Blue rubber bleb nevus syndrome and pulmonary hypertension: an unusual association

INTRODUCTION: Blue rubber bleb nevus syndrome (BRBNS) is a rare congenital systemic angiodysplasia with multiple vascular malformations in the skin, gastrointestinal tract and, less often, in other internal organs and the brain. CASE REPORT: A 36-year-old man with past history of BRBNS was admitted to our hospital for progressive dyspnea and fatigue. Primary pulmonary hypertension (PPH) was diagnosed. He then developed acute abdominal pain and dyspnea, dying in a few hours due to sudden cardiac arrest. Postmortem examination demonstrated angiomatous lesions located in the skin, small bowel, heart, lungs, liver and thyroid. The lesions were slightly raised, soft and compressible and microscopically consisted of dilated vascular channels lined by a flattened endothelium. The vascular wall was formed by several layers of smooth muscle cells, intermixed with abundant aggregates of elastic lamellae and thin collagen fibers. Luminal thrombi were a frequent finding. In the small bowel, we identified the presence of an abnormally large artery directly opening into a thin-walled venous channel. The most striking finding in the lungs was the presence of thrombi of varying age in the lumen of segmental and elastic arteries, as well as muscular arteries and arterioles. Severe medial hypertrophy of muscular arteries and muscolarization of arterioles were also present. Intimal proliferative lesions and plexiform lesions were never observed. CONCLUSION: The pulmonary findings are consistent with recurrent thromboembolic events from shunts in the visceral lesions. To our knowledge, this is the first report of BRBNS with visceral arterovenous (AV) fistulae complicated by thromboembolic pulmonary hypertension (PH).     

Balloon cell nevus of the soft palate: an immunohistochemical and ultrastructural study

An ultrastructural analysis of oral balloon cell nevus of intramucosal type complemented with an immunohistochemical study was performed for the first time. The lesion was composed of large balloon cells with an admixture of small nevus cells and melanophages at the periphery. Balloon cells showed cytoplasmic accumulation of vacuoles of varying sizes and the presence of microgranular and vacuolated melanosomes were found. Residual cytoplasm contained no identifiable organelles. A spectrum of transitional forms between balloon cells and conventional nevus cells with microvacuoles was readily observed. Both cells exhibited intense immunoreactivity to multiple melanocytic markers. Ballooning phenomenon was not evident in melanophages containing a large amount of melanosome complex. It can be inferred, from the present and previous observations, that progressive vacuolization of melanosomes in nevomelanocytes may be responsible for the formation of peculiar ballooning appearance, suggesting an aberrant melanogenesis.     

Stromal Melanocytic Foci ("Blue Nevus") in Step Sections of the Uterine Cervix

Stromal melanocytic foci (SMF) of the uterine cervix, which are known as extracutaneous blue nevus, were examined in step sections of the cervix. A total of 189 uterine specimens surgically excised for leiomyoma, adenomyosis etc., were studied. The over-all incidence of SMF of the cervix was 28.6% (54/189 cases). The incidence of these lesions increased with age, and they were most prevalent in the sixth decade of life (12/30 cases, 40%). SMF were presented more often in the anterior wall than in the posterior wall. Most of the lesions were less than 1 mm in size. No case of SMF demonstrated expansive tumorous growth. Six of 54 cases of SMF displayed consecutive spread of SMF in almost all step sections of the cervix. The histological findings confirmed that SMF of the cervix is quite common existence among Japanese women. It is speculated that the mucosal region near the skin and/or cutaneus region near the mucosa may have stromal melanocytosis; malignant melanoma could develop from SMF of the cervix, which did not have junctional activity because of stromal melanocytic origin. Acta Pathol Jpn 41: 751-756, 1991.     

Blue nevus of the prostate

Blue nevus is one of the melanotic lesions that can incidentally arise in the prostate gland. A literature review identified 28 previously reported cases, and although rare, the blue nevus appeared to be the commonest melanocytic lesion arising in the prostate. The differential diagnosis includes melanosis and malignant melanoma, as well as nonmelanotic lesions due to deposition of lipofuscin, hemosiderin and, rarely, homogentisic acid. The distinction among these lesions can typically be made based on morphologic grounds but may also be aided by histochemical and immunohistochemical stains such as stains for iron, S100 protein, HMB-45, and CD68 as needed. Blue nevus of the prostate is a benign lesion with no malignant potential to date, so no further treatment is warranted.     

