Phakomatosis pigmentovascularis and Lisch nodules. Relationship between Von Recklinghausen and phakomatosis pigmentovascularis?

In 1947, Ota described a malformative syndrome associating a vascular component (nevus flammeus) with melanocytic or epidermic nevi, which he named phakomatosis pigmentovascularis (PPV). We will discuss the case of a 10-year-old boy presenting giant nevus flammeus, nevus spillus, asymmetry in the development of both lower limbs, characteristic of PPV, together with interventricular communication and Lisch nodules, representative of Von Recklinghausen's disease. We believe that this case can be classified as PPV type IIb, associated with Lisch nodules and rarely described in Caucasian individuals.     

Pure sclerotic neurofibroma: a neurofibroma mimicking sclerotic fibroma

BACKGROUND: Neurofibroma (NF) is a benign tumor of the nerve sheath. Several variants of NF have been described. PURPOSE: We report a case of NF with sclerotic changes resembling sclerotic fibroma (SF). METHODS AND RESULTS: The patient was a 61-year-old man who had an asymptomatic cutaneous lesion on the right scapular region. Physical examination revealed a pedunculated, white-to-pinkish nodule that had a firm consistency, spherical morphology, and smooth surface. Microscopically, the nodule showed a well-circumscribed, nonencapsulated dermal tumor composed of scant cells and thick collagen bundles with prominent clefts. The tumor cells were immunoreactive for vimentin and S100 protein. The patient was diagnosed as having pure sclerotic NF. To our knowledge, only five cases of NF with SF-like pattern have been previously published, and in two this pattern was pure. CONCLUSION: It is important to recognize this exceptional type of NF because it may be easily confused with SF, as well as with a wide variety of neoplasms or hamartomatous conditions containing similar sclerotic pattern.     

Association of piebaldism and neurofibromatosis type 1 in a girl

We report an 11-year-old girl with both piebaldism and neurofibromatosis type 1 (NF1). The patient had large depigmented patches on her lower limbs and a white forelock since birth. In addition, some café au lait spots were present on her trunk at birth and had increased in number and size during childhood in concomitance with the appearance of axillary and inguinal freckling. Neither neurofibromas nor Lisch nodules were detected and the patient was otherwise healthy. Pedigree analysis revealed inheritance for piebaldism on the paternal side. To our knowledge, the association of piebaldism and NF1 has been described previously in only three patients. Awareness of this rare association is relevant to ensure early diagnosis and adequate follow-up for NF1.     

Giant café-au-lait macule in neurofibromatosis 1: a type 2 segmental manifestation of neurofibromatosis 1?

Type 2 segmental manifestation of autosomal dominant dermatoses refers to pronounced segmental lesions superimposed on the ordinary nonsegmental phenotype, indicating loss of heterozygosity occurring at an early stage of embryogenesis. We describe a 20-year-old Taiwanese woman with typical lesions of neurofibromatosis type 1 (NF1) in the form of characteristic café-au-lait spots, neurofibromas, axillary freckling and Lisch nodules. In addition, a giant garment-like or "bathing-trunk" café-au-lait macule involved the lower half of the trunk, the buttocks, and parts of the thighs, being superimposed on the ordinary smaller spots of NF1. This large café-au-lait macule may be best explained as an example of type 2 segmental NF1. A novel mutation (3009delG) in exon 23 was also identified in this patient, which has not yet been described in sporadic and familial NF1.     

Bilateral segmental neurofibromatosis with gastric carcinoma

Neurofibromatosis type 1 (NF1) is an autosomal-dominant disorder characterized by café-au-lait spots, neurofibromas, intertriginous freckles, and Lisch nodules in the iris. Segmental neurofibromatosis is fundamentally a mosaic variant of NF1. A 66-year-old man visited us with bilateral segmental neurofibromatosis (SN) on the torso. He had multiple neurofibromas on the back bilaterally and on the right abdomen, and partial unilateral lentiginosis on the left abdomen and left back. The patient had noticed the development of papules and nodules on the right abdomen and bilaterally on the back 6 years previously, and had been diagnosed with early gastric carcinoma 5 years previously. To our knowledge, this is only the third reported case of SN associated with internal malignant tumours.     

Inflammatory Nodules of the Leg

There is a group of diseases characterized by inflammatory nodules which generally located on the lower leg. They have certain clinical appearances in common, which often makes a differential diagnosis difficult or impossible on clinical grounds alone. There is a great variation in histopathologic appearance, which depends on the duration of the lesions and sites from specimens are obtained for biopsy. Therefore, separating and subclassifying inflammatory nodule lesions of the legs, based on the subtle clinical and histological variation, is not easy. Despite all these difficulties, a specific diagnosis can be made with an adequate clinic-pathologic correlation.     

