Localized unilateral basaloid follicular hamartoma along Blaschko's lines on face.

Basaloid follicular hamartoma (BFH) is a rare hamartoma of hair follicle. Clinical presentations may vary but are united by the same histopathological features in the form of folliculocentric basaloid or squamoid cell proliferation in the superficial dermis, which represents malformed and distorted hair follicles. It is important to recognize this entity as its simulant is basal cell carcinoma, a low-grade malignancy. Here, we report a case of localized unilateral BFH in a Blaschkoid distribution on the face of a 14-year-old female.

Pápulas múltiples con distribución unilateral y segmentaria en mujer de 65 años / A 65-Year-Old Woman With Multiple Papules in a Unilateral Segmental Distribution

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Histologic Mimics of Basal Cell Carcinoma.

CONTEXT: - Basal cell carcinoma (BCC) is the most common human malignant neoplasm and is a frequently encountered diagnosis in dermatopathology. Although BCC may be locally destructive, it rarely metastasizes. Many diagnostic entities display morphologic and immunophenotypic overlap with BCC, including nonneoplastic processes, such as follicular induction over dermatofibroma; benign follicular tumors, such as trichoblastoma, trichoepithelioma, or basaloid follicular hamartoma; and malignant tumors, such as sebaceous carcinoma or Merkel cell carcinoma. Thus, misdiagnosis has significant potential to result in overtreatment or undertreatment. OBJECTIVE: - To review key features distinguishing BCC from histologic mimics, including current evidence regarding immunohistochemical markers useful for that distinction. DATA SOURCES: - Review of pertinent literature on BCC immunohistochemistry and differential diagnosis. CONCLUSIONS: - In most cases, BCC can be reliably diagnosed by histopathologic features. Immunohistochemistry may provide useful ancillary data in certain cases. Awareness of potential mimics is critical to avoid misdiagnosis and resulting inappropriate management.

T-Helper Type 9 Cells Play a Central Role in the Pathogenesis of Respiratory Epithelial Adenomatoid Hamartoma.

The etiology and pathogenesis of respiratory epithelial adenomatoid hamartoma (REAH) remain poorly understood, although some reports have suggested that REAH features an inflammatory process. T-helper type 9 (Th9) cells are a newly identified subset of CD4 T-helper cells characterized by the expression of high levels of interleukin (IL)-9, which may promote inflammation. As REAH may involve an inflammatory process, we evaluated whether IL-9 and/or Th9 cells were present in REAH and compared the levels thereof to those of normal nasal mucosa. Eleven patients with REAH and 5 exhibiting cerebrospinal fluid leakage were included in the study. Flow cytometry was used to measure Th9 cell numbers, a cytometric bead assay was applied to measure IL-9 levels, and real-time polymerase chain reaction was used to quantify the levels of mRNA encoding IL-9. Th9 cells, IL-9 mRNA, and IL-9 were detected in all REAH and control samples. The proportion of Th9 cells in the patients with REAH was significantly greater than that in the controls. The expression levels of IL-9-encoding mRNA and IL-9 protein were significantly higher in the patients with REAH than in the controls. The Th9 cell subset was expanded, the synthesis of IL-9-encoding mRNA was upregulated, and IL-9 secretion was increased in REAH tissue, suggesting that Th9 cells play a central role in the pathogenesis of the disease.

Eruptive vellus hair cysts: report of a new case with immunohistochemical study and literature review.

Eruptive vellus hair cysts (EVHC) are rather uncommon lesions, of which 222 cases have been published in the literature. Their etiopathogenesis is poorly known. We report herein a new typical case of EVHC that was studied immunohistochemically. A 15-year-old male presented with a 4-year history of progressively developing small brown-gray papules on the trunk and extremities. Microscopically the lesions consisted of small epidermoid cysts containing vellus hairs. Immunohistochemically, the lesions expressed keratin 1/10, calretinin and p63 but no epithelial membrane antigen, filaggrin or androgen receptors. A review of the relevant literature shows that EVHC may be inherited or acquired and may be associated to other genodermatoses, namely sebocystomatosis. They could be due to hamartomatous follicular growth, to a trouble in infundibular keratinization leading to vellus hair follicle occlusion, or represent an example of acquired hamartoma. Although benign, this condition is difficult to treat.

Hypocellular medallion-like dermal dendrocyte hamartoma (plaque-like CD34-positive dermal fibroma).

Medallion-like dermal dendrocyte hamartoma (MLDDH) is a recently described congenital dermal neoplasm. Only 11 cases have been reported in the English literature and therefore its clinical and pathological manifestations are not completely defined. We report the case of a 20-year-old male presenting with a round, erythematous, atrophic plaque on the midline of the anterior aspect of the neck. The lesion was asymptomatic and was stable since birth. A skin biopsy was performed. Histological examination showed a band like hypocellular fibrotic area in the superficial reticular dermis, which did not spread to subcutaneous tissue. The cells were CD34-positive and S100 and CD56-negative. Elastic fibers were present. Altogether the morphological and immunostaining features were neither suggestive of dermatofibrosarcoma protuberans nor neurofibroma. Thus, the pathological findings were consistent with MLDDH. Clinical differential diagnosis includes anetoderma, aplasia cutis, or atrophic DFSP. Histological differential was made with atrophic scar and striae distensae. Although the histological findings were not identical to those described recently as characteristic, the clinical features were suggestive enough to make the diagnosis of MLDDH. Therefore in our experience, the MLDDH spectrum might include lesions with variable cellular density, which can show similar clinical manifestations.

