SQUIZ your knowledge! Disseminated violaceous patches, plaques, and nodules in an elderly patient.

Tre-P-29 - Vindesine dexamethasone as a therapeutic option in elderly blastic plasmacytoid dendritic cell neoplasms: a monocentric experience

A case of relapsed systemic multiple myeloma mimicking adenopathy and extensive skin patch overlying a plasmacytoma

Sweet's Syndrome: Systemic Signs and Symptoms and Associated Disorders

A 55‐year‐old man presented with recurrent multiple ulcerative nodules and plaques of 1‐year duration over the lower extremities. They were recalcitrant to topical (hydrocortisone cream) and systemic (pentoxyfylline, cefotiam) drugs. Skin surface examination of the affected areas showed the skin to be studded with violaceous nodules and/or plaques. A few of these had draining ulcers. The nature of the fluid was serosanguous. The lesions were located on the shins of the legs (Fig. 1). They were bilateral and asymmetrical. In addition, nontender, erythematous nodules of annular configuration were located on the right knee and elbow, and a few toes. The arterial pulsation was within normal limits. Serial hematoxylin‐eosin stained sections prepared from a representative lesion were marked by the presence of palisading granulomatous dermatitis (Fig. 2). A granulomatous folluculitis in the deep dermis and a thrombotic arteriole in the subcutis were also found. Sections counter‐stained for the presence of acid‐fast bacilli were negative. Paraffin‐embedded biopsy specimens were subjected to DNA analysis using the IS6110 gene as a polymerase chain reaction (PCR) primer, and were found to be positive. Serial chest X‐rays taken at an interval of 4 months showed findings indicative of active pulmonary tuberculosis. Anti‐tubercular therapy (ATT) comprising 450 mg of rifampicin, 300 mg of isoniazid, 800 mg of pyrazinamide and 1500 mg of ethambutol was administered for a period of 2 months followed by 450 mg of rifampicin and 300 mg of isoniazid for another 2 months. There was perceptible healing of the lesions, leaving atrophic and hyperpigmented scars.Multiple, violaceous, ulcerated plaques and nodules on the shins of both legsimagePalisading granuloma (H&E, × 50)image

Castleman's disease (CD) is a rare low-grade B-cell lymphoproliferative disorder that can be associated with a variety of antibody-mediated paraneoplastic syndromes. The disease is classified clinically by two forms and three histologic variants. We describe the clinical and pathological features of a 44-year-old woman who presented with an autoimmune hemolytic anemia, thrombocytosis, polyclonal gammopathy, axillary lymphadenopathy, hepatosplenomegaly, and several erythematous and violaceous nodules and plaques without scaling involving the trunk and extremities. Histologic examination of the skin lesions revealed a deep dermal and subcutaneous nodular mononuclear infiltrate composed primarily of polyclonal plasmacytoid cells without atypia and an increased vascular proliferation. Additional studies including a bone marrow and lymph node biopsy, serum and urine protein electrophoresis, and computed tomography scans supported the diagnosis of multicentric plasma cell variant of CD with an associated autoimmune paraneoplastic hemolytic anemia. Cutaneous involvement in CD is part of the multicentric nature and should be considered in the differential diagnosis of a polyclonal plasma cell-rich lymphoproliferative disorder associated with paraneoplastic autoimmune disease.

Specific cutaneous involvement in patients with multiple myeloma (MM) is very uncommon. It usually occurs in late stages of MM as a reflection of increased tumor cell burden. We studied 8 patients with cutaneous involvement of MM without underlying bony lesions and reviewed the literature on this rare dermatologic manifestation. We were particularly interested in the clinical course of patients with MM and cutaneous metastases, including survival once metastases were detected and the possible influence of various forms of therapy. Our goal was also to identify the immunoglobulin and the light-chain type in these cases, with emphasis on any possible association between a particular immunoglobulin class and cutaneous involvement, as well as the histopathologic, immunohistochemical, and cytogenetic features of the neoplastic plasma cells involving the skin. University department of dermatology, university hospital, and private practice. Medical records and biopsy specimens from 8 patients with MM and specific cutaneous lesions were reviewed. Cutaneous lesions consisted of multiple erythematous or violaceous nodules or plaques with a wide anatomical distribution. Histopathologically, 2 different patterns were identified: nodular and diffuse interstitial. Neoplastic plasma cells showed atypical features, and in 1 case they displayed a spindle shape, giving a sarcomatoid appearance to the lesion. Immunohistochemical studies demonstrated that neoplastic plasma cells were strongly positive for CD79a, CD138, and epithelial membrane antigen, and variably positive for VS38c and CD43. In each case the immunoglobulin profile and the light-chain type expression of the neoplastic cells were the same as those identified in the serum of the patients: 5 cases were IgA lambda; 2 cases were IgG kappa; and 1 case was IgA kappa. In cases 2, 3, and 4, polymerase chain reaction investigations revealed monoclonal rearrangement for IgH genes, whereas the investigations for human herpesvirus 8 and Epstein-Barr virus yielded negative results. Fluorescent in situ hybridization investigations in these 3 cases demonstrated that the cutaneous neoplastic plasma cells showed the deletion of the rb-1 (retinoblastoma) gene. Despite aggressive chemotherapy, all 8 patients died a few months after the development of cutaneous involvement. In our series, there was a perfect correlation of immunoglobulin and light-chain type between the serum electrophoresis and the cutaneous plasma cells. Patients with MM showed a short survival once cutaneous metastases appeared independently of the therapy. The deletion the rb-1 gene may provide prognostically relevant information to identify a high-risk subset of patients with MM.

