Zdzisław Woźniak

Increased angiogenesis in cutaneous T-cell lymphomas

Primary cutaneous T-cell lymphomas (CTCL) represent a heterogeneous group of neoplasms derived from skin-homing T cells. CTCL behave similarly to indolent B-cell lymphomas. There is increasing evidence that angiogenesis may be important in lymphoproliferative disorders. The aim of the study was to evaluate microvessel density (MVD) as a parameter of tumor angiogenesis measured by the expression of CD34 in the skin samples in CTCL patients. Formaldehyde-fixed, paraffin-embedded skin tumor biopsy specimens from 25 patients (16 men, 9 women) with CTCL (mycosis fungoides), and 8 skin samples from healthy volunteers were analysed. The preparations were stained with haematoxylin and eosin, and evaluated histopathologically. Staining for endothelial cells with monoclonal antibody against CD34 revealed a mean number of 134 dots per mm2 for CTCL and 106 dots/mm2 for controls; the difference was statistically significant (p=0.0388). Our study shows a higher number of microvessels in primary CTCL compared with normal skin. Microvascular endothelial cells have become an important target in cancer therapy. Increased MVD in the skin of CTCL patients indicate that angiogenesis may play a role in the growth of CTCL, and raises the possibility of using angiogenesis inhibitors in CTCL therapy.

Expression of CXCR4 and CXCL12 and their correlations to the cell proliferation and angiogenesis in mycosis fungoides

Introduction Chemokines play an important role in tumor growth, invasion and metastasis. The CXCR4/CXCL12 axis has been implicated in development of both solid tumors and hematological malignancies and is also relevant in the pathogenesis of the most common primary cutaneous T-cell lymphoma, mycosis fungoides (MF). Aim To evaluate the expression of CXCR4 and CXCL12 in MF and to examine their associations with cell proliferation and angiogenesis. Material and methods The material for the study consisted of skin samples obtained from 56 patients with MF and 20 healthy volunteers. The expression of CXCR4 and CXCL12 was assessed by immunohistochemistry on the paraffin blocks and compared to the expression of angiogenesis marker (CD34) and proliferation indicators (Ki-67, AgNORs). Results The expression of chemokine CXCL12 and its receptor CXCR4 was significantly higher in MF than in the healthy skin (p < 0.001). There was no significant difference between early and advanced stages of MF. Similarly, there was no statistically important correlation between the expression of CXCR4/CXCL12 and angiogenesis and proliferation markers, however a significant correlation between CD34 and AgNORs expression was found (p < 0.001). Conclusions The CXCR4/CXCL12 axis seems to play an important role in MF development in the early as well as in the advanced stages of the disease. Therefore, the CXCR4/CXCL12 axis seems to be an interesting potential target for the future strategies of new drug development, giving hope for more efficacious therapies for mycosis fungoides.

Carcinoma en cuirasse as an initial manifestation of inflammatory breast cancer

Carcinoma en cuirasse is an uncommon clinical manifestation of metastatic cutaneous carcinoma characterized by diffuse sclerodermoid induration of the skin. The name was given in the first description by Velpeau in 1838 based on its resemblance to the steel breastplate of cuirassier (cavalry soldier) [1]. Other terms for this distinctive morphological variant of cutaneous metastasis include armoured cancer, Panzerkrebs, scirrhous carcinoma and Acarcine eburnee [2, 3]. Usually carcinoma en cuirasse occurs in patients with local tumour relapse after mastectomy, albeit in some subjects it develops as a presenting feature of primary breast cancer (BC) [4]. Rarely, this form of cutaneous metastasis was associated with other adenocarcinomas (e.g. carcinoma of the lung, kidney or gastrointestinal tract) [5].

