Biallelic inactivation of protoporphyrinogen oxidase and hydroxymethylbilane synthase is associated with liver cancer in acute porphyrias.

Variegate porphyria (VP) and acute intermittent porphyria (AIP), the two most common types of acute porphyrias (AHPs), result from a partial deficiency of protoporphyrinogen oxidase (PPOX) and hydroxymethylbilane synthase (HMBS), respectively. A rare but serious complication in the AHPs is hepatocellular carcinoma (HCC). However, the underlying pathomechanisms are yet unknown. We performed DNA sequence analysis in cancerous and non-cancerous liver tissue of a VP and an AIP patient, both with HCC. In samples of both cancerous and non-cancerous liver tissues from the patients, we identified the underlying PPOX and HMBS germline mutations, c.1082dupC and p.G111R, respectively. Additionally, we detected a second somatic mutation, only in the cancer tissue i.e., p.L416X in the PPOX gene of the VP patient and p.L220X in the HMBS gene of the AIP patient, both located in trans to the respective germline mutations. Both somatic mutations were not detected in 10 non-porphyria-associated HCCs. Our data demonstrate that in the hepatic cancer tissue of AHP patients, somatic second-hit mutations result in nearly complete inactivation of the enzymes catalyzing major steps in the heme biosynthetic pathway. Both PPOX and HMBS, which might act as tumor suppressors, play a crucial role in the development of HCC in these individuals.

[Vulvar lymphangioma circumscriptum: diagnosis and treatment]. / Het vulvaire lymfangioom.

BACKGROUND: The vulvar form of lymphangioma circumscriptumis a rare condition. It is part of the acquired lymphangiectasia and arises secondary, for example, after surgery, radiotherapy for malignancies in the pelvic region, inflammation in which vulvar lymphedema occurs or Morbus Crohn. CASE DESCRIPTION: A 44-year-old woman presented to the gynaecology outpatient department with a vulvar abnormality that was accompanied by pain and pruritus. Her medical history consisted of premalignant cervical abnormalities and a vulvar lichen simplex chronicus. A biopsy was taken and the diagnosis lymphangioma circumscriptum was made. Due to the growth and the complaints, the decision was made to remove the lesion in the operating room. CONCLUSION: Lymphangioma circumscriptum is a rare condition that is often misdiagnosed. This case may describe the development of lymphangioma circumscriptum from a lichen simplex chronicus, which has not been described before. It also demonstrates that surgical treatment appears to be a good treatment with few complications in the postoperative course.

Hepatocellular carcinoma in variegate porphyria: a serious complication.

Variegate porphyria is an acute hepatic porphyria resulting from a partial deficiency of protoporphyrinogen oxidase, the penultimate enzyme in haem biosynthesis. Cutaneous symptoms and acute neurovisceral attacks are well-known clinical characteristics of the disease. Less studied, however, is the risk of developing hepatocellular carcinoma, an aggressive type of liver cancer. We describe here two Swiss patients with variegate porphyria and this serious complication. Common risk factors, including alcohol over-consumption or chronic hepatitis, were absent in both patients. Interestingly, one patient carried mutation 1082-1083insC in the PPOX gene, a prevalent sequence deviation in the Swiss variegate porphyria population, which was also found in a French patient with variegate porphyria and hepatocellular carcinoma. Recent studies indicate that individuals with acute hepatic porphyria have a 36- to 61-fold increased risk of manifesting hepatocellular carcinoma. The incidence rate ratio in the Swiss population was estimated to be 34, comparable with those found in the French and Finnish populations. Because this tumour is associated with a rising mortality, we suggest regular screening for hepatocellular carcinoma in all patients with variegate porphyria.

Coincidence of cutaneous follicle center lymphoma and diffuse large B-cell lymphoma.

Primary cutaneous follicle center lymphoma (PCFCL) is a neoplasm with differentiation of centrocytes and centroblasts presenting in the skin. At the time of initial manifestation, extracutaneous involvement is absent. PCFCL is considered as an indolent variant of primary cutaneous B-cell lymphomas since dissemination to extracutaneous sites is rare and the prognosis is favorable. Here we describe a 30-year-old man who was diagnosed with a cutaneous FCL and did not show extracutaneous affection at the time of occurrence. Six months later, however, he developed a diffuse large B-cell non-Hodgkin lymphoma localized in several lymph nodes of the neck that most likely reflects the occurrence of a second primary tumor in the same patient.

Porphyria cutanea tarda in pre-existent lupus erythematosus--is there an association?

In lupus erythematosus (LE), vesicles and bullae are only rarely seen. However, in some instances such efflorescences might suggest an association with distinct cutaneous diseases, including erythema multiforme, toxic epidermal necrolysis or autoimmune blistering disorders such as bullous pemphigoid, pemphigus vulgaris, and dermatitis herpetiformis Duhring. Another blistering disease that has been described in association with cutaneous and systemic LE is porphyria cutanea tarda (PCT). PCT is a metabolic disorder caused by a deficiency of the fifth enzyme in heme biosynthesis, uroporphyrinogen decarboxylase. Here, we report on a 57-year-old Caucasian woman of Dutch origin with a medical history of mild cutaneous LE who developed skin fragility, blistering skin lesions, milia, and facial hypertrichosis. Subsequent porphyrin analysis in urine and feces confirmed the suspected simultaneous manifestation of LE and PCT.

Lichen planus with bullous manifestation on the lip.

A 75-year-old Caucasian female with a previous history of cutaneous lichen planus (LP) developed vesiculae and blisters on the lip. This special variant of oral LP is very rare and has to be distinguished from LP pemphigoides, bullous pemphigoid, pemphigus vulgaris, erythema multiforme, and herpes simplex virus infection. To date, there are only few reports on bullous oral LP on the lower lip. Although treatment is difficult, we successfully applied a topical combination of tretinoin 0.025% and triamcinolone 0.1%.