Epidermodysplasia verruciformis associated with neurofibromatosis type 1: coincidental association or model for understanding the underlying mechanism of the disease?

We describe a 25-year-old man with epidermodysplasia verruciformis (EV) associated with neurofibromatosis type 1 (NF1). The lesions, persisting for more than 15 years, consisted of widespread planar warts on the backs of the hands and wrists, and reddish-brown macules on the trunk, neck and face. During the last 5 years, our patient developed several epithelial tumours, namely solar keratoses, plaques of Bowen's disease and squamous cell carcinomas (SCCs). He also presented with NF1 lesions with neurofibromas, café-au-lait macules, axillary freckling and Lisch nodules. He had left tibial bowing. Polymerase chain reaction analysis of the skin lesions demonstrated the presence of human papillomavirus (HPV) 15 in a flat wart, HPV 20 in a plaque of Bowen's disease, and HPV 15 and HPV 20 in an SCC lesion. Both EV and NF1 show an inherited predisposition to malignancy but the molecular mechanism underlying tumour development is not fully understood. The appearance of both diseases in our patient may be a coincidental association but may also contribute to the identification of loci for susceptibility to NF1 and EV on chromosome 17.     

Segmental neurofibromatosis

A 74-year-old man presented with skin-colored nodules in his left antecubital fossa. The lesions had been present for 35 years and were asymptomatic. Nodules elsewhere on the body, cafe-au-lait spots, axillary freckling, and Lisch nodules were absent. No family members had similar nodules. A diagnosis of segmental neurofibromatosis was made, and a biopsy specimen of a nodule showed a neurofibroma. As the patient had no complications of neurofibromatosis 1, no treatment was needed.     

Dermoscopy of the iris: identification of Lisch nodules and contribution to the diagnosis of neurofibromatosis type 1

Neurofibromatosis is a common genodermatosis, whose diagnosis often involves the participation of a dermatologist. A case of a 38-year-old female patient with four café-au-lait macules and eleven neurofibromas on clinical examination is presented. Dermoscopy allowed the identification of Lisch nodules in the iris, bilaterally. The combination of these findings allowed the diagnosis of neurofibromatosis type 1, according to NIH criteria. Lisch nodules are melanocytic hamartomas of the iris, which must be evaluated through a visual augmentation method, usually employed in ophthalmology. Alternatively, dermoscopy can be used and contribute to the early diagnosis of neurofibromatosis type 1.     

Clinical features of 58 Japanese patients with mosaic neurofibromatosis 1

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder caused by mutation in the NF1 tumor‐suppressor gene, and may sometimes manifest in a mosaic form. “Segmental NF1” is generally assumed to be the result of somatic mosaicism for a NF1 mutation, and patients with mosaic NF1 have typical features of NF1 limited to specific body segments. The clinical features of 58 patients (42 females and 16 males; aged 1–69 years; mean age, 23.4 years) with mosaic NF1 seen at the Jikei University Hospital during 2004–2007 and at the Jikei University Daisan Hospital during 2007–2011, were retrospectively studied. Somatic or gonosomal mosaicism was not investigated. Patients were classified into four groups: (i) pigmentary changes (café‐au‐lait spots and freckling) only (n = 32); (ii) neurofibromas only (n = 5); (iii) neurofibromas and pigmentary changes (n = 13); and (iv) solitary plexiform neurofibromas (n = 8). The area of involvement was variable. The majority of patients were asymptomatic, except patients with plexiform neurofibromas who presented most commonly with pain or tenderness. Lisch nodules were rarely seen. Only four of our 58 patients (6.9%) had specific NF1 complications, including language delay (n = 1) and bone deformity (n = 3). Two patients were ascertained through their children with generalized NF1. Patients with mosaic NF1 are at low risk of developing disease‐associated complications, except patients with plexiform neurofibromas. However, they need to be aware of the small risk of having a child with generalized NF1.     