Vulvovaginal‐gingival‐pilar lichen planus in a patient with autoimmune hepatitis

A 75-year-old woman with recurrent white plaques and erosions of the oral and genital mucous membranes was admitted to the hospital (Fig. 1a–c). Briefly, the patient noted that the mucosal lesions had been present for at least 7 years. The patient also complained of progressive alopecia and atrophy of the toenails. The mucosal lesions had been misdiagnosed as candidiasis, and the patient had been repeatedly treated with oral and topical antifungals, with little improvement. In addition, she had been diagnosed with autoimmune hepatitis and autoimmune thyroiditis 20 years ago and had been treated with systemic corticosteroids for many years. On admission, she was on a maintenance dose of prednisone 10 mg per day for autoimmune hepatitis. Physical examination revealed erosions on the buccal and gingival mucous membranes and white streaks on the lips, gingiva, tongue, and buccal mucosa. There were also erosions on the vagina and white plaques with atrophy on the vulva. In addition, physical examination revealed an irregular patch of cicatricial alopecia on the vertex (Fig. 1d). Trichoscopy showed loss of follicular openings, white structureless areas, and perifollicular scaling. There was also partial atrophy of the toenails. Autoimmune bullous disease was excluded on direct immunofluorescence. Histological examinations of the mucous membrane and scalp were performed and were consistent with a diagnosis of lichen planus (LP). Taking into consideration, the clinical presentation (oral and genital involvement accompanied by lichen planopilaris) and the diagnosis of vulvovaginal-gingival-pilar syndrome were made. The dose of prednisone was increased to 40 mg per day. In addition, treatment with topical clobetasol propionate for the scalp and topical tacrolimus for the mucosal lesions was started. Significant improvement was observed after 2 months of therapy, and the dose of prednisone was gradually tapered to 20 mg daily within 5 months, without a flare of the symptoms. Unfortunately, the patient was lost to further followup. Vulvovaginal-gingival (VVG) syndrome is a rare variant of LP described for the first time by Pelisse. It is characterized by the presence of a triad of symptoms, which includes vulvar, vaginal, and gingival involvement with LP. Over 200 cases have been reported so far. The syndrome might have a progressive course with significant propensity for scarring. Treatment is challenging, and a multidisciplinary approach is recommended. The first-line treatment suggested by most of the authors is the use of topical corticosteroids or tacrolimus and, when indicated, introduction of systemic prednisolone with azathioprine or mycophenolate mofetil. Early therapy with systemic immunosuppression usually needs to be combined with surgical management of the strictures and stenosis. The term “vulvovaginal-gingival-pilar (VVGP) syndrome” was coined by Olszewska et al. to highlight high percentage of the coexistence of lichen planopilaris. Taking into consideration the significant propensity for scarring in VVG-LP, the development of cicatricial alopecia should not be a surprising finding. Patients with VVG-LP are primarily treated by dentists and/or gynecologists. Therefore, the scalp lesions are frequently overlooked, and the correct diagnosis is made in advanced stages of cicatricial alopecia. Reverse cases, when mucosal involvement is

Drug-induced subacute cutaneous lupus erythematosus caused by amlodipine

Introduction. Drug-induced subacute cutaneous lupus erythematosus is a variant of lupus caused by exposure to certain drugs. It presents as annular or psoriasiform lesions located in regions which are exposed to UV radiation. Objective. To report a case of subacute cutaneous lupus erythematosus induced by amlodipine. Case report. A 78-year-old woman was admitted to our department with annular erythematous lesions which had appeared 5 months earlier on the upper extremities and trunk. Six months prior to the admission, amlodipine was added to the cardiac drugs previously used by the patient. The clinical findings and results of additional diagnostic tests suggested the diagnosis of drug-induced subacute cutaneous lupus erythematosus. Amlodipine was discontinued and adjuvant treatment was introduced, resulting in a significant improvement in skin condition. Conclusions. In cases of subacute cutaneous lupus erythematosus, particularly those developing in patients aged 50 and older drugs, including amlodipine should always be considered as possible causative factors. A detailed analysis of medications used by such patients is necessary to determine the potential of the drugs to induce lesions and the time frame during which such lesions typically arise.

