Lymphoplasmocytic plaque in children: A report of an atypical location.

Lymphoplasmocytic plaque in children (LPC) is a rare and distinctive skin disorder primarily affecting the pediatric population. Characterized by its unique histopathological features, the condition manifests as well-defined plaques with a predominance of lymphocytes and plasma cells infiltrating the dermis. Despite its limited prevalence, recognizing this entity is crucial for accurate diagnosis and appropriate management of affected patients. We report the case of a 10-year-old male presenting with LPC in the extensor surface of the upper arm, a rarely reported location, treated with both topical and intralesional corticosteroids resulting in partial improvement.

Basal cell carcinomas of the scalp after radiotherapy for tinea capitis: Clinicopathological study in a case series of 96 patients with analysis of 427 tumours.

BACKGROUND/OBJECTIVES: Low-dose X-ray radiotherapy to treat tinea capitis during childhood is a well-known risk factor for scalp basal cell carcinomas (BCCs). Post-radiotherapy BCCs are often multiple, and it has been suggested that they display more aggressive features. Our main objective was to study the clinicopathological aspects of post-radiotherapy BCCs to evaluate their biological behaviour and identify features that may differ from other BCCs. METHODS: We performed an observational, retrospective study assessing multiple clinical and pathological characteristics of patients with post-radiotherapy BCCs. RESULTS: We studied 96 patients with 427 post-radiotherapy scalp BCCs. Post-radiotherapy BCCs were often multiple (median of 4 lesions/patient, ranging from 1 to 54). Significant comorbidities included a high incidence of thyroid disease and meningiomas. Recurrences were observed in 23% of patients, but there may be confounding factors, such as referral bias, heterogenous treatment modalities and occurrence of new tumours due to field effect. We found a high incidence of infundibulocystic BCCs (in 14.6% of patients and corresponding to 5.4% of the total number of tumours), trichoblastomas (5.2%) and neurofibromas of the scalp (10%). CONCLUSIONS: This study is consistent with the occurrence of multiple lesions (sometimes numerous) and a relatively high tendency for recurrence in post-radiotherapy BCCs, as suggested by previous studies. We also found a high incidence of the infundibulocystic variant and a higher risk of follicular tumours and neurofibromas, which suggests that radiotherapy may influence the type of differentiation of BCCs and contribute to induce neoplasms of different cell lines.

Erythematous brownish plaques with an annular configuration.

Granuloma annulare (GA) and cutaneous sarcoidosis show clinicopathological overlap and they are also aetiopathogenically related. Given the similarities of sarcoidal GA and sarcoidosis, and the reports of association of sarcoidal GA with systemic sarcoidosis, this diagnosis should prompt further investigation to exclude systemic involvement. Being aware of the subtle histopathological clues is of the utmost importance for an accurate diagnosis of this rare variant, but correlation with the clinical setting and use of ancillary investigations are also warranted to confidently exclude sarcoidosis.

Diffuse dermal angiomatosis: a rare cause of painful ulceration in renal insufficiency.

Diffuse dermal angiomatosis is a rare, benign, reactive cutaneous vascular proliferation that has been reported in the context of end-stage renal failure and can rarely be associated with arteriovenous fistulas. We report a striking clinical resolution following prompt diagnosis and subsequent arteriovenous fistula reversal. This case further demonstrates that accurate diagnosis is particularly rewarding since correct therapeutic approach can be curative.

Basal Cell Carcinomas After Radiotherapy Show More Frequent Follicular Differentiation Than Tumors From Sun-Exposed Areas: Immunohistochemical Study With a Special Focus on Infundibulocystic Basal Cell Carcinoma.

ABSTRACT: Patients submitted to radiotherapy for tinea capitis in childhood have an increased incidence of scalp basal cell carcinomas (BCCs) but also of other neoplasms, namely, follicular tumors. In a cohort of such patients, we also found a high incidence of infundibulocystic BCCs, an otherwise rare variant. We thus hypothesized that postradiotherapy BCCs could be more prone to display follicular differentiation. We compared the histological and immunohistochemical features of postradiotherapy BCCs [both conventional (16 cases) and infundibulocystic (16 cases)] with those of BCCs arising in sun-exposed areas (16 cases), using markers of follicular differentiation (PHLDA-1, CK15, CD34, ß-catenin, and calretinin). Postradiotherapy BCCs showed slightly higher tendency for infundibular and/or trichilemmal differentiation than BCCs from sun-exposed areas (37.5% vs. 18.8%), but this difference was not statistically significant. Nevertheless, infundibulocystic BCCs showed more frequent expression of PHLDA-1 and stronger cytoplasmic expression of CK15 compared with the other lesions. In addition, CD34 highlighted a characteristic meshwork of stromal cells surrounding the epithelial component in all infundibulocystic BCCs, in contrast to the other postradiotherapy BCCs and UV-related BCCs, in which 78.1% were negative or only focally positive. In conclusion, our study suggests a tendency for more frequent follicular differentiation in postradiotherapy BCCs compared with BCCs from sun-exposed areas. In addition, the immunohistochemical study confirms previous data from the literature regarding infundibulocystic BCCs (higher CK15 and PHLDA-1 expression) and shows a distinctive stromal positivity for CD34 that has not been previously acknowledged in these tumors.

