Novel NALCN biallelic truncating mutations in siblings with IHPRF1 syndrome.

Infantile hypotonia with psychomotor retardation and characteristic facies-1 (IHPRF1) is a severe autosomal recessive neurologic disorder with onset at birth or in early infancy. It is caused by mutations in the NALCN gene that encodes a voltage-independent, cation channel permeable to NM, K+ and Ca2+ and forms a channel complex with UNCSO and UNC79. So far, only 4 homozygous mutations have been found in 11 cases belonging to 4 independent consanguineous families. We studied a Sardinian family with 2 siblings presenting dysmorphic facies, hypotonia, psychomotor retardation, epilepsy, absent speech, sleep disturbance, hyperkinetic movement disorder, cachexia and chronic constipation. Polymorphic generalized seizures started at 4 and 6 years, respectively. Anti-epileptic drugs (AEDs) therapy was efficient for female proband's epilepsy, but the male still has weekly seizures. Whole exome sequencing identified 2 novel truncating mutations in NALCN allowing to assess the clinical phenotype to IHPRF1. This is the fifth family reported worldwide, and these are the first European cases with IHPRF1 syndrome with biallelic truncating mutations of NALCN.

Kikuchi-Fujimoto disease with lateral neck localisation: a case report.

The case is described of a Kikuchi-Fujimoto disease, in a 22-year-old female, onset of which was characterised by rapidly evolving lateral neck lymphadenopathy. Since clinico-radiological findings suggested a lymphoproliferative disease, it was mandatory, in order to establish the diagnosis and programme a suitable treatment protocol, to collect a lymph node biopsy specimen. The histological pattern was characteristic of Kikuchi-Fujimoto disease necrotizing lymphadenitis. Bearing in mind the difficulties encountered in the diagnosis of Kikuchi-Fujimoto disease, due not only to lack of a characteristic clinical pattern but also to the generic and aspecific findings emerging from radiological evaluation, the Authors stress the important role of histological examination in establishing the nature of the disease. In their opinion, onset of a rapidly evolving lateral neck lymphadenopathy, in a young patient, in the absence of well-defined disorders possibly responsible for the condition, and in order to establish a correct diagnostic approach, should induce the ENT specialist to take into consideration the possible presence of Kikuchi-Fujimoto disease, even if this is to be considered a rare finding.

Supraventricular tachyarrhythmias involving the sinus node: clinical and electrophysiologic characteristics.

Supraventricular tachyarrhythmias occur quite commonly and are now evaluated more often because of technological advances in the field of electrophysiology. Arrhythmias that involve the sinus node, namely, the syndrome of inappropriate sinus tachycardia and sinus node reentry, are rare. Because of their origin in the sinus node, the surface electrocardiogram (ECG) in these patients can present a diagnostic challenge to the clinician and in fact may elude recognition as an abnormal heart rhythm. Presented in this review are the clinical characteristics of these arrhythmias, as well as the mechanisms of action. Pharmacotherapy may be therapeutic in certain patients in preventing recurrences; however, radiofrequency catheter ablation offers a lifelong curative effect for these patients.

Acantholytic dyskeratotic epidermal naevus localized unilaterally in the cutaneous and genital areas.

A 38-year-old woman presented with unilateral lesions on the left side of the body and in the genital area. Clinically, the lesions showed a polymorphic pattern: brownish papules in the axilla, keratotic comedo-like papules on the hand and foot, and whitish papular plaques on the labia majora and anal canal. There was no family history of skin diseases. Histologically, cutaneous and mucosal specimens were characterized by acantholytic and dyskeratotic cells, corps ronds and grains in the parakeratotic zone, and by hyperkeratosis and parakeratosis. A diagnosis of epidermal naevus with acantholytic dyskeratosis was made.

[Kikuchi's disease and proteinaceous lymphoadenopathy in 4 patients with HIV infection]. / Malattia di Kikuchi e linfoadenopatia proteinacea in quattro pazienti on infezione da HIV.

