negative, the fourth patient presented two BCCs negative and 5 focally or diffusely positive; 7 sporadic BCCs were negative and 8 focally positive (p = NS). Two CKCs resulted negative in one GGS patient; 2 sporadic SCs were positive, and a third was negative. PTCH1 mutations produce an altered PTCH protein and an aberrant activation of Sonic hedgehog (SHH) pathway, leading to tumoral proliferation. It has been demonstrated that treatment of human foetal radial glia cells with SHH reduces, whereas the blockage of SHH increases calretinin expression. We found a lower expression of calretinin in syndromic OKCs compared to sporadic cases. Although calretinin's value in differential diagnosis between sporadic and syndromic tumours appears not crucial, our results shed light on the possible link between SHH dysfunction and calretinin expression in GGS-related tumours.

Clinical and Dermoscopic Factors for the Identification of Aggressive Histologic Subtypes of Basal Cell Carcinoma.

BACKGROUND: Infiltrative basal cell carcinoma (BCC) has a higher risk for post-surgical recurrence as compared to the most common low-aggressive superficial and nodular BCC. Independent diagnostic criteria for infiltrative BCC diagnosis have not been still defined. Improving the pre-surgical recognition of infiltrative BCC might significantly reduce the risk of incomplete excision and recurrence. OBJECTIVE: The aim of this study is to define clinical and dermoscopic criteria that can differentiate infiltrative BCC from the most common low-aggressive superficial and nodular BCC. METHODS: Clinical and dermoscopic images of infiltrative, superficial, and nodular BCC were retrospectively retrieved from our database and jointly evaluated by two experienced dermoscopists, blinded for the histologic subtype. Pairwise comparisons between the three histologic subtypes were performed and multivariable logistic regression models were constructed in order to define clinical and dermoscopic factors independently associated with each subtype. To validate our findings, two experienced dermoscopists not previously involved in the study were asked to evaluate clinical and dermoscopic images from an external dataset, guessing the proper BCC subtype between infiltrative, nodular and superficial, before and after being provided with the study results. RESULT: A total of 481 histopathologically proven BCCs (51.4% nodular, 33.9% superficial, and 14.8% infiltrative) were included. We found that infiltrative BCC mostly appeared on the head and neck as an amelanotic hypopigmented plaque or papule, displaying ulceration on dermoscopic examination, along with arborizing and fine superficial telangiectasia. Shiny white structures were also frequently observed. Multivariate regression analysis allowed us to define a clinical-dermoscopic profile of infiltrative BCC. CONCLUSIONS: We defined the clinical-dermoscopic profile of infiltrative BCC, allowing to differentiate this variant from superficial and nodular BCC. This will improve pre-surgical recognition of infiltrative forms, reducing the risk for post-surgical recurrence.

A case of extramedullary hematopoiesis presenting as hemorrhagic panniculitis and evolving in acute myeloid leukemia.

Extramedullary hematopoiesis (EMH) in adults is a rare event, usually associated with myeloid disorders, and can be the first sign of chronic myelomonocytic leukemia. We report a case of EMH presenting as a hemorrhagic panniculitis in a patient who did not apparently present any myeloid disorders. The patient received previous chemotherapy for mantle cell lymphoma localized to the large bowel and had been in complete remission for 3 years. The diagnosis of EMH was achieved after a deep incisional biopsy of a nodule from the thigh, and with pathological examination that included immunohistochemical studies. After a follow-up of 14 months, the patient developed an acute myeloid leukemia, classified as therapy-related myeloid neoplasm, according to the 2016 World Health Organization (WHO) classification of hematological malignancies. As shown by the rare cases described in literature, the presence of cutaneous EMH should always be a trigger for investigating the patient's hematological system; also, in our experience, a long follow-up is mandatory.