Multiple disseminated keratoacanthoma-like nodules: a rare form of distant metastases to the skin

Cutaneous metastases are found in approximately 0.7–10.4% of internal malignancies and they may rarely be the first symptom of the underlying neoplasm [1]. Typically, cutaneous secondaries present as a single, erythematous nodule, occasionally ulcerated, however, other presentations, including erysipelas carcinomatosa, alopecia neoplastica or carcinoma en cuirasse in the course of the breast cancer, or angiomatous tumors in the course of renal carcinoma may be occasionally observed. The metastases assimilating keratoacanthomas are extremely rare [2, 3]. Herein, we present a 72-year-old man, cigarette smoker, who was referred to our department with disseminated skin tumors of unknown etiology. On admission, domeshaped, inflamed tumors, some of them with central, keratin-filled craters, clinically mimicking keratoacanthomas were observed on the scalp, forehead, nose, neck and trunk (back and left shoulder) (Figures 1, 2). All the

Hirudotherapy – a rare cause of pseudolymphoma

225 Cutaneous pseudolymphoma (C-PSL) represents a heterogeneous group of cutaneous reactions characterized by polyclonal T and/or B cell proliferation [1, 2]. The disease can be either idiopathic or triggered by various stimuli including infections, primarily Borrelia burgdorferi and drugs [3, 4]. Several lines of evidence indicate minor traumas such as tattoos, acupuncture, insect bites and vaccination as C-PSL inducers [3, 4]. Herein, we present a rare case of a C-PSL provoked by hirudotherapy. A 38-year-old woman was admitted to the Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, for diagnosis and treatment of skin lesions that appeared 7 months before hospitalization. On admission, physical examination revealed 10 well-defined, firm and pruritic nodules, red in color, ranging from 6 to 10 mm in diameter in her pubic area (Figures 1 A, B). The skin changes appeared soon after the patient underwent hirudotherapy that had been recommended by her friend as a successful treatment for uterine myoma. The pruritic cutaneous lesions appeared after the first procedure, however the patient decided to apply the second therapy after 3 weeks. Each time 5 leeches were used. For the apparent skin lesions the patient was given oral antihistamines and moderate potent topical glucocorticosteroids with no improvement. The patient did not take any other medicines, except for ulipristal acetate 5 mg/day, orally, administered by a gynecologist for the uterine myoma. Laboratory tests (morphology, urinalysis, lipids, liver function, renal function and inflammation markers) were within normal ranges. Histological examination of the skin biopsy revealed irregular acanthosis and mixedcell infiltration, composed of lymphocytes, histiocytes, plasma cells and eosinophils in the dermis. An evident exocytosis with focal spongiosis and intraepidermal inflammatory infiltration were observed. In the immunohistochemical study, the lymphocyte population consisted of a mixed population of T and B lymphocytes with T cell predomination. The T lymphoid cells were positive for CD3, CD43, CD45RO, CD4, CD8, CD30, CD20, CD79a, CD138. The numerous epithelioid histiocytes were CD68 positive. The proliferative rate measured by Ki-67 expression was low (labeling index = 7%). Based on the histological, immunohistochemical results and clinical observations the diagnosis of C-PSL was made. Initially, the skin changes were treated with 100 mg hydrocortisone intralesionally and topical glucocorticosteroid ointment (clobetasol propionate) applied twice a day. Cryotherapy was used in the case of one nodule, however the results were unsatisfactory as the nodule became discolored. After 4 weeks of topical treatment, nodules became smaller and less red but remained firm. We modified the previous therapy by adding methylprednisolone acetate intramuscularly 40 mg every 4 weeks. We chose intramuscular instead of intralesional drug administration because the patient had a bad experience with previous mesotherapies and preferred systemic treatment (one injection) instead of a series of injections. The patient continued treatment for 20 weeks with a slow regression of skin lesions. Cutaneous pseudolymphomas are not a rare dermatological problem, however, due to the overlapping histopathological and clinical features they may create a diagnostic and therapeutic challenge even for experienced dermatologists [5, 6]. To diagnose C-PSL, histological and clinical criteria must be fulfilled [5, 6]. Clinical criteria include typical location and morphology of the skin changes as well as characteristic clinical course of the disease. Typically, skin changes appear on the face, which is the most common localization of the lesions, on the chest and upper extremities. They are usually single and localized nodules or plaques, red to purple in color and tend to be self-regressing or disappear when the causative factor is removed [3]. Histological features of C-PSL include polyclonal lymphocyte infiltration in the upper layers of the skin. According to the predominant Letter to the Editor