Conflicts of interest: None declared. Sir, Papillon–Lefèvre syndrome (PLS) is an autosomal recessive genodermatosis mainly characterized by early‐onset periodontitis and palmoplantar keratoderma. Recurrent pyogenic skin infections, usually of mild degree and self‐healing, are relatively common additional features.1, 2 PLS is caused by loss‐of‐function mutations in the CTSC gene, which encodes for cathepsin C, a lysosomal cysteine protease required for the activation of granule‐associated serine proteases in immune/inflammatory cells.3 Cathepsin C consists of four identical subunits, each composed of three distinct polypeptide chains, the heavy chain, light chain and the N‐terminal fragment, held together by noncovalent interactions. The heavy and light chains form a two‐domain papain‐like structure, which contains the catalytic site, whereas the N‐terminal fragment shapes the ‘exclusion’ domain, which is crucial for substrate binding and selectivity.4 More than 60 distinct CTSC mutations have been identified, most of which are missense mutations that alter protein folding and function.5 We report a 24‐year‐old Italian woman, who underwent dermatological evaluation for recurrent pyoderma. She was the only affected child of healthy nonconsanguineous parents. Primary dentition was normal. In infancy, the gingiva surrounding the erupted teeth started to become inflamed with consequent premature tooth loosening. All remaining deciduous teeth were extracted before spontaneous exfoliation. The first permanent tooth erupted at 6 years of age. Progression of periodontal disease was slow, requiring extraction of only two permanent teeth. At the age of 4 years, multiple suppurative and inflamed skin lesions appeared on the cheeks and, subsequently, involved most of the body surface. These lesions had a protracted course and healed with scar formation. Since childhood the patient has complained of multiple and painful plantar callosities. Examination of the oral cavity revealed gingival inflammation and recession, and slight tooth mobility (Fig. 1a). A panoramic radiograph revealed bone resorption of mild to moderate degree around the teeth. In addition, the patient exhibited multiple callosities and minimal diffuse erythema of the soles (Fig. 1b,c). Palmar skin appeared slightly xerotic. Mild longitudinal ridging was also evident on the fingernails. Over the buttocks, thighs and calves, there were numerous polymorphic scarring lesions at sites of previous pyogenic infections. The most recent lesions appeared as violaceous nodules and plaques, while the oldest ones were hypopigmented and atrophic scars frequently showing subcutaneous fat herniation (Fig. 1d,e). A 10‐month course of isotretinoin (0·5 mg kg−1 daily) improved both the skin infections and the plantar keratoderma.

Merkel cell carcinoma (MCC) is a rare, rapidly growing, and highly malignant cutaneous tumor that typically presents in elderly males as an erythematous or violaceous plaque or nodule in sun-exposed areas. Risk factors include long-term ultraviolet (UV) exposure, Merkel cell polyomavirus (MCV) infection, immunosuppression, and lymphoproliferative disorders such as chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Given the aggressive nature of this tumor, patients may present with nodal and distal metastasis. Locoregional disease can be managed with definitive radiotherapy or surgery with or without adjuvant radiotherapy, depending on the case. Disseminated disease, on the other hand, often requires a multidisciplinary tumor board consultation to individually tailor the treatment. Possible treatments include systemic therapy with chemotherapy or immunotherapy, radiotherapy, and surgery. Here we report a case of a patient with a medical history significant for chronic lymphocytic leukemia and diffuse large B-cell lymphoma who presented with a rapidly growing lesion that contained neighboring MCC and CLL/SLL on biopsy. Management included immunotherapy with pembrolizumab and radiotherapy to limit the tumor's growth and spread. To the best of our knowledge, the coexistence of all three malignancies in a person is rare and has not been reported previously.

