Synchronous occurrence of primary cutaneous B-cell lymphoma and cutaneous Rosai-Dorfman disease in distinct lesions: A unique association.

Rosai-Dorfman disease, also known as sinus histiocytosis with massive lymphadenopathy (SHML), is a rare subtype of reactive histiocytosis which is seldom associated with Hodgkin's and non-Hodgkin's lymphomas. To date, the coexistence in the same patient of extra nodal SHML and primary cutaneous B-cell lymphoma (PCBCL) has been reported in the literature, as metachronous diagnosis in the anatomical area of the original PCBCL or synchronous occurrence in the same lesions. However, no data have been published as for synchronous occurrence of the two pathological entities in distinct anatomical sites. Herein, we report the first ever described synchronous occurrence of PCBCL and SHML, detected in distinct lesions, affecting the same patient. The complete resolution of the patient's PCBCL after rituximab treatment and the concomitant regression of SHML suggest that this clinically benign reactive histiocytic proliferation, potentially triggered by the lymphoma microenvironment itself, may take place not only in the site of the PCBCL lesion, but also in other distant areas not directly affected by the primary cutaneous lymphoma.

Oncoviruses and melanomas: A retrospective study and literature review.

The role of human oncoviruses in melanoma has been poorly investigated. The aim of this study was to investigate the association between oncoviruses and melanomas searching for human papillomavirus (HPV), Epstein Barr virus (EBV), and human herpesvirus 8DNA in melanoma specimens. Formalin-fixed and paraffin-embedded tissue specimens of cutaneous, mucosal, and ocular melanomas (OM) were selected from the Pathology Departments of the Galliera Hospital (Genoa) and the University Hospitals of Turin and Cagliari. Cutaneous and mucosal nevi have been collected as controls. The oncoviruses search has been performed with different polymerase chain reaction reagent kits. Fifty-four melanomas (25 mucosal, 12 ocular, and 17 cutaneous) and 26 nevi (15 cutaneous and 11 mucosal) specimens were selected. The detection rate for one of the investigated oncoviruses was 17% in mucosal, 20% in ocular, and 0% in cutaneous melanomas (CMs). Despite the differences between groups seeming remarkable, there was no statistical significance (p > 0.5). Our data do not support a primary role of oncoviruses in melanoma carcinogenesis; however, the finding of HPV and EBV DNA in a considerable fraction of mucosal and OMs suggests that these viruses may act as cofactors in the development of extra-CMs.

A monolateral pigmented lesion of the nipple.

Pigmented mammary Paget's disease is a very rare variant of mammary Paget's disease linked to an underlying carcinoma in almost all cases. We present the case of a 62-year-old female patient who came to our attention for the evaluation of a monolateral asymptomatic pigmented lesion of the right nipple, which turned out to be a pigmented mammary Paget's disease unassociated to an underlying malignancy - an extremely rare entity only anecdotally reported in literature. The two main peculiarities of our patient's lesion, the importance of immunohistochemistry in the differential diagnosis and the theories on its pathogenesis are discussed. Further studies are necessary to establish the best treatment options. Click here for the corresponding questions to this CME article.

The clinical spectrum of COVID-19-associated cutaneous manifestations: An Italian multicenter study of 200 adult patients.

BACKGROUND: COVID-19 is associated with a wide range of skin manifestations. OBJECTIVE: To describe the clinical characteristics of COVID-19-associated skin manifestations and explore the relationships among the 6 main cutaneous phenotypes and systemic findings. METHODS: Twenty-one Italian Dermatology Units were asked to collect the demographic, clinical, and histopathologic data of 200 patients with COVID-19-associated skin manifestations. The severity of COVID-19 was classified as asymptomatic, mild, moderate, or severe. RESULTS: A chilblain-like acral pattern was significantly associated with a younger age (P < .0001) and, after adjusting for age, significantly associated with less severe COVID-19 (P = .0009). However, the median duration of chilblain-like lesions was significantly longer than that of the other cutaneous manifestations taken together (P < .0001). Patients with moderate/severe COVID-19 were more represented than those with asymptomatic/mild COVID-19 among the patients with cutaneous manifestations other than chilblain-like lesions, but only the confluent erythematous/maculo-papular/morbilliform phenotype was significantly associated with more severe COVID-19 (P = .015), and this significance disappeared after adjustment for age. LIMITATIONS: Laboratory confirmation of COVID-19 was not possible in all cases. CONCLUSIONS: After adjustment for age, there was no clear-cut spectrum of COVID-19 severity in patients with COVID-19-related skin manifestations, although chilblain-like acral lesions were more frequent in younger patients with asymptomatic/pauci-symptomatic COVID-19.

