No abstract

Spitz neoplasms, according to 2018 WHO Blue Book, are morphologically defined by spindled and/or epithelioid melanocytes and genetically by either HRAS mutations or kinase gene fusions. The terminology "spitzoid" refers to lesions with similar morphology but with alternate or undefined genetic anomalies. Herein, we present 3 melanocytic neoplasms with a spitzoid cytomorphology, variable nuclear atypia, and harboring undescribed fusions involving RASGRF1. Two cases presented as unpigmented papules on the heel of a 26-year-old female (case 1) and the forearm of a 13-year-old boy (case 2). They were classified as low-grade melanocytomas (WHO 2018). The third case appeared as a pigmented ulcer on the sole of a 72-year-old female (case 3) that displayed diagnostic features of an invasive melanoma (Breslow thickness 6 mm, Clark level V). A wide skin reexcision identified an epidermotropic metastasis, and sentinel lymph node biopsy displayed multiple subcapsular metastatic deposits. RNA sequencing revealed CD63::RASGRF1, EHBP1::RASGRF1, and ABCC2:: RASGRF1 fusions in cases 1 to 3, respectively. They were confirmed by a RASGRF1 break-apart fluorescence in situ hybridization technique. Translocations of RASGRF1, a gene coding a guanine nucleotide exchange factor but not a kinase, have rarely been reported in tumors. While all these cases showed spitzoid cytomorphology, it is too early to tell if they are true Spitz neoplasms as currently defined.

A 52-year-old woman was referred for a retroperitoneal mass, the biopsy of which revealed follicular lymphoma. Before admission, she had developed a polymorphic bullous eruption and painful oral ulceration. Examination showed several oral ulcers (especially on the lateral surfaces of the tongue and on the cheeks), gingivitis and erosions of lips with adherent whiteyellow exudate (top left). There were numerous erosions with erythematous bases on the trunk, from 0AE5 to 3 cm in diameter, with crusts, multiple flaccid or tense blisters and lichenoid lesions suggestive of erythema multiforme (top right). Conjunctivitis with yellowish secretions was present (bottom left).Skin biopsy showed suprabasal and subepidermal clefts with scattered necrotic keratinocytes (bottom right). Eosinophilic infiltration of dermis and epidermis and epidermal acantholysis were observed. Direct immunofluorescence (IF) studies showed deposition of IgG and C3 on the surface of keratinocytes and in the basement-membrane zone. Indirect IF studies showed binding of serum antibodies to rat bladder. The patient's serum was positive for anti-desmogleins 1 and 3 antibodies by enzyme-linked immunosorbent asssay.The diagnosis of paraneoplastic pemphigus was established. A spectacular improvement of skin lesions was observed following the first cycle of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone). Oral ulcerations were much more resistant to treatment despite obtaining a very good haematological partial response after four cycles and maintenance of steroids. After eight cycles, oral improvement was finally observed. As paraneoplastic pemphigus requires specific and prolonged therapy, the diagnosis of this life-threatening affection should be considered by haematologists when faced with polymorphous eruption and oral ulcerations.

The prevalence of depression is higher in patients with inflammatory bowel disease (IBD) than in the general population. Women are more significantly affected by depression among those with IBD and in the general population. This review presents evidence on sex-based differences in depression pathogenesis and the effect of depression on various factors associated with IBD that affect women’s lives, including sexual dysfunction, body image dissatisfaction, fertility, and overall quality of life. We also discuss sex-specific effects on IBD treatment, disease activity, and health care costs. Interestingly, women with IBD tend to seek and are more receptive to depression-related information. Given the underdiagnosis and undertreated nature of depression in individuals with IBD, effective screening and an optimal integrative treatment approach with relevant sex-specific needs are discussed. Evidence regarding the efficacy of psychotherapy, antidepressant pharmacotherapy, and IBD-specific therapy for depression is discussed. This review summarizes evidence of the effect of depression on both personal and professional aspects of the daily lives of women with IBD, which extends beyond negative moods. It applies this information to screening and integrative treatment, resulting in a holistic approach to this multidimensional problem. We also discuss how depression affects males with IBD differently from females. Finally, we discuss the need for gender-based studies on depression in individuals with IBD.