Squamous cell carcinoma in a child with Clericuzio‐type poikiloderma with neutropenia

MADAM, Poikiloderma with neutropenia (PN) is a rare disorder attributed to mutations in the USB1 gene, with many similarities to other hereditary poikilodermas (HP). The risks ascribed to this condition are yet to be fully elucidated. We report the case of a patient with PN who developed a squamous cell carcinoma (SCC) of the toe at an early age, and we include studies demonstrating abnormal neutrophil function. Our patient developed pigmented, reticulate skin lesions with atrophic change and telangiectasia on the arms, legs, face and trunk from the age of 3 months. Additional features include pachyonychia of the toenails, occasional mouth ulcers and plantar keratoderma. Distinctive facies were noted: a saddle nose, flat nasal bridge, flared nostrils and prominent forehead with some mid-face hypoplasia (Fig. S1; see Supporting Information). She was initially on the 25th centile for height and weight; however, this fell after her third year to her current stature below the 2nd centile for height and weight. Ophthalmology reviews have shown no abnormality. There is no history of photosensitivity, noting that the family lives in Cyprus. However, the patient has taken great care to avoid sun exposure, using high factor sun protection cream and covered shoes whenever outside. The initial diagnosis was considered to be Rothmund– Thomson syndrome; however, she had a normal karyotype and no evidence of a RECQL4 mutation. A persistent neutropenia became apparent from the age of 3 years. This was associated with frequent admissions for infections requiring intravenous antibiotics, and necessitating the initiation of granulocyte colony stimulating factor (GCSF) at 5 years. A diagnosis of PN was made and genetically proven. Direct sequencing shows the patient to be homozygous for a USB1 gene mutation. Mutation analysis revealed a point mutation 541C>T, protein Gln181X. The patient’s asymptomatic parents are heterozygous for this mutation. Her haemoglobin and platelet counts have remained low ⁄normal to low since first recorded at 2 years. Neutrophils have remained very low, in the absence of GCSF support. Recently she has relied on antibiotic prophylaxis, with GCSF for breakthrough infections only. She presented at 13 years with a nonhealing skin lesion on the right fourth toe (Fig S1; see Supporting Information). This was treated at an outside hospital as an infection, by debridement and repeat dressings, but with no improvement. She was subsequently evaluated at our institution 16 months after onset. Examination revealed the toe to be swollen and purple with no adjacent spread. Biopsy revealed it to be a SCC (Fig. 1). The fourth toe was amputated and healed well; 3 months postsurgery she has recovered completely. This patient had been referred to in the literature prior to the development of the SCC. Histology showed an acanthotic epidermis with hypergranulosis and compact hyperkeratosis (Fig. 1). A longitudinal section through the junction of the ulcerated area demonstrated an invasive well-differentiated SCC, with adjacent basal atypia that was completely excised by at least 4 mm. Neutrophil function studies have been performed twice. Phagocytosis of Escherichia coli and shedding of L-selectin in response to lipopolysaccharide or phorbol 12-myristate 13acetate (PMA) were normal. On both occasions patient neutrophils produced a significantly lowered respiratory burst when stimulated with PMA (8% of the median response in