Spiky/keratosis-pilaris-like early follicular mycosis fungoides: A clinicopathologic study of 20 cases with extended follow-up.

BACKGROUNDS: Follicular mycosis fungoides (FMFs) is a distinct form of T-cell lymphoma whose course is considered aggressive. METHODS: A retrospective study with long-term follow-up of 20 patients diagnosed with spiky/keratosis-pilaris-like FMF between 2008 and 2017 was conducted. RESULTS: Twelve males and eight females were identified, with a mean age at first diagnosis of 59 years (range 42-86). Hyperkeratotic follicular papules were the sole clinical finding in 16 of 20 patients. A diagnostic delay between first symptom development and initial diagnosis was frequent (mean 42 months). The head/neck region was concurrently affected only in two patients. Disease stage at diagnosis was IA in two patients (10%) and IB in 18 (90%). Five patients had almost complete lesion regression, whilst there was only a slight improvement, without regression in 14. Two patients developed infiltrated papules, comedones, and small cysts during follow-up. Only one patient progressed to tumor stage (IIB) five years after the first diagnosis. The mean follow-up was seven years (range: 12-180 months). None of them died of cutaneous lymphoma. CONCLUSIONS: FMF presenting with only spiky/keratosis-pilaris-like lesions have an excellent prognosis at medium-term follow-up. Early recognition of patients with this peculiar FMF presentation might lead to identifying prognostic factors.

Cytotoxic-mediated spontaneous regression of inflammatory cutaneous metastases of breast carcinoma.

Spontaneous regression (SR) of cancer is a rare but well-documented biological phenomenon, which is even rarer in the context of metastatic breast carcinoma. Different mechanisms of SR are still under debate, including immune-mediated response. We herein report a case of the SR of intralymphatic cutaneous metastases of a breast carcinoma with spontaneously-induced T-cell-mediated cytotoxic response. An 86-year-old female was diagnosed with locally advanced right breast carcinoma and axillary lymph node metastases, without distant metastases The patient refused any therapy. Six months afterwards, she developed multiple, asymptomatic purpura-like plaques with prominent teleangectasias on her right chest wall, continuous to the previous surgical scar and on her ipsilateral abdomen. Skin biopsy showed aggregates of atypical cells admixed with erythrocyte thrombi within dilated dermal lymphatic vessels. SR of the cutaneous lesions occurred within 6 months and persisted at the 15 months follow-up in the absence of therapy, whilst no signs of internal relapse were observed. Immunohistochemically, the estrogen-negative, CK7-positive, C-erb B2-positive intralymphatic metastases were associated with extensive infiltration of CD8-positive cytototoxic T lymphocytes. Factors that may have precluded the implantation of intralymphatic metastases leading to SR are discussed, with local immune surveillance being one major hypothesis.

Emergency accesses in Dermatology Department during the Covid-19 pandemic in a referral third level center in the north of Italy.

During the lockdown period, most planned visits have been postponed and the number of accesses to emergency department (ED) has dramatically reduced. The aim of our study is to analyze the impact of the lockdown on the number, type, and severity of Dermatological ED diagnosis. We performed a retrospective review of all dermatological consultations in the ED of IRCSS San Matteo during the lockdown period in Italy (February 22-May 3 2020) and compared them with those from the same period in 2019. We noticed a sharply reduction in the number of dermatological consultations requested in the ED: from 164 patients in 2019 to 33 in 2020. Some diagnostic categories showed a significant difference with a higher incidence of vasculopathic lesions (0.6% vs 12.1%, P < .0001), urticarial rashes (8.5% vs 21.2%, P = .03), and scabies (3% vs 12.1%, P = .023). We observed an increase in the proportion of patients starting medications, before coming to the ED 26.2% in 2019 vs 66.7% in 2020 (P < .001). Furthermore, we noticed a significant increase in the average complexity of cases presenting to the ED in 2020, as proven by the increased need for biopsies and systemic therapy.

Does therapy with biological drugs influence COVID-19 infection? Observational monocentric prevalence study on the clinical and epidemiological data of psoriatic patients treated with biological drugs or with topical drugs alone.

Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, there has been an open debate on the impact of biological drugs used in the treatment of psoriasis. To define whether patients under treatment with biologics suffer from increased morbidity and mortality from COVID-19, compared to psoriatic patients treated only with topical drugs, we designed an observational monocentric prevalence study recording the personal and clinical data of psoriatic patients, with focus on the presentation of signs and symptoms related to COVID-19 in the period of time ranging from 1 January 2020 to 31 May 2020. A total of 180 patients were enrolled into two groups: 100 patients in the topical therapy group and 80 patients in the biological therapy group. No statistically significant difference was found between the groups regarding the prevalence of COVID-19 infection and symptoms at a bivariable analysis with adjustment for confounders. In conclusion, psoriatic patients under treatment with biologics do not seem to be more susceptible to COVID-19 compared to other psoriatic patients and we suggest not interrupting treatment with biological drugs, even in areas suffering from active outbreaks of the disease.