Neurofibromatosis--review of the literature and case report

Neurofibromatoses are genetic disorders of the nervous system that primarily affect the development and growth of neural (nerve) cell tissues. These disorders cause tumors to grow on nerves, and produce other abnormalities such as skin changes and bone deformities. Although many affected persons inherit the disorder, between 30 and 50 percent of new cases arise spontaneously through mutation in the individual's genes. We report on seven cases of type 1 neurofibromatosis (NF1) diagnosed from 2001 to 2006 at our Department. There were four female and three male patients, mean age 46.1 and 49 years, respectively. All patients showed neurofibromas accompanied by fibromas, café au lait spots, cases showed five axillary freckling (lentigines) and one case showed five plexiform neurofibromas and pruritus belonging to NF1 category. All patients had affected first degree relatives. Systemic findings were rare and included optic glioma in one case and Lisch hamartoma nodules in three cases. In all cases, the diagnosis was established according to the National Institutes of Health criteria, including at least two of the diagnostic criteria for NF1 diagnosis. None of our cases had malignancies or gastrointestinal tract involvement.     

Neurofibromatosis of atypical presentation

Neurofibromatosis (NF) is considered to be a heterogeneous neuroectodermal disease clinically defined by the presence of neurofibromas, multiple café-au-lait spots, intertriginous freckles and Lisch nodules. Mosaicism explains atypical presentations of the disease. Early mutations, before tissue differentiation, give rise to generalized disease. We report an atypical presentation of neurofibromatosis with an unusual distribution of neurofibromas, a peculiar, clinically and pathologically, neurofibroma on the trunk and the association with an ovarian serous cystoadenofibroma.     

Mosaic neurofibromatosis type 1

A 24-year-old man presented with numerous lentigines and multiple cafe-au-lait macules on both sides of the face, neck, and trunk as well as on the proximal area of the upper extremities and in the axillae. The pigmented lesions had a Blaschko-linear distribution on the upper trunk and were limited to the left side of the abdomen, with a sharp demarcation at the midline. Multiple, cutaneous neurofibromas were found on the trunk, and ophthalmologic examination showed a Lisch nodule in the left iris. The clinical findings and their widespread but segmental distribution were consistent with a diagnosis of mosaic neurofibromatosis type 1.     

Genetic analyses of mosaic neurofibromatosis type 1 with giant café-au-lait macule,plexiform neurofibroma and multiple melanocytic nevi

Neurofibromatosis type 1 (NF1) is a genodermatosis caused by heterozygous germ line variations in the NF1 gene. A second-hit NF1 aberration results in the formation of café-au-lait macules, cutaneous neurofibroma and plexiform neurofibroma (PNF). Mosaic NF1 (mNF1), caused by a postzygotic NF1 mutation, is characterized by localized or generalized NF1-related manifestations. Although NF1 and mNF1 are associated with pigmentary skin lesions, clinically recognizable melanocytic nevi that developed over PNF have not been reported. Here, we report the first case of multiple melanocytic nevi that developed on a giant café-au-lait macule and PNF. The PNF had biallelic NF1 deletions, a whole deletion of NF1 and a novel intragenic deletion involving exons 25–30. The deletions were not detected in the blood, which resulted in the diagnosis of mNF1. Furthermore, the nevus cells had not only biallelic NF1 deletions but also NRAS Q61R, a common mutation found in congenital melanocytic nevi. These analyses revealed the coexistence of the two different mosaic diseases, mNF1 and congenital melanocytic nevi. For a diagnosis of cases with atypical NF1-like symptoms, genetic analyses using blood and lesional tissues are useful and aid in genetic counseling.     

Diffuse cutaneous calculi (subepidermal calcified nodules): Case study

Four forms of calcinosis cutis exist: metastatic calcinosis, dystrophic calcinosis, idiopathic calcinosis, and subepidermal calcified nodules, usually referred to as cutaneous calculi because single, small, raised, hard nodules are present. Occasionally, there are two or three nodules, and in some instances there are numerous or even innumerable nodules. Most patients are children, but in some patients, a nodule is present already at birth or does not appear until about adult life; in some instances, the surface of the nodule is verrucous, but it may be smooth. The most common location of the nodule is the face. A 12‐year‐old Yemeni child patient presented with warty, hard‐ and smooth‐surface, white, and small and large non‐itchy numerous nodules in the face and in the four extremities, which started at 4 years after birth, of 8 years' duration. Serum levels of calcium, phosphorous, and parathyroid hormones were normal. Plain chest X‐ray, abdominal ultrasonography, and complete blood count picture were normal. Skin biopsy followed by histopathological examination was diagnostic. The patient was treated with curettage and surgical removal.     