Balloon cell nevus of the iris

Balloon cell nevus is a rare histopathological lesion characterized by a predominance of large, vesicular and clear cells, called balloon cells. There is only 1 case of balloon cell nevus of the iris reported in the literature.Case reportA 55 year-old man presented a pigmented elevated lesion in the right iris since the age of 12 years old. The lesion had been growing for the past 2 years and excision was performed. Histopathological examination showed a balloon cell nevus composed of clear and vacuolated cells without atypia. A typical spindle cell nevus of the iris was also observed. The differential diagnosis included xanthomatous lesions, brown adipocyte or other adipocytic lesions, clear cell hidradenoma, metastatic clear cell carcinoma of the kidney and clear cell sarcoma. The tumor was positive for Melan A, S100 protein and HMB45.ConclusionBalloon cell nevus of the iris is rare but should be considered in the differential diagnosis of melanocytic lesions of the iris.     

Blue nevus of the uterine cervix

The clinical, gross pathologic, and light and electron microscopic features of three blue nevi of the endocervix were studied. Immunocytochemical studies for the localization of S-100 protein in the blue nevus cells were performed. A comprehensive review of 47 previously published cases is also presented. Blue nevi of the endocervix appear to be rare incidental lesions; they are often found in hysterectomy specimens from middle-aged women. The lesion is seldom detected clinically or colposcopically. However, it appears in most instances as a blue-black lesion in the posterior wall of the endocervix on gross pathologic examination. The demonstration of S-100 protein in the blue nevus cells before and after bleaching in the present study, along with the ultrastructural observations, supports combined melanocytic and schwannian differentiation of the blue nevus cell.     

HRAS-related epidermal nevus syndromes: Expansion of the spectrum with first branchial arch defects

Epidermal nevus syndrome (ENS) comprises a heterogeneous group of neurocutaneous syndromes associated with the presence of epidermal nevi and variable extracutaneous manifestations. Postzygotic activating HRAS pathogenic variants were previously identified in nevus sebaceous (NS), keratinocytic epidermal nevus (KEN), and different ENS, including Schimmelpenning–Feuerstein–Mims and cutaneous-skeletal-hypophosphatasia syndrome (CSHS). Skeletal involvement in HRAS-related ENS ranges from localized bone dysplasia in association with KEN to fractures and limb deformities in CSHS. We describe the first association of HRAS-related ENS and auricular atresia, thereby expanding the disease spectrum with first branchial arch defects if affected by the mosaic variant. In addition, this report illustrates the first concurrent presence of verrucous EN, NS, and nevus comedonicus (NC), indicating the possibility of mosaic HRAS variation as an underlying cause of NC. Overall, this report extends the pleiotropy of conditions associated with mosaic pathogenic variants in HRAS affecting ectodermal and mesodermal progenitor cells.     

Malignant melanoma arising in a plaque‐type blue nevus

Blue nevus is a type of dermal melanocytosis and has a variety of clinicopathological characteristics. A few particular variants are generally accepted as discrete clinicopathological entities. Plaque‐type blue nevus (PTBN) is one of the variants of blue nevus. PTBN presents at birth or arises in early childhood, and shows a combination of features found in common blue nevus and cellular blue nevus. In this report, we describe a malignant melanoma arising in association with a PTBN in a 65‐year‐old male. The tumor appeared as a well circumscribed but partially infiltrative upper‐abdominal mass, and was heavily pigmented and consisted of a spindle or epithelioid highly cellular component with mitotic figures and tumor necroses. In the skin around the tumor, multiple pigmented lesions were scattered around the trunk, and these had been recognized since childhood. Histologically, skin lesions showed sparse and wide distribution of the dendritic melanocytes with dense melanin pigments and melanophages between the collagen bundles from the reticular dermis to the abdominal skeletal muscle. We also discuss the histological features and clinical course in our patient in context with previous related literature.     

Apoptosis in abortive hair follicular components in the organoid nevus

A previously undescribed fact that a small number of apoptotic bodies are present in about 62% of abortive hair follicles of the organoid nevus is discovered. The immaturity and frequency of apoptosis in the hair follicles seemed to be closely related to the hairless condition of the organoid nevus.     

Histopathologic study of the rectum in 1,464 consecutive rectal specimens in a single Japanese hospital: II. malignant lesions