Erosive pustular dermatosis of the scalp: A neutrophilic folliculitis within the spectrum of neutrophilic dermatoses: A clinicopathologic study of 30 cases.

BACKGROUND: It is general opinion that histopathology is nonspecific and of little value in diagnosing erosive pustular dermatosis of the scalp (EPDS). OBJECTIVES: Clinicopathologic correlation of erosive pustular dermatosis of the scalp. METHODS: We reviewed the clinical and pathologic records of patients with a clinicopathologic diagnosis of EPDS between 2011 and 2016 at the Dermatopathology Unit of Turin University. RESULTS: Thirty elderly patients with EPDS were identified (22 men and 8 women). Androgenetic alopecia was present in 19 of 30 patients. Triggering factors included mechanical trauma in 10 of 30 cases, surgical procedures in 4 of 30 cases, and herpes zoster in 1 of 30 cases. Three patients were affected by autoimmune disorders. The vertex was the most common location. Disease presentation varied markedly from tiny, erosive, scaly lesions to crusted and hemorrhagic plaques, mimicking pustular pyoderma gangrenosum. The pathologic changes differed according to lesion type and disease duration. Interestingly, a spongiotic and suppurative infundibulo-folliculitis was observed in 8 of 30 cases. LIMITATIONS: This was a retrospective study. CONCLUSIONS: We believe that the primary lesion of erosive pustular dermatosis of the scalp is a spongiotic, pustular superficial folliculitis. The clinicopathologic similarities with other neutrophilic dermatoses, such as pustular pyoderma gangrenosum, suggest this condition should be included in this spectrum, where pathergy plays a pathogenetic role.

Eruptive ulcerative follicular spicules heralding progression of smoldering multiple myeloma.

Herein, we describe a patient with immunoglobulin G (IgG)-lambda smoldering multiple myeloma with translocation t(4:14) who developed widespread ulcerative horny-like spicules, heralding rapid progression to overt myeloma requiring aggressive chemotherapy and autologous stem cell transplantation. The serum abnormal immunoglobulin in the blood was cryoglobulin, which typically precipitates in the tissues at low temperatures causing inflammation and tissue damage. Histopathological changes, observed in lesions at different evolutionary stages, evidenced columns of horny-like eosinophilic homogeneous material, immunoreactive for IgG lambda, protruding from the dilated and/or distorted follicular openings or acrosyringia and small vessel thrombotic vasculopathy and vasculitis in concert with an inflammatory neutrophilic and lymphocytic reaction. Biochemical investigations on material from a spicule and ulcero-necrotic lesion revealed cryoprecipitates containing IgG-lambda with electrophoretic characteristics identical to those of the serum dysprotein. Our findings suggest that the formation of spicules and development of ulcerative lesions are a part of the same clinical spectrum where the cold-dependent precipitation of the immunogenic dysprotein, both in the skin vessels and hair follicle infundibula, play a major pathogenetic role. Whether this highly characteristic paraneoplastic dermatosis can identify patients with high-risk cytogenetic abnormalities and be incorporated into prognostic models, applicable early on in the course of myeloma, warrants further investigation.

Photo-photochemotherapy in Juvenile-onset Mycosis Fungoides: A Retrospective Study on 9 Patients.

Mycosis fungoides (MF) is a rare disease and is considered the most common form of cutaneous T-cell lymphoma. Given the infrequent incidence of MF in patients under the age of 20, there are no established guidelines for the treatment of these patients; the overwhelming majority have an early-stage disease and progression to more advanced stages is very rare. This study presents the safety and effectiveness of photo-photochemotherapy as a first-line approach in the treatment of an early-stage MF even in young patients.

Chronic amastigote-negative cutaneous leishmaniasis: A clinical, histopathologic and molecular study of 27 cases with emphasis on atypical and pseudolymphomatous presentations.