Cowden's syndrome: a clinical, immunological, and histopathological study.

BACKGROUND: Cowden's syndrome is a rare, autosomal dominant condition characterized by hamartomas of the gastrointestinal tract and cancer of the breast and thyroid. This study describes the clinical, immunological, and histopathological status of four Cowden's syndrome cases from two different families. METHODS: Biopsies were taken from different skin, mucous membrane, and intestinal lesions in all patients. Blood samples from patients and their parents were also examined. RESULTS: Two brothers in the first family had more flexural distribution of papular and warty skin lesions as well as other manifestations of the syndrome, including recurrent pyogenic and fungal infections. Flow cytometric study revealed decreased total T and B-cell percentages and abnormal helper: suppressor ratios in these patients. The other two patients from the second family showed the classical picture of the syndrome and normal immunological parameters. Histopathologically, most skin lesions of the face showed trichilemmomas, and all oral and some of the other skin lesions showed benign fibromas with giant cells (Cowden's fibroma). Examination of intestinal biopsies revealed hamartomatous and hyperplastic polyps. CONCLUSIONS: Some cases of Cowden's syndrome may be associated with prominent flexural skin lesions, recurrent pyogenic and fungal skin infections, decreased total T and B-cell counts, and an abnormal helper:suppressor ratio.

Chorioangiomas--new insights into a well-known problem. II. An immuno-histochemical investigation of 136 cases.

AIMS: Chorioangiomas are benign tumors of the hemochorial placenta. They are malformations or hamartomas, formed as a result of defective angiogenesis. They are of clinical importance due to their association with premature placental release and pre-eclampsia. METHODS: Since a link has been established in neoplasias between tumor growth and an increased expression of angiogenic growth factors, 136 samples of chorioangiomas and 136 samples of tumor-free placental tissue were examined in terms of proliferation rate and expression of the growth factors angiopoietin-1 and -2, the angiopoietin-receptor Tie-2, PDGF and the PDFG beta-receptor. RESULTS: The chorioangiomas exhibited differing proliferation rates, whereas tumor-free placental tissue barely proliferated at all. Angiopoietin expression was--morphologically--considerably higher within the chorioangiomas than in the comparison placentas; morphological amounts of the Tie-2 receptor were identical in all samples. Expression of PDGF and its receptor was the same for chorioangiomas and tumor-free placentas. CONCLUSIONS: According to this study and the current literature in the field of hamartomas and some neoplasia, we can assume that increased growth factor expression plays a role in the formation of chorioangiomas, since it stimulates proliferation in a wide variety of cell compartments.

Basaloid/follicular hyperplasia overlying connective tissue/mesenchymal hamartomas simulating basal cell carcinomas.

BACKGROUND: Basaloid hyperplasia has been described overlying dermatofibromas as well as in the epidermis overlying nevus sebaceus. Although the morphology of these areas may resemble that of basal cell carcinoma (BCC), in the majority of cases aggressive behavior of the proliferation is not seen. In fact, the basaloid proliferation often shows follicular differentiation and may be stimulated and maintained by its relationship with the underlying stromal cells. OBJECTIVE: We wanted to determine whether immunohistochemical staining for antibodies, which may suggest differences in pathogenesis, were different in basaloid hyperplasia overlying connective tissue/mesenchymal hamartomas and BCC. METHODS: We report 3 cases of connective tissue/mesenchymal hamartomas with overlying basaloid hyperplasia, in which the areas of the basaloid proliferation showed follicular differentiation. Immunohistochemical stains included Ber-EP4, PCNA, Ki-67, Bcl-2, p53, SM-Actin, CD31, factor XIIIa, KP-1, and CD34. RESULTS: There was a diffuse positive reaction for Ber-EP4 in all specimens and there was increased nuclear staining for PCNA and Ki-67. There was focal cytoplasmic staining for Bcl-2 in the areas of basaloid hyperplasia. Immunohistochemical staining for p53 showed only scattered positive cells except in a small focus in the areas of basaloid hyperplasia. The connective tissue component of all lesions showed diffuse staining for CD34 surrounding areas of basaloid hyperplasia in the mesenchymal component as well as in abundant S-100(+) nerves. CONCLUSION: The areas of basaloid hyperplasia in these hamartomas exhibited an immature phenotype similar to that seen in both BCCs and follicular tumors; however, the patterns of proliferation markers, p53, Bcl-2, and the surrounding stromal cell markers were similar to those of benign follicular tumors. Thus the staining pattern for this group of antibodies suggests that areas of basaloid hyperplasia are not BCC.