Cutaneous Plexiform Schwannomas in a Patient with Neurofibromatosis Type 2

Plexiform schwannoma is a rare benign neoplasm of the neural sheath characterized by a multinodular plexiform growth pattern. The tumor usually occurs as an isolated finding, although rare cases have been reported in association with neurofibromatosis type 2 (NF2). A 25-year-old man was admitted for foot drop. He had an asymptomatic skin-colored nodule on his neck that had been present for 10 years. His medical history included local excision of a plexiform schwannoma on his left leg in our dermatology clinic 6 years prior. A histopathological examination of the skin-colored nodule also showed the typical microscopic features of a plexiform schwannoma, including the characteristic Antoni type A areas showing frequent nuclear palisading and Verocay bodies. Magnetic resonance imaging revealed a meningioma and a vestibular schwannoma in the cranium and multiple neurofibromas on the spinal cord. Herein we report a rare case of cutaneous plexiform schwannomas in a patient with NF2.     

A Case of Eccrine Spiradenoma in a Patient with Neurofibromatosis

Neurofibromatosis is a systemic hereditary disorder with varied manifestations in bone, soft tissue, the nervous system and skin. Cutaneous manifestations of neurofibromatosis are characterized by café-au-lait macules, multiple neurofibromas, Lisch nodules and intertriginous freckling. Some benign or malignant tumors such as juvenile xanthogranuloma, pheochromocytoma, and malignant melanoma can accompany neurofibromatosis. But, in the English literature, no case of eccrine spiradenoma associated with neurofibromatosis has been reported. Eccrine spiradenoma is a benign uncommon neoplasm of skin adnexa. It presents as a painful, slow-growing and solitary nodule on the head or upper trunk. Here, we report a rare case of eccrine spiradenoma in a patient with neurofibromatosis.     

Poroid Hidradenoma: A Two-Case Report and Literature Review

Poroid hidradenoma (PH) is a rare benign tumor that shows differentiation of the eccrine sweat gland. It occurs mainly in adults, presenting as a 0.5 to 2 cm-sized intradermal nodule, mostly on the head, extremities, trunk and neck. We report two rare cases of PH, one on the face and the other on the heel. The first patient was a 50-year-old male who had a solitary, skin-colored nodule on his right temple for 6 months. The second patient was a 67-year-old female who presented with a solitary, bean-sized, tender nodule on her left heel for 1 year. The common histological examination finding was a well-circumscribed tumor composed of solid portions and large cystic spaces in the center. The tumor cells consisted of small, monomorphic poroid cells and large cuticular cells in both cases. To our knowledge, only few cases of PH have been reported. Herein, we report two rare cases of PHs with literature review.     

Uncommon Presentation of a Common Histiocytic Tumor: A Rare Entity

Juvenile xanthogranuloma (JXG) is the most common form of non-Langerhans cell histiocytic lesion, characterized by benign, usually asymptomatic, self-healing yellowish brown papulonodular lesions of skin and other organs in the absence of metabolic disorder. The cells of origin of JXG are dermal dendrocytic cells. Histopathologically there is dermal infiltration of foamy or non-foamy histiocytes with or without giant cell. Immunohistochemistry shows CD68 positivity with CD1a and S-100 negativity of lesional cells although S-100-positive JXG have been reported. JXG may be associated with neurofibromatosis type one (NF 1) with increased risk of juvenile chronic myelogenous leukemia and other hematological malignancies. Our case was S-100 immunoreactive multiple, cutaneous JXGs with NF 1 without any visceral involvement or malignant complication. We are presenting this case due to its rarity.     

Confused subcutaneous nodules in children: Differential diagnosis of pilomatricoma in children

Background

Pilomatricoma is a common but easily misdiagnosed tumor in children.

Aims

To differentiate pilomatricoma from other common subcutaneous nodules in children.

Patients/Methods

Misdiagnosed subcutaneous nodules in four children were recorded.

Results

A red mass on a 7-year-old boy's head which had been misdiagnosed pyogenic granuloma was proved to be pilomatricoma. A red mass on an 8-month-old boy's face which had been misdiagnosed infantile hemangioma also turned to be pilomotricoma. A red mass on a 21-month-old girl's breast, which had been misdiagnosed pilomatricoma, was proved to be infantile myofibroma. A subcutaneous nodule under a 13-month-old girl's armpit, which had been misdiagnosed pilomatricoma, turned to be BCG-associated lymphadenitis.

Conclusions

When a child with a subcutaneous nodule attends, pilomatricoma, vascular tumors, fibrous tumors, and BCG-associated lymphadenitis should be considered.