BACKGROUND: Chronic amastigote-negative cutaneous leishmaniasis (CL) is a diagnostic challenge, as the parasite load may be low, or absent in biopsy tissue sections. METHODS: A series of consecutive biopsy specimens, taken from 130 patients with a diagnosis of granulomatous dermatitis of unknown etiology, were reviewed. Polymerase chain reaction (PCR) was carried out for Leishmania-specific DNA. RESULTS: A total of 27 of 130 samples were positive for Leishmania-specific DNA. In only 3 patients was a clinical diagnosis CL made. The lesions were, single or multiple nodules or plaques of many months duration. Histopathologically, a tuberculoid granulomatous dermatitis was the least common denominator in every case, whilst in 5 cases a heavy lymphoid component was predominant. One patient had a concurrent cutaneous marginal zone lymphoma (MZL), the additional PCR study showed the presence of Leishmania DNA in tissue. CONCLUSIONS: The results of this study expand on previous observations as to the deceptive clinicopathologic manifestations of chronic CL, confirming the diagnostic value of PCR analysis for Leishmania DNA in unspecified granulomatous dermatitides. We also suggest that, in countries where Leishmaniasis is endemic, PCR for Leishmania-specific DNA be performed in any idiopathic pseudolymphomatous. More compelling evidence as to whether chronic Leishmania infection is implicated in the pathogenesis of some cutaneous MZL is warranted by further studies.

Erythema multiforme-like lesions in primary cutaneous aggressive cytotoxic epidermotropic CD8+ T-cell lymphoma: A diagnostic and therapeutic challenge.

Primary cutaneous aggressive cytotoxic epidermotropic CD8+ T-cell lymphoma is an extremely rare, rapidly progressing, cutaneous lymphoma, with frequent systemic involvement and poor prognosis, that still represents a diagnostic and therapeutic challenge, especially in the early stage. Herein, we report a case of an elderly woman with a fulminant course, who at onset presented with clinical and pathological features mimicking erythema multiforme (EM) and treated with cyclosporine that led to rapid deterioration with fatal outcome 6 months after disease onset. Histopathology showed a lichenoid, epidermotropic and nodular, angiocentric, dermal and subcutaneous infiltrate of sF1, CD8+, CD45RA+ small to medium-sized atypical lymphoid cells, which strongly expressed cytotoxic markers. Monoclonal T-cell-γ receptor was clonally rearranged and array-CGH showed numerous chromosomal imbalances. This case evidences the clinical, pathological and therapeutic challenges involved in this tumor. The first biopsy showed an interface dermatitis-like pattern, revealing the deceptive features that early cutaneous infiltrates of this aggressive lymphoma may have. A high suspicion for aggressive CTCL and a low threshold for repeat biopsies should be maintained when faced with rapidly progressing and/or ulcerative EM-like lesions, especially if immunomodulatory therapy is being considered.

'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.

Cordoniform morphea: a clinicopathologic study of two cases presenting with the rope sign.

BACKGROUND: Morphea clinically presenting as cordoniform lesions has not been described previously in the literature. OBJECTIVE: Our goal was to describe the clinicopathologic features of morphea presenting with cord-like cutaneous lesions. METHODS: The clinical notes of 420 patients with a diagnosis of morphea seen during the previous 10 years were reviewed to identify any cases that had cordoniform lesions at presentation. RESULTS: Two adult patients (one male and one female) were identified. Both patients presented with chronic, slightly burning, bilateral, erythematous, linear or curvilinear elevated cutaneous indurations on the lateral chest wall strikingly reminiscent interstitial granulomatous dermatitis with arthritis. Histopathologically, typical changes of deep morphea with a band-like involvement only of the lower part of the reticular dermis and the superficial hypodermis and a remarkable perineural arrangement of the lymphoplasmocytic infiltrate were observed. The presence of Borrelia in skin biopsy samples of both patients was shown by immunohistochemistry and focus floating microscopy. In one patient, the presence of Borrelia afzelii DNA in the cutaneous biopsy was shown by polymerase chain reaction. CONCLUSIONS: Cordoniform morphea is an exceedingly unusual and previously undescribed clinicopathologic presentation of morphea where Borrelia infection may play a causal role.

Squamocellular Carcinoma of the Skin: Clinicopathological Features Predicting the Involvement of the Surgical Margins and Review of the Literature.

BACKGROUND: The new AJCC classification has highlighted some particular risk factors for squamous cell carcinoma (SCC) relevant for prognosis. Incomplete excision is not infrequent in SCC. The aim of this study is to examine features that can predict an incomplete excision on the basis of the new AJCC classification and to review the literature on this topic. MATERIALS AND METHODS: 81 SCC patients were included. All patients were submitted to excisional biopsy with a margin of at least 4 mm from the clinical edges as recommended. Histological characteristics of the lesions analysed were maximum diameter, grading, site, Breslow thickness, Clark level, deep tissue invasion (neural, bone, muscle), presence of ulceration and positivity of the margins. RESULTS: The average Breslow thickness was 3.93 mm. Out of the 81 patients included, 14 showed involved margins. The 2 parameters that were implicated in predicting involvement of the margins in the multivariable model were Breslow thickness and location of the lesion on the ear or lip. Grading was not associated with involvement of margins. CONCLUSION: According to the new AJCC classification, this study could be useful to plan the most suitable surgical technique in order to avoid the risk of incomplete surgery.