Diffuse melanosis cutis related to dermal micrometastases as the first clinical symptom of distant metastatic malignant melanoma: Case report

Rationale: Diffuse melanosis cutis (DMC) is a very rare sign of malignant melanoma progression. The condition usually develops after approximately one year from melanoma diagnosis in a patient with metastatic tumors and after anticancer treatment with cytostatic medications. Patient concerns: A 72-year old Caucasian man was admitted to the Department of Dermatology with DMC for 4 months and the history of two melanomas treated surgically 30 years and 9 months before present hospitalization. Diagnosis: Histological and immunohistochemical examinations of DMC biopsy indicated melanoma metastatic cells as well as free deposits of melanin and melanophage presence in the dermis. Interventions: The patient refused to the treatment. Outcomes: The patient died eight months after DMC appeared. Lessons: DMC is a rare presentation of advanced MM and is a bad prognostic factor. The pathomechanisms of the discoloration of the skin are not fully explained. The role of micrometastases, as well as melanin precursors, released during lysis of MM metastases, and growth factors may play a role in the development of the symptom.

The new indexes comparing the radicality of tumor removal and the extent of post-operative defects after treatment of basal cell cancer by mean of Mohs Surgery and Classical Excision

Mohs Surgery (MMS) and Excision with Predetermined Margins (EPM) vary in form and width of tumor removal. Exact measurements and calculations of the related values enable to compare precisely those methods. Materials and methods: In 668 BCC cases treated with MMS, the following measurements and calculations were carried out: a) the widest margin of excision [Marg max MMS], b) the mean margin of excision [Marg mean MMS], c) the hypothetical margin of excision in EPM [Marg EPM]. The two comparative indexes were proposed: d) index of radicality of tumor removal [IRTR] calculated by dividing [Marg max MMS], and [Marg EPM], and e) index of extensions of the defects [IED] calculated by dividing the [Marg mean MMS] and [Marg EPM]. Results: a) [Marg max MMS] ranged from 1 mm to 40 mm, b) [Marg mean MMS] 1 to 24.1 mm, c) [Marg EPM] 1 mm to 15 mm, d) [IRTR] ranged 33,3% to 444% (on average 106.20%), e) [IED] 33,3% to 344.41% (on average 84.93%). Conclusions: The excision of BCC with MMS was performed more radically (by mean of 6.2% not singificant statistically), the extent of defects was smaller (by mean of 15.07% -statistically significanct) compared to EPM. Correspondence to: Andrzej Bieniek, Department of Dermatology, Venereology and Allergology at Wroclaw Medical University, Poland, E-mail: abieniek@cmbieniek.pl

Blastic plasmacytoid dendritic cell neoplasm: a rare lymphoma of extremely aggressive course

Blastic plasmacytoid dendritic cell neoplasm (BPDCN), formerly known as blastic NK cell lymphoma or CD4+/CD56+ hematodermic neoplasm, is a rare aggressive disorder of a not fully understood etiology [1]. It predominantly involves the skin and has a high risk of leukemic dissemination [2]. The disease has an aggressive course and poor long-term prognosis with a median survival of 12–16 months [3]. We report a patient, who displayed clinical and immunohistochemical features of BPDCN with no primary bone marrow involvement. The disease had an extremely rapid course, which led to the patient’s death in 4 months after the first lesions had developed. A 70-year-old Caucasian male was referred to our Department in December 2014 with a 2-month history of rapidly developing asymptomatic nodules and plaques on the head, neck and upper part of the trunk. On physical examination, we saw disseminated red-to-purple indurated nodules and bruise-like plaques located predominantly within the head, neck and upper part of the trunk (Figure 1). The biggest plaques, located on the right cheek, chin and back were round, well-circumscribed, red-to-purple, had up to 7 cm in diameter and presented discrete scaling on the surface. Numerous smaller red and brownish indurated lesions were located within the face, back and chest. There were no signs of peripheral