Basal cell carcinomas of the scalp after radiotherapy for tinea capitis in childhood: A genetic and epigenetic study with comparison with basal cell carcinomas evolving in chronically sun-exposed areas.

BACKGROUND: Basal cell carcinoma (BCC) has been mostly associated with sun exposure, but ionizing radiation is also a known risk factor. It is not clear if the pathogenesis of BCC, namely at a genomic and epigenetic level, differs according to the underlying triggering factors. OBJECTIVE: The present study aims to compare genetic and epigenetic changes in BCCs related to ionizing radiation and chronic sun exposure. METHODS: Tumor samples from BCCs of the scalp in patients submitted to radiotherapy to treat tinea capitis in childhood and BCCs from sun-exposed areas were analysed through array comparative genomic hybridization (array-CGH) and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) to detect copy number alterations and methylation status of specific genes. RESULTS: Genomic characterization of tumor samples revealed several copy number gains and losses in all chromosomes, with the most frequent gains observed at 2p, 6p, 12p, 14q, 15q, 18q, Xp and Yp, and the most frequent losses observed at 3q, 14q, 16p, 17q, 22q, Xp, Yp and Yq. We developed a statistical model, encompassing gains in 3p and 16p and losses in 14q and 20p, with potential to discriminate BCC samples with sporadic aetiology from BCC samples that evolve after radiotherapy in childhood for the treatment of tinea capitis, which presented statistical significance (P = 0.003). Few methylated genes were detected through MS-MLPA, most frequently RARB and CD44. CONCLUSIONS: Our study represents a step forward in the understanding of the genetic mechanisms underlying the pathogenesis of BCC and suggests potential differences according to the underlying ris k factors.

Multiple Basal Cell Carcinomas of the Scalp After Radiotherapy: Genomic Study in a Case With Latency Period Over 80 Years.

ABSTRACT: Basal cell carcinoma (BCC) has been linked mostly to ultraviolet radiation exposure, but ionizing radiation has also been implicated in the genesis of a subset of BCCs occurring after radiotherapy. We present a 93-year-old woman with 4 BCCs of the scalp after radiotherapy for tinea capitis, diagnosed after a latency period of over 80 years. The largest lesion was located on the right temporal region and corresponded to a BCC of mixed type, with nodular, infiltrative, and micronodular components. We performed genomic study with array comparative genomic hybridization in samples from each BCC, which revealed more imbalances in the largest lesion than in the remaining ones, correlating with its higher histological complexity. Furthermore, this was the only lesion presenting loss at 2p22.3, where is mapped the BIRC6 gene associated with regulation of apoptosis, and loss at 16q24.3, where is mapped FANCA gene, responsible for DNA repair and maintenance of chromosome stability. Despite these differences, there were aberrations shared by all tumor samples, suggesting a common genetic signature. Our report describes, to the best of our knowledge, the longest latency period between exposure to radiotherapy and the diagnosis of BCC. The genomic study showed imbalances common to all tumor samples but also differences that could explain their heterogeneity in terms of histological subtype and biological potential. In addition, these differences could also be a consequence of different times in the evolution of the lesions at the moment of presentation, thus having a diverse combination of accumulated genomic imbalances.

Specific cutaneous infiltrates in patients with haematological neoplasms: a retrospective study with 49 patients.

