Background and Aims

Neurofibromatosis is a genetic autosomal dominant disorder consisting in cutaneous, neurologic, ophthalmologic and tumoral signs. But other disorders that can mimic neurofibromatosis should be excluded.

Methods

A 10-year-old girl, from consanguineous gipsy parents, was admitted for anemia. Family history showed a sister who died due to cerebral tumors at the age of 3. The personal medical history was insignificant.

Results

The clinical examination revealed more than 6 „cafe au lait” spots larger than 0,5cm and multiple axillary freckling, signs which support the diagnosis of neurofibromatosis. The clinical exam of the parents was normal. Laboratory explorations showed a normochromic, normocytic anemia, with normal ferritin level, a folic acid deficiency, normal liver and kidney function, but also immunological abnormalities: IgA, IgG2 and IgG4 deficiency, poor response to vaccination, low memory B cells and a normal number of T, CD4+, CD8+ and NK cells. Ophthalmologic examination was normal. Multiple tumors with the diameter between 0,5 and 4 cm were noted during the cerebral MRI-scan. In evolution, she displayed recurrent episodes of seizures. The cerebral biopsy revealed a diffuse astrocytoma IDH mutant and she started chemotherapy. Taking in account the consanguinity, family history and the negative clinical exam of the parents we performed genetic exam – WES that revealed a pathogenic homozygous c.2653A>T mutation in MSH6 gene, parents being carriers for the same mutation.

Conclusions

In atypical cases of neurofibromatosis associating immunological abnormalities, DNA repair syndromes must be excluded. A correct diagnosis allows genetic counseling and monitoring for the cancer development in other members of the family.

Background and Aims

Primary immunodeficiencies(PIDs) are characterized by susceptibility to infections, autoimmunity but also cancer. Chromosome instability, chronic antigenic stimulation, tissue inflammation, impaired cell development and impaired immune surveillance may play a crucial role in the appearance of cancer in PIDs.

The aims of this study are to establish the frequency and evolution of the lymphoproliferative diseases in PIDs, in comparison with that of lymphoproliferative diseases without PIDs.

Methods

We analyzed 220 patients aged 0-18 years, diagnosed with PID in the period 1990 – 2018.

Results

18 patients (8,1%) developed lymphoproliferation (8 females and 10 males): 1 case with acute myeloblastic leukemia, 9 cases with non-Hodgkin lymphoma and 8 cases with lymphoproliferative disorders. The types of PID were: congenital neutropenia-1 case, ataxia-telangiectasia-1 case, hyperIgM syndrome-1 case, IgA deficiency-1 case, LRBA deficiency-1 case, TACI deficiency – 1 case, APDS- 1 case, CVID- 2 cases, combined immunodeficiency-2 cases, ALPS-2 cases and 5 cases with Nijmegen breakage syndrome. In 10 patients (55,5%) the onset of lymphoproliferative disorder preceded PID diagnosis. Treatment consisted in IVIg-11 patients, chimiotherapy-12 patients, G-CSF-2 patients and BMT-1 patient. 10 patients (55,5%) deceased. Mortality rate in patients with malignant lymphoproliferation was 70%. Mortality rate in 649 patients diagnosed (in the same clinic) with malignant hemopathies (AIDS patients were excluded) but without PIDs was 40,6%.

Conclusions

PIDs show a significantly higher incidence of lymphoproliferation. All patients with lymphoproliferation should be investigated for PID. The mortality rate was significant higher in patients with PIDs and malignant hemopathies in comparison with the patients with malignant hemopathies and without PIDs.