Beate Weidenthaler-Barth

Early diagnosis of intravascular large B‐cell lymphoma

In 1959, Pfleger and Tappeiner described a disorder they referred to as “systematized endotheliomatosis of the cutaneous blood vessels” [1]. Despite extensive histomorphological studies, at the time the authors were unable to differentiate whether the lesion represented an unusual carcinoma or hemangioendothelioma. Only many years later was this disorder characterized as intravascular large B-cell lymphoma (IVLBCL) [2]. Since the last decade of the 20th century, the WHO lymphoma classification has listed IVLBCL as subtype of diffuse large B-cell lymphoma (DLBCL) [3]. Herein, we present a case of this very rare disease. In May 2014, the 76-year old female patient first presented to our clinic with a one-year history of erythematous lesions on her legs, which at times gave rise to a burning sensation. She denied recurrent episodes of fever, night sweats, and weight loss. Clinical examination revealed – occasionally bizarrely shaped – livid patches on both legs (Figure 1). Histology showed large atypical cells with pleomorphic nuclei located inside dilated vessel lumina throughout the entire dermis as well as parts of the subcutis. Some of the affected vessels were thrombosed (Figure 2a, b). Immunohistochemically, the cell aggregates showed reactivity for CD20, CD79a, and MUM-1; partially, also for bcl2. The proliferation rate – using MiB1/Ki67 – was increased. The neoplastic cells did not label with CD3, CD10, bcl6, and pancytokeratin MNF116. The endothelial markers CD31 and CD34 showed regular staining of blood vessels, and thus emphasized the intravascular location of tumor cells (Figure 3a, b). While extravascular macrophages/histiocytes and some intravascular monocytes were positive for CD68, intravascular tumor cells showed no such reaction. Immunohistochemistry also showed kappa light-chain restriction (in the absence of lambda reactivity). Molecular analysis showed B-cell clonality (B-cell clonality analysis using multiplex PCR). There was no evidence of tumor cells in the cerebrospinal fluid. Histological examination of osseous tissue (bone punch biopsy) showed regular trilinear hematopoiesis without infiltration of pathological cells. Borrelia serology was negative. Imaging studies (cranial MRl, and CT of the neck, thorax, and abdomen) revealed no evidence of extracutaneous disease involvement; the only remarkable findings included hepatic and ovarian cysts as well as cholelithiasis. The liver was slightly enlarged. Lab tests showed elevated levels of total bilirubin (1.51 mg/dL, normal range Figure 1 Bizarrely shaped livid patches on both legs.

Pembrolizumab-induced lichen planus pemphigoides in a patient with metastatic melanoma

Immune checkpoint inhibitors targeting PD-1 (programmed cell death receptor 1) are indicated in the treatment of advanced melanoma. Cutaneous complications represent the most common immune-related adverse events (irAEs) [ 1 ] . We present the case of an advanced melanoma patient with complete response to treatment with the anti-PD-1 antibody pembrolizumab who developed lichen planus pemphigoides (LPP). A 64-year-old Caucasian man with metastatic melanoma was enrolled in the MK-3475-002 phase II trial comparing pembrolizumab 2 mg/kg or 10 mg/kg (randomized and blinded for the dose received) with standard chemotherapy. Tumor staging showed a partial response after nine cycles of pembrolizumab (given at three-week intervals). However, a CTCAE (Common Terminology Criteria for Adverse Events) grade 2 bullous pemphigoid (BP)-like drug reaction with vesicular lesions of the oral mucosa (Figure 1 a) and scattered papules with central vesicles on the skin prompted the patients exclusion from the trial. Subsequent treatment with topical clobetasol, prednisolone (1 mg/kg PO, followed by a slow taper over the course of four months), and rituximab (375 mg/m2 IV every four weeks; discontinuation after three doses due to CTCAE grade 3 thrombocytopenia) only led to minor improvement of the skin lesions. Six months later, the patient presented with a complete tumor response but also with CTCAE grade 3 white reticular lesions of the oral mucosa ( Wickham striae , Figure 1 b) and pruritic erythematous papules and plaques with central vesicles on the trunk and extremities (Figure 1 c). Histology (biopsy taken from the back) was consistent with lichen planus (LP), showing orthohyperkeratosis, hypergranulosis, cytoid bodies, and lichenoid interface dermatitis with a band-like lymphocytic infi ltrate obscuring the dermoepidermal junction (Figure 1 d, e). Repeated treatment with topical clobetasol and prolonged therapeutic attempts with systemic prednisolone (1 mg/kg PO, followed by a gradual taper over the course of eight months), PUVA therapy (methoxsalen 60 mg PO and UVA 1,2 J/cm2 four times weekly for three weeks), acitretin (50 mg PO once a day for one week), and sirolimus (2 mg PO once a day, discontinuation after eight weeks due to CTCAE grade 3 heart failure) were unsatisfactory.

Blistering of the hands following a manicure at a nail salon

A 29-year-old patient attended our outpatient clinic for the fi rst time. She reported that she had had a manicure at a nail salon seven months earlier. During this procedure, various topical agents had been applied to the nails of both hands, which had then been placed under a UV lamp (for acrylate polymerization). After the treatment, blisters had formed on the dorsal of the fi ngers and hands bilaterally. The skin on the palmar aspects of the fi ngers and hands had been normal. Given the suspected diagnosis of hand dermatitis, PUVA therapy had been initiated by an offi ce-based dermatologist without further diagnostic workup. Subsequently, this had led to further clinical deterioration. The patient had no past medical history. Apart from a contraceptive containing estrogen, she was not taking any medication. She admitted to regularly consuming alcohol (1–2 glasses of wine per day).

Acquired symmetric asymptomatic lesions at the inner corners of the eyes

We report on a 35-year-old male patient who presented to our outpatient department with progressive skin lesions at the inner corners of the eyes. Symptoms had existed for two years; pruritus or pain were denied. His past medical history was unremarkable except for allergic rhinoconjunctivitis and myopia. The patient reported that he had started wearing a new pair of glasses some time before. At some point thereafter, the aforementioned skin lesions had occurred. Switching to contact lenses had not led to any clinical improvement.

Frühzeitige Diagnose des intravaskulären großzelligen B‐Zell‐Lymphoms

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