BACKGROUND: Haematological neoplasms account for around 9% of all cancers, and they are recognised as an important cause of skin infiltration. However, studies analysing cutaneous metastasis of haematological neoplasms are scarce. We describe the clinical spectrum and outcomes of specific cutaneous manifestations of leukaemias, lymphomas, multiple myeloma (MM), and blastic plasmacytoid dendritic cell neoplasm (BPDN) and make a review of the literature. METHODS: Data from 49 patients diagnosed with secondary cutaneous infiltration of systemic haematological neoplasms over the last 10 years in a tertiary dermatology centre were retrospectively collected, and clinical-evolutive features were analysed. RESULTS: Most cases were lymphoma (44.9%, n = 22), followed by leukaemia cutis (38.8%, n = 19), secondary plasmacytoma (10.2%, n = 5) and BPDN (6.1%, n = 3). Nodules were the predominant type of lesion, and most patients presented with multiple (≥3) lesions. In 51% (n = 25) of cases, cutaneous infiltration was detected before the diagnosis of the underlying malignancy. The patients in diverse nosological groups did not differ in terms of survival (P = 0.052). CONCLUSIONS: We recognise the clinical heterogeneity of specific cutaneous infiltrates. The high proportion of cases in which skin involvement was key to the diagnosis of systemic malignancy emphasises the role of the dermatologist in recognising and correctly managing these patients.

Sodium-Glucose Co-transporter 2 Inhibitors in the Failing Heart: a Growing Potential.

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are a new drug class designed to treat patients with type 2 diabetes (T2D). However, cardiovascular outcome trials showed that SGLT2i also offer protection against heart failure (HF)-related events and cardiovascular mortality. These benefits appear to be independent of glycaemic control and have recently been demonstrated in the HF population with reduced ejection fraction (HFrEF), with or without T2D. This comprehensive, evidence-based review focuses on the published studies concerning HF outcomes with SGLT2i, discussing issues that may underlie the different results, along with the impact of these new drugs in clinical practice. The potential translational mechanisms behind SGLT2i cardio-renal benefits and the information that ongoing studies may add to the already existing body of evidence are also reviewed. Finally, we focus on practical management issues regarding SGLT2i use in association with other T2D and HFrEF common pharmacological therapies. Safety considerations are also highlighted. Considering the paradigm shift in T2D management, from a focus on glycaemic control to a broader approach on cardiovascular protection and event reduction, including the potential for wide SGLT2i implementation in HF patients, with or without T2D, we are facing a promising time for major changes in the global management of cardiovascular disease.

Advanced Merkel cell carcinoma-A focus on medical drug therapy.

Merkel cell carcinoma (MCC) is a rare but aggressive non-melanoma skin cancer with significant morbidity and mortality. Treatment of choice for primary and locoregional MCC is complete surgical removal with sentinel lymphonodectomy and postsurgical radiotherapy of tumor basin and locoregional lymph nodes. In nonresectable and advanced tumors, drug therapy is indicated. While cytotoxic chemotherapy has resulted in higher response rates, overall survival remained nearly unaffected. With a better insight into tumor development and biology, new treatment s became available. Immune checkpoint inhibitors result in durable responses with a better safety profile that classical combined chemotherapy. Combinations of immune checkpoint inhibitors with and without radiotherapy help to overcome acquired drug-resistance. New compounds for vaccination and oral use are on the horizon. Despite all progress, treatment of MCC remains a challenge that needs close interdisciplinary teamwork.

Primary cutaneous alveolar rhabdomyosarcoma in an adolescent - A challenging diagnosis.

Primary cutaneous alveolar rhabdomyosarcoma is an extremely rare and highly aggressive soft tissue sarcoma that predominantly arises on the extremities and perineum of adolescents and young adults. Dermatologists should be aware of these tumors in order to promptly make the diagnosis and initiate treatment.

Conradi-Hünermann-Happle syndrome: report of a novel heterozygous mutation on the emopamil-binding protein gene, c.333delC.

Conradi-Hünermann-Happle Syndrome, also called X-linked rhizomelic chondrodysplasia punctata, is a rare genodermatosis that presents with cutaneous, skeletal, and ophthalmological abnormalities. Herein, we report a full-term newborn that presented at birth with scattered blaschkolinear bands of adherent scales and scalp erosions in a spiral distribution. Genetic analysis of emopamil-binding protein gene revealed a previously undescribed heterozygous mutation of c.333delC.

Interdigital melanoma simultaneously affecting two neighboring interdigital spaces : First description in the medical literature.