In the lymphadenopathy occurring in the acquired immunodeficiency syndrome (AIDS) and the AIDS related complex (ARC), consistent histologic patterns have been described with some variants thereof, such as angioimmunoblastic lymphadenopathy-like or Castleman disease-like. In four such patients we have observed two other types of nodal lesions. Three patients had lymph node biopsies showing the characteristic histologic and immunophenotypic features of histiocytic necrotizing lymphadenitis (Kikuchi's disease). These were two males, 26 and 35-year old, with bilateral axillary and cervical lymphadenopathy, respectively, and one female, 29-years old with peripheral and abdominal lymphadenopathy. One patient had proteinaceous lymphadenopathy. This was a 26-year old man with disseminated lymphadenopathy and a small monoclonal IgG/k peak in the serum. Whether these two processes are direct effects of the HIV virus on the immune system or due to intercurrent etiologic factors, has to be determined. These observations, however, indicate that the range of nodal lesions (that the pathologist may encounter) in AIDS/ARC is wider than previously reported.

Lymphangioma-like variant of Kaposi's sarcoma: clinicopathologic study of seven cases with review of the literature.

The clinical and pathological features of seven cases of lymphangioma-like Kaposi's sarcoma (KS) are reported. As with the other subtypes of KS, the lymphangioma-like variant occurs more often in men aged 59-80 years. Clinically, the lesion appears intermingled with the classical forms of KS, but a "bulla-like" appearance recognized in seven of 13 cases has been considered as a clinical hallmark of this variant. Although occasional cases have shown aggressive behavior, the most frequent clinical course is slowly progressive with localized or diffuse involvement of lower limbs. The histological pattern, characterized by permeation of dermal collagen by labyrinthine vascular channels lined by a flattened endothelium, must be differentiated from spindle cell hemangioendothelioma, low-grade angiosarcoma, targetoid hemosiderotic hemangioma, and benign lymphangioendothelioma.

Primary spindle cell tumor of lymph node with "amianthoid" fibers: a histological, immunohistochemical and ultrastructural study.

A primary mesenchymal spindle cell tumor with amianthoid fibers was observed in an inguinal lymph node of a 70-year-old woman. With immunohistochemical stains the cells were positive for muscle actin and negative for desmin. Transmission electron microscopy (TEM) showed intracytoplasmic bundles of microfilaments with focal densities, profiles of rough endoplasmic reticulum, and basementlike material indicative of myofibroblastic and/or smooth-muscle cell differentiation. At scanning electron microscopy (SEM) the tumor was organized into slitlike spaces containing red blood cells. Amianthoid fibers showed a strong positivity for actin at their edge with a central negative core; by TEM they appeared to be formed of 200 nm thick crystallized collagen fibers surrounded by actin microfilaments arranged in a palisading fashion. The immunohistochemical and ultrastructural findings of the proliferating myoid cells suggest a possible derivation from smooth-muscle vascular cells. Collagen fiber aggregation and actin filament dismission might be secondary to anoxia due to vascular obliteration or disruption.

Rhabdoid tumours of the central nervous system. Report of three cases with immunocytochemical and ultrastructural findings.

Three cases of rhabdoid tumour of the central nervous system arising in a supratentorial location are reported. The patients were 18, 14, and 7 years old. All three tumours showed a common morphology. The neoplastic cells were usually globoid with round nuclei and prominent nucleoli and large acidophilic, cytoplasmic inclusions were present in many of them. These inclusions showed strong immunoreactivity for vimentin, weak immunoreactivity for epithelial membrane antigen and focal immunoreactivity for cytokeratins. Ultrastructurally they were made up of whorls of intermediate filaments, 8-10 nm in thickness. Rhabdoid tumours of the central nervous system, whatever the cell of origin, appear to be an independent entity with identifiable histology and aggressive behaviour.

Familial insulinoma: description of two cases.

We describe cases of isolated functioning insulinoma occurring in two members of the same family (father and daughter). The father had a first encapsulated insulinoma diagnosed at 14 years of age and at the age of 33 years he was operated on for a second insulinoma infiltrating the exocrine pancreas with lymph node metastases. The daughter was operated on for an encapsulated insulinoma in the tail of the pancreas when she was 6 years old. No clinical and laboratory signs of other endocrine disturbances have so far been detected in either care or in any other members of the family. Our report suggests the possibility of multiple familial insulinoma, although this is an extremely rare condition. Our data also indicate that insulinomas, even if well controlled by medical treatment, should always be removed by surgery because malignancy cannot be excluded with certainty. Moreover, patients should be closely followed up, as recurrence may develop up to 15 years after surgery.