B-cell lymphoma associated with chronic lymphatic leukaemia: two cases with contrasting aggressive and indolent behaviour.

The term Richter's syndrome is used to describe the transformation of chronic lymphatic leukaemia (CLL) into a high-grade systemic lymphoma and is associated with a poor prognosis. We have undertaken detailed molecular studies in two patients with cutaneous B-cell lymphoma (CBCL) and CLL. Patient 1 exhibited a low-grade CBCL with different immunoglobulin gene rearrangements in blood and skin. By contrast, patient 2 showed identical gene rearrangements, confirmed by gene sequencing, and died within 4 months of presentation. The latter patient fulfilled the criteria for a diagnosis of cutaneous Richter's syndrome, whereas the former patient demonstrated the coincidence of CLL with a primary CBCL. Our results highlight the importance of gene rearrangement studies with sequencing for the accurate diagnosis of cutaneous Richter's syndrome.

The inherited palmoplantar keratodermas.

The inherited palmoplantar keratodermas (PPK) constitute a complex heterogeneous group of genodermatoses, which are difficult to classify clinically. The application of modern molecular biology techniques are leading to an increased understanding of the genetic bases of these disorders and are paving the way towards a classification based upon molecular pathology. We review the recent research advances in this field and the implications for development of novel approaches to disease management.

Reticulate acropigmentation of Dohi.

Two cases of reticulate acropigmentation of Dohi are reported, both patients demonstrating the typical features of this disorder. Reticulate acropigmentation of Dohi (dyschromatosis symmetrica hereditaria or symmetrical dyschromatosis of the extremities) is characterized by pigmented and depigmented macules mixed in a reticulate pattern on the extremities. It was first described in 12 patients from Japan, where it appears to be a well-established condition. Patients have been reported from Europe and a family from India has recently been described. We report two cases of reticulate acropigmentation of Dohi occurring in an Afro-Caribbean and an Indian patient, in order to alert clinicians to the possibility that this disorder may present in the UK.

Novel mutations in keratin 16 gene underly focal non-epidermolytic palmoplantar keratoderma (NEPPK) in two families.

Keratins K6 and K16 are expressed in suprabasal interfollicular epidermis in wound healing and other pathological conditions associated with hyperproliferation, such as psoriasis and are induced when keratinocytes are cultured in vitro. However, these keratins are also constitutively expressed in normal suprabasal mucosal and palmoplantar keratinocytes. Mutations in keratins have been reported in the basal keratin pair K5 and K14 in epidermolysis bullosa simplex and in suprabasal epidermal keratins K1, K2 and K10 in epidermolytic ichthyoses. Two families with autosomal dominant disorder of focal non epidermolytic palmoplantar keratoderma, have oral mucosal and follicular lesions in addition to the palmoplantar hyperkeratosis. Previous studies have shown linkage in these families to the type I keratin gene cluster at 17q12-q21 and this report shows that the cDNA of affected members of both families have novel heterozygous mutations in the expressed keratin 16 gene. These mutations (R10C and N8S) lie in the helix initiation motif of the 1A domain. These mutations do not appear to cause epidermolysis on light or electron microscopy, which may reflect differences in function, assembly or interaction of the 'hyperproliferative' or 'mucoregenerative' keratins from other major types of keratins. The mutations reported here are the first to describe the molecular pathology of focal non epidermolytic palmoplantar keratoderma.

O'Brien's actinic granuloma: response to isotretinoin.

We describe a 75-year-old man demonstrating the florid clinical features of actinic granuloma of O'Brien. This rare disfiguring condition is believed to result from a granulomatous reaction of the dermis to solar-induced elastosis and is poorly responsive to topical steroids. Twelve weeks' treatment with isotretinoin prevented the development of new granulomata and produced almost complete resolution of established lesions.

Ultrastructural changes resulting from keratin-9 gene mutations in two families with epidermolytic palmoplantar keratoderma.

Palmoplantar keratoderma of Voerner type (or epidermolytic palmoplantar keratoderma) is an autosomal dominant inherited disorder of keratinization with histologic features of epidermolytic hyperkeratosis. We studied members of two large unrelated kindreds with epidermolytic palmoplantar keratoderma, and biopsy specimens of lesional palmar skin from both families confirmed the histologic changes of epidermolytic hyperkeratosis. Whorls of abnormally aggregated keratin filaments were seen ultrastructurally to be associated with signs of cellular disintegration in spinous and granular cells. Direct sequencing of genomic DNA samples obtained from several members of each family established the substitution of a highly conserved arginine by tryptophan (R162W) in the 1A region of the alpha-helical rod domain of keratin 9. This arginine residue in a highly conserved region of keratins 1 and 10 is affected by disruptive missense point mutations in many patients with bullous ichthyosiform erythroderma. An equivalent position in the sole and palm restricted keratin 9 appears to be the mutation hot spot in epidermolytic palmoplantar keratoderma. To date, R162W is the most prevalent genetic defect reported in this genodermatosis.

Penicillamine-induced elastosis perforans serpiginosa treated successfully with isotretinoin.

Elastosis perforans serpiginosa (EPS) and the elastotic changes of pseudoxanthoma elasticum (PXE) are rare but well-recognized side-effects of long-term penicillamine therapy. A 42-year old female patient who developed both of these cutaneous side-effects following treatment with high-dose penicillamine for Wilson's disease is described; near-complete resolution of the EPS, but not the PXE was achieved by treatment with isotretinoin (0.5 mg/kg/day) for 6 weeks, despite continuation of the penicillamine.

Auricular embryonal rhabdomyosarcoma.

Rhabdomyosarcoma is an uncommon tumour that may present at a wide variety of different sites. We report a 4-year-old girl who developed an embryonal rhabdomyosarcoma arising in the left pinna which was clinically indistinguishable from a lymphangioma. The case illustrates that this neoplasm can be easily misdiagnosed because of its variable morphology. Early recognition is important as successful treatment is now possible with a combination of chemotherapy, surgery and/or radiotherapy.

Scleroderma and the carcinoid syndrome.

The follow up of a case of the carcinoid syndrome complicated by scleroderma is reported, in which progress of the disease may have been halted by treatment with a combination of cyproheptadine, parachlorophenylalanine and prednisolone. Impairment of tryptophan and 5-hydroxytryptamine (serotonin) metabolism appears central to the development of skin fibrosis in the carcinoid syndrome and may be indicative of important mechanisms in the pathogenesis of idiopathic scleroderma.