Evaluation of universal immunohistochemical screening of sebaceous neoplasms in a service setting.

BACKGROUND: Muir-Torre syndrome (MTS) is a subtype of Lynch syndrome, which encompasses the combination of sebaceous skin tumours or keratoacanthomas and internal malignancy, due to mutations in DNA mismatch repair genes. Sebaceous neoplasms (SNs) may occur before other malignancies, and may lead to the diagnosis, which allows testing of other family members, cancer surveillance, risk-reducing surgery or prevention therapies. AIM: To evaluate the efficacy of universal immunohistochemistry (IHC) screening of SNs in a service setting. METHODS: Patients with SNs were ascertained by a regional clinical pathology service over a 3-year period. Results of tumour IHC, clinical genetics notes and germline genetic testing were retrospectively reviewed. RESULTS: In total, 62 patients presented with 71 SNs; 9 (15%) of these patients had previously diagnosed MTS. Tumour IHC was performed for 50 of the 53 remaining patients (94%); 26 (52%) had loss of staining of one or more mismatch repair proteins. Fifteen patients were referred to the Clinical Genetics department, and 10 patients underwent germline genetic testing. Two had a new diagnosis of MTS confirmed, with heterozygous pathogenic mutations detected in the MSH2 and PMS2 genes (diagnostic yield 20%). The PMS2 mutation was identified in a 57-year-old woman with a sebaceous adenoma and history of endometrial cancer; to our knowledge, this is the first time a PMS2 mutation has been reported in MTS. CONCLUSIONS: Universal IHC screening of SNs is an effective method to identify cases for further genetic evaluation. Rates of referral to clinical genetics were only moderate (58%). Increased awareness of MTS could help improve the rate of onward referral.

Immunobullous dermatosis associated with Waldenström macroglobulinaemia treated with rituximab.

Waldenström macroglobulinaemia (WM) is a chronic lymphoproliferative disorder characterized by the presence of a monoclonal IgM paraprotein. Specific cutaneous features of WM include neoplastic cell infiltrates, IgM storage papules and IgM bullous dermatosis. We report a patient with subepidermal bullous disease associated with WM. Immunofluorescence identified IgM deposition along the basement membrane zone (BMZ) with circulating anti-BMZ IgM antibodies reacting with the dermal side of salt-split skin. The autoantibodies did not react with type VII collagen or laminin 332. Following failed treatment with doxycycline, prednisolone, intravenous immunoglobulin and dapsone, the patient was successfully treated with a modified RCVP regimen (rituximab, cyclophosphamide and prednisolone). To our knowledge, this is the first reported case of IgM bullous disease of WM treated with rituximab.

Immunoglobulin G4 related systemic sclerosing disease involving the temporal bone.

OBJECTIVE: To report a rare condition affecting the temporal bone. Immunoglobulin G4 related systemic sclerosing disease is a recently described autoimmune condition with manifestations typically involving the pancreas, biliary system, salivary glands, lungs, kidneys and prostate. Histologically, it is characterised by T-cell infiltration, fibrosis and numerous immunoglobulin G4-positive plasma cells. This condition previously fell under the umbrella diagnosis of inflammatory pseudotumour and inflammatory myofibroblastic tumour. CASE REPORT: We present the case of a 58-year-old woman with multiple inflammatory masses involving the pharynx, gall bladder, lungs, pelvis, omentum, eyes and left temporal bone, over a seven-year period. We describe this patient's unusual clinical course and pathological features, which resulted in a change of diagnosis from metastatic inflammatory myofibroblastic tumour to immunoglobulin G4 related systemic sclerosing disease. We also review the literature regarding the management of inflammatory pseudotumours of the temporal bone, and how this differs from the management of immunoglobulin G4 related systemic sclerosing disease. CONCLUSION: We would recommend a full review of all histological specimens in patients with a diagnosis of temporal bone inflammatory pseudotumour or inflammatory myofibroblastic tumour. Consideration should be given to immunohistochemical analysis for anaplastic lymphoma kinase and immunoglobulin G4, with measurement of serum levels of the latter. Management of the condition is medical, with corticosteroids and immunosuppression, rather than surgical excision.

Multiple primary malignancies in patients with Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare malignant cutaneous tumour, the incidence of which is increasing. Second malignancies have been reported to occur with high incidence in these patients. OBJECTIVES: We report the rate and nature of multiple malignancies in patients with MCC treated over a 10 year period in Addenbrooke's Hospital in Cambridge, United Kingdom, as well as the temporal relationship of these additional malignancies to the diagnosis of MCC. RESULTS: The 27 patients had an approximately equal sex incidence with a median age at diagnosis of 79 years. Seventy percent (n=19) of patients had a second primary malignant tumour; and 7 of these patients had two or more tumours in addition to the MCC. Eighteen patients had additional cutaneous malignancies: melanoma, squamous cell carcinoma and basal cell carcinoma, and 8 patients presented non-cutaneous malignancy including colorectal, haematological and breast tumours. Of the 28 additional tumours in our patients, half were diagnosed prior to presentation of MCC, 32% within 6 months of diagnosis, and 18% between 6 months and 3 years after diagnosis. Possible reasons for the high rate of additional tumours in this population are discussed. CONCLUSIONS: Our figures reflect a higher incidence of multiple malignancies in those with Merkel cell tumour than has previously been reported. This has important implications for the care and surveillance of these patients.

Generalized granuloma annulare in a photosensitive distribution resolving with scarring and milia formation.

We describe an unusual case of generalized granuloma annulare (GA) in a 70-year-old man. This occurred in a photosensitive distribution, responded rapidly to topical and systemic treatment, and resolved leaving residual scarring and milia. To our knowledge, this is the first report of the occurrence of milia formation and scarring in association with GA.

Hidradenitis suppurativa, Dowling-Degos and multiple epidermal cysts: a new follicular occlusion triad.

This case illustrates the rare association between hidradenitis suppurativa (HS) and Dowling-Degos disease (DDD). Furthermore the association of HS, DDD and multiple epidermal cysts has not to our knowledge been described before, but their coexistence in the same patient is likely to reflect the same follicular anomaly. It is possible that a single underlying defect of follicular proliferation may account for the coexistence of these conditions.

Elastophagocytosis: a feature of resolving Sweet's syndrome.

We report the case of a patient with atypical Sweet's syndrome characterized by an annular erythema that showed consumption of elastic fibres by giant cells and histiocytes. Although the lesions were found on sun-exposed sites and the first biopsy demonstrated extensive elastophagocytosis, our patient did not have photodamaged skin clinically. A repeat biopsy 5 weeks later demonstrated an abundant collection of neutrophils supporting the diagnosis of Sweet's syndrome. To our knowledge, an elastolytic granulomatous reaction pattern has not been previously reported in Sweet's syndrome.

Pustular pyoderma gangrenosum.

Pyoderma gangrenosum (PG) is an idiopathic inflammatory disease of unknown aetiology, frequently associated with an underlying systemic condition such as inflammatory bowel disease or haematological malignancy. Its occurrence tends to parallel exacerbations of the underlying disease. Four clinical variants of PG have been described and these include ulcerative, pustular, bullous and vegetative types. We report two cases of the pustular form, which is an uncommon variant of PG, where the pustules do not progress to form ulcers. Both our patients suffered with inflammatory bowel disease which remained quiescent as the pustular PG developed.