The author investigated histopathology of 1,464 consecutive rectal specimens in of our pathology laboratory in Japan. A review of pathological reports was done by computer. Observation of histological slides was performed, when appropriate. The rectal specimens were composed of 1,041 benign lesions and 423 malignant lesions. The 423 malignant lesions were composed of 367 cases of primary rectal carcinoma, 41 cases of carcinoma in adenoma, 7 cases of neuroendocrine tumor, 3 cases of malignant lymphoma, 2 cases of gastrointestinal stromal tumors (GIST), and 3 cases of metastatic carcinoma. Of the 367 cases of primary rectal carcinoma, 37 cases were early carcinomas whose invasion was limited up to the submucosa (early rectal carcinoma). The remaining 330 cases were advanced carcinoma invading beyond the proper muscle layer. The histological types were well differentiated adenocarcinoma in 197 cases, moderately differentiated adenocarcinoma in 129 cases, poorly differentiated adenocarcinoma in 10 cases, mucinous adenocarcinoma in 24 cases, signet ring cell carcinoma in 6 cases, squamous cell carcinoma in 1 case In the 41 cases of carcinoma in adenoma, the carcinoma was well to moderately differentiated adenocarcinoma, and all cases were early carcinomas without invasion or with little invasions to subserosa. The size of carcinoma in adenoma was as follows: < 10 mm, 5 cases; 10-15 mm, 8 cases; 15-20 mm, 23 cases; > 20mm, 5 cases. The background adenoma was as follows: tubular adenoma (n=15), tubulo-villous adenoma (n=14), and villous adenoma (n=12). The 7 cases of neuroendocrine carcinoma consisted of 6 low grade neuroendocrine tumors (carcinoids) and 1 high grade neuroendocrine carcinoma (small cell carcinoma). All were submucosal lesions. Immunohistochemically, the tumor cells were positive for two or more of synaptophysin, chromogranin, neuron-specific enolase, CD56. In small cell carcinoma, KIT and PDGFRA were consistently positive. The 3 cases of malignant lymphoma were diffuse large B-cell lymphomas positive for CD20 and CD79a and negative for NK/T cell markers. The two cases of GIST was spindle cell type, and the risk was intermediate. Kit mutations were recognized in both GISTs. No PDGFRA mutations were seen. Of the 3 metastatic carcinomas, one was a metastasis from prostatic adenocarcinoma, and the remaining two was adenocarcinoma of unknown primary sites.     

Familial systematized epidermal nevus syndrome

Epidermal nevi are typically congenital but rarely familial. We report on a family in which 3 relatives have systematized epidermal nevi. The propositus also has evidence of a hemangioma and a hemangioendothelioma. Peripheral blood and skin fibroblast karyotypes of the propositus did not show evidence of mosaicism. Epidermal nevi have been associated with nondermatologic pathology, involving the nervous, vascular, and skeletal systems in sporadic cases. This report demonstrates that nondermatologic pathology can be also be associated with systematized epidermal nevi in a familial setting. The apparent skipping of generations may be explained by autosomal dominant inheritance with decreased penetrance. © 1992 Wiley-Liss, Inc.     

Compound melanocytic nevus arising in a mature cystic teratoma of the ovary

A 28-year-old woman complained of irregular menstruation. Abdominal ultrasound and magnetic resonance imaging (MRI) examinations revealed a cystic tumor in the left ovary. A histological examination of the resected ovary revealed that the lesion was a mature cystic teratoma. In this tumor, components such as skin with appendages, a thyroid gland, mucosa of the digestive tract and a submandibular gland were observed. Interestingly, compound melanocytic nevus was also present in the skin component. To the best of our knowledge, this is the sixth reported case of nevus arising in a mature cystic teratoma of the ovary. Despite the extreme rarity of such a lesion, pathologists should recognize the possibility of such lesions occurring in ovarian teratoma.     

Blue nevus of the uterine cervix.

A case of blue naevus of the endocervix is reported with immunohistochemical and ultrastructural findings. The dendritic melanin-containing cells are analogous to the blue naevi cells of the skin. Electron microscopy showed melanosomes in dendritic cells but no cells with melanin-producing Schwann cells features were observed. Histogenetic hypotheses are discussed.     

巨痣的整形外科治疗进展

【摘要】为探讨治疗巨痣较为有效的手术方式,通过查阅CNKI、万方、PubMed等数据库中巨痣治疗相关文献,分析巨痣治疗不同手术方式适应证及利弊等,筛选较为合理的手术方式。结果显示巨痣手术方式较多,适应证及优缺点各异,综合治疗水平在不断进步。因此巨痣术前设计应个体化、综合性考虑,选择适宜的手术方式。     

Further delineation of the phenotypic spectrum of nevus comedonicus syndrome to include congenital pulmonary airway malformation of the lung and aneurysm

Nevus comedonicus syndrome (NCS) is a rare epidermal nevus syndrome characterized by ocular, skeletal, and central nervous system anomalies. We present a 23‐month‐old boy with a history of a congenital pulmonary airway malformation (CPAM) of the lung and a congenital cataract who developed progressive linear and curvilinear plaques of dilated follicular openings with keratin plugs (comedones) on parts of his scalp, face, and body consistent with nevus comedonicus. MRI of the brain demonstrated an aneurysm of the right internal carotid artery. Genetic testing identified NEK9 c.1755_1757del (p.Thr586del) at mean allele frequency of 28% in the nevus comedonicus. This same mutation was present in the CPAM tissue. This is the first case of a CPAM in a patient with an epidermal nevus syndrome. This case expands the phenotype of nevus comedonicus syndrome to include CPAM and vascular anomalies.