This abstract discusses an unusual rash caused by an atypical infection in a susceptible individual. A 52-year-old patient was referred in 2022 with a 12-month history of a progressive rash on the right leg with tender, inflamed and erythematous lesions. The patient had a background of severe relapsing polychondritis that was diagnosed in 2016. The disease was being managed with prednisolone 30 mg once daily, after previous failure of other immunosuppressive agents including methotrexate, azathioprine and 6 cycles of IV cyclophosphamide. Additionally, the patient was also on co-trimoxazole for Pneumocystis jirovecii pneumonia prophylaxis. On examination, erythematous and violaceous plaques and nodules were noted at the right leg with the lesions clustering and coalescing at the right medial thigh. A few of the lesions appeared infiltrated with pale material. Several warts were noted on the dorsal aspect of the hands, indicating significant immunosuppression. Differential diagnoses considered included the following: a vasculitic process, deposition disorders or an infective process. An urgent biopsy revealed palisaded granulomatous and neutrophilic dermatosis, indicative of an infectious aetiology. The patient was referred to the infectious diseases team. Acid alcohol-fast bacteria culture and whole-genome sequencing revealed a diagnosis of Mycobacteroides chelonae, a nontuberculous mycobacterium. The patient was commenced on 6 months’ treatment with combined doxycycline 100 mg twice daily and clarithromycin 500 mg twice daily. The patient responded well to treatment, with resolution of nodules on treatment completion. This case highlights the need for an increased index of suspicion in patients with a history of significant immunosuppression. Our patient had undergone QuantiFERON Gold (negative) in 2020 prior to IV cyclophosphamide. There is some evidence to suggest that QuantiFERON Gold may have the capacity to identify patients with nontuberculous mycobacteria (Kobashi Y, Mouri K, Yagi S et al. Clinical evaluation of the QuantiFERON-TB Gold test in patients with non-tuberculous mycobacterial disease. Int J Tuberc Lung Dis 2009; 13: 1422–6). There is robust guidance on TB infection screening prior to initiating immunosuppression (interferon-γ release assay and chest radiograph) [National Institute for Health and Care Excellence. Scenario: monitoring of DMARDs. Available at https://cks.nice.org.uk/topics/dmards/management/monitoring-of-dmards/ (last accessed 24 March 2024)]. However, there is a relative paucity of guidance related to infection monitoring after commencement of immunosuppression and the need for repeat QuantiFERON testing. Given the increasing use of complex chemotherapy and immunosuppression regimens in stan­dard practice, retaining a high index of suspicion for complex or atypical infection remains important and serves to highlight the need for appropriate investigation. Developing appropriate guidelines to rationalize infection monitoring of patients on long-term immunosuppression could further improve patient care.

Violaceous Plaques and Nodules: Challenge.

Violaceous Plaques and Nodules

Sweet’s syndrome associated with monosomy 7 myelodysplastic syndrome

AIDS-related Kaposi's sarcoma (KS) is the most common tumor arising in HIV-infected persons and is an AIDS-defining illness. Gastrointestinal (GI) involvement can occur in the presence or absence of cutaneous lesions and patients are often asymptomatic. We describe a case of KS with symptomatic extensive GI involvement after initiation of HAART and corticosteroid therapy. A 36 y/o homosexual Hispanic man with AIDS (CD4 of 31) presented to the ED with painful swallowing, fevers, night sweats and 5 lbs. weight loss over two weeks. He reported 6 months of diarrhea averaging 3 loose stools/day. HAART, high dose steroids, and Valganciclovir were started 4 months prior for AIDS, facial swelling and oral ulcers. Vital signs were T103.6 F, BP 102/54, PR 112, RR 20, and SpO2 of 100%. He had facial edema with violaceous plaques and nodules scattered across his face, dorsal tongue, torso and extremities, and oral ulcers. WBC 0.4 K/uL, Hgb 10.3 g/dL, and albumin of 1.4 g/dL. Antibiotics were given for neutropenic fever. Stool studies were negative for infection; positive FOBT. EGD revealed numerous erythematous nodules in the esophagus, stomach, and duodenum. Colonoscopy showed hemorrhagic nodules throughout the colon with multiple large ulcerations in the ascending colon. Biopsies revealed KS confirmed by human herpes virus 8 (HHV-8) immunostudy; CMV negative. Biopsies of skin and tongue were also positive for KS. Liposomal doxorubicin and filgrastim were started. Bone marrow biopsy was negative for HHV-8, infection, or malignancy. PEG tube was placed for malnutrition. Two cycles of Doxorubicin were completed. Odynophagia, diarrhea, and skin lesions resolved. He now tolerates solid food. KS is a vascular tumor associated with HHV-8. KS incidence significantly declined due to widespread use of HAART. KS usually presents with skin disease but can also involve a wide range of visceral organs including the GI and respiratory tract. Patients with GI involvement are often asymptomatic or may experience weight loss, abdominal pain, nausea and vomiting, GI bleeding, malabsorption, intestinal obstruction, or diarrhea. KS appears as hemorrhagic nodules sometimes with ulcerations. Biopsy shows whorls of spindle-shaped cells with leukocytic infiltration and neovascularization. Systemic chemotherapy is indicated for extensive cutaneous disease, symptomatic visceral disease, or cutaneous disease refractory to local therapy. Corticosteroids and infections have been associated with induction and worsening of preexisting KS. The high incidence of KS immediately following HAART may be due to the severe immunosuppression that led to HAART or to uncovering of KS by the immune reconstitution inflammatory syndrome. Chronic diarrhea in AIDS patients warrants endoscopy to evaluate for infectious causes and other diseases such as KS.Figure 1Figure 2Figure 3

Violaceous Plaques and Nodules: Answer.

Angiosarcoma of the skin: A clinicopathologic and fine structural study