BACKGROUND: Interdigital melanoma, as a subtype of acral lentiginous melanoma, is relatively uncommon in the Caucasian population. It frequently goes unrecognized for a prolonged period of time prior to diagnosis, due to its asymptomatic nature and variable clinical appearance. METHODS: We report the case of a 67-year-old Caucasian woman who presented with interdigital malignant melanoma affecting two neighboring interdigital spaces. It had evolved over a period of more than 15 years and had been initially misdiagnosed as tinea pedis due to the macerated appearance of the lesion and a positive mycologic examination. RESULTS: We highlight the striking involvement of two adjacent interdigital spaces and the neighboring area of the sole of the foot by the tumor. The melanoma was staged as IIIC, with pathologic grading T4bN2bM CONCLUSIONS: The involvement of two adjacent interdigital spaces is unusual and, to our knowledge, has not been previously highlighted in the medical literature. It may be explained, in part, by the longstanding nature of the lesion in our patient.

Erythema nodosum and sarcoid granulomas - letting the cat out of the bag.

A 41-year-old woman presented with a violaceous papule on the dorsum of the hand, large ipsilateral axillary lymphadenopathy, and tender, erythematous, subcutaneous nodules on the legs. Accompanying signs included fever, ankle swelling, and bilateral red eye. She recalled having a previous exposure to kittens one month before and had a positive family history for sarcoidosis. Histological examination of the hand lesion showed sarcoidal granulomas with positive Bartonella henselae DNA, whereas a biopsy done on the leg nodules was compatible with erythema nodosum. Cat scratch disease (CSD) typically presents as a tender regional lymphadenopathy preceded by an inoculation papule with spontaneous resolution occurring between 8-16 weeks. Cutaneous manifestations of CSD are rare, with erythema nodosum accompanying only 0.6% of cases. Although speculative, the background of a positive family history for sarcoidosis may explain the atypical presentation of this case, with red eye, persistent arthralgia, and associated sarcoidal granulomas.

'Hints' in the horn: diagnostic clues in the stratum corneum.

The stratum corneum or horny layer is the uppermost layer of the epidermis, and is mainly responsible for the skin's barrier function. In spite of its complexity at the ultrastructural and molecular level, the features accessible to visualization on conventional histology are relatively limited. Nevertheless, knowledge of subtle clues that one may observe in the stratum corneum can prove useful in a wide range of situations in dermatopathology. We herein review a selection of common and rare entities in which the horny layer may reveal significantly important hints for the diagnosis. These clues include parakeratosis and its different patterns (focal, confluent, alternating, associated with spongiosis, epidermal hyperplasia or lichenoid changes), subcorneal acantholysis, infectious organisms in the stratum corneum (including fungal, bacterial and parasitic), thickening or thinning of the stratum corneum and the presence of different kinds of pigment. Even when normal, the horny layer may prove to be useful when seen in association with severe epidermal damage, a combination of features testifying to the acute nature of the underlying pathological process.

Pyoderma gangrenosum-a novel approach?

Pyoderma gangrenosum (PG) represents a rare skin disorder, with several clinical variants and still not fully understood ethiopathogenesis. Often associated with inflammatory or neoplastic disease, PG is nowadays considered an inflammatory neutrophilic disease with common underlying morbidity. Modern treatment options are oriented towards key mechanisms underlying the pathogenesis of the disease, namely inflammatory mediators, and seem to be the most effective treatment currently available. Although promising, the results are not invariable and these treatments are sometimes surrounded by controversy, as recent studies have reported cases that are refractory to therapy with biological agents. It is possible that refractoriness to the use of biological agents as monotherapy stems from the fact that a single agent is not able to affect the entire inflammatory cascade, or to simultaneously influence all of its levels. Based on the pathogenesis of inflammation, we can suggest that an ideal targeted therapy should be able to induce the following changes: 1) reduction of the secretion of interleukin (IL)-1a/b from the inflammasome with subsequent blocking of its biological effect (by therapy with IL-1 receptor antagonists); 2) blocking of the activation of the secreted procytokines in their active form (by therapy with caspase-1 inhibitors; 3) blocking of the effect of the already released active cytokines (by therapy with tumour necrosis factor alpha, TNF-α, inhibitors); 4) blocking of the effector action of the cytokines on the target intracellular molecules (by therapy with kinase inhibitors). The specific therapy should aim to attack more than one link in the inflammatory cascade, in order to achieve maximum therapeutic effectiveness. Most surely, this could be achieved with combined therapy with different groups of biological agents (for example a combined therapy with IL-1 receptor antagonist and a TNF-α inhibitor). Currently, no data in the literature exist to support this statement, and there are no safety data relating to such approaches. We focus this review on the novel etiopathogenetic concepts of PG and the future therapeutic approaches based on blocking different levels of the inflammatory cascade, which seems to be the most promising weapon in the target-oriented treatment options.