Loss of cutaneous delayed hypersensitivity reactions in nevus anemicus. Evidence for close concordance of cutaneous delayed hypersensitivity and endothelial E-selectin expression.

BACKGROUND: The relationship of adhesion molecules in the dermis to immunologically mediated cutaneous inflammation can be understood by focusing on a serendipitous phenomenon: a lack of dermatitis within the margins of a nevus anemicus (NA) in generalized contact dermatitis. The expression and induction of endothelial and epithelial adhesion molecules with intradermally injected cytokines were investigated. OBSERVATIONS: Nevus anemicus without dermatitis lacked histopathological changes consistent with inflammatory cellular infiltration. The surrounding skin of the dermatitic lesion expressed HLA-DR, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule 1, and E-selectin on endothelial cells, and HLA-DR and ICAM-1 in the epidermis. However, the skin of the NA lacked endothelial E-selectin and epidermal HLA-DR and ICAM-1 expression. Interferon gamma, injected intradermally, induced endothelial and epidermal HLA-DR and ICAM-1 expression in the NA and surrounding normal skin. While interferon gamma strongly induced E-selectin expression on endothelial cells in normal skin, it failed to induce endothelial E-selectin expression in the NA. CONCLUSIONS: This study suggests that vessels in the NA do not respond normally to proinflammatory cytokines, at least at the level of E-selectin expression. The absence of keratinocyte ICAM-1 and HLA-DR expression in the NA lesion in contact dermatitis is likely caused by the absence of infiltrating lymphocytes, rather than by the intrinsic unresponsiveness of keratinocytes to interferon gamma. Among the endothelial cell adhesion molecules in delayed hypersensitivity, E-selectin appears to be indispensable in recruiting circulating T lymphocytes to the skin.

The so-called bile duct adenoma is a peribiliary gland hamartoma.

The cell phenotype of so-called bile duct adenoma (BDA) was investigated immunohistochemically using monoclonal antibodies to two recently identified antigens (designated D10 and 1F6) extracted from human liver and cultured biliary epithelium. The acini and tubules of BDA consisted of serous and mucous cells that expressed D10 and 1F6. The intrahepatic peribiliary glands of normal liver, comprising intramural mucous glands and extramural tubuloalveolar seromucinous glands, similarly expressed D10 and 1F6 antigens. Antigen 1F6 was present in the cells forming the canals of Hering and normal bile ductules but not in interlobular and larger bile ducts. Proliferating bile ductules associated with large bile duct obstruction and alcoholic cirrhosis or the epithelia of the von Meyenberg complex and polycystic liver did not exhibit this combined profile of D10 and 1F6 expression and mucous cells. These findings suggest an origin of BDA from peribiliary glands rather than from bile ductules or ducts. Consistent with this view was our finding that 18 of the 30 BDA were spatially related to a large-calibre bile duct. Therefore, BDA, well known for its benign behavior is a small mass of disorganized but mature peribiliary gland acini and tubules within a variable amount of stroma and should properly be called a peribiliary gland hamartoma.

Immunohistochemistry of port-wine stains and normal skin with endothelium-specific antibodies PAL-E, anti-ICAM-1, anti-ELAM-1, and anti-factor VIIIrAg.

BACKGROUND AND DESIGN: Immunohistochemical analysis using four monoclonal antibodies specific for endothelium was performed to evaluate the possible role the endothelium may play in the pathogenesis of port-wine stains. In 11 patients with port-wine stains, biopsy specimens were obtained from involved and normal skin. On frozen tissue sections, we studied and compared the distribution and staining pattern of PAL-E, anti-intercellular adhesion molecule-1 (ICAM-1), anti-endothelial leukocyte adhesion molecule-1 (ELAM-1), and anti-factor VIIIrAg (FVIIIrAg), all recognizing specific epitopes of vascular endothelial cells. RESULTS: The PAL-E, anti-FVIIIrAg, and anti-ICAM-1 antibodies showed a similar distribution and staining pattern. The intensity of staining was equally strong with PAL-E and FVIIIrAg, while the expression of ICAM-1 was moderate. The ELAM-1 antibody exhibited only a weak expression in about 70% of evaluated specimens. No substantial differences in the intensity and distribution pattern of expression of these proteins could be demonstrated between normal skin and port-wine stains. CONCLUSION: Our findings suggest that the abnormal vessel pathologic findings in port-wine stains are not due to defects associated with the endothelium. According to PAL-E antibody staining properties, port-wine stain vessels could be classified as capillaries and/or postcapillary venules and small veins.

Inflammatory linear verrucous epidermal naevus with auto-immune thyroiditis: coexistence of two auto-immune epithelial inflammations?

We report a patient with an inflammatory linear verrucous epidermal naevus (ILVEN) coexisting with an auto-immune lymphocytic thyroiditis. The occurrence of two epithelial inflammatory processes could be linked and raises the question of auto-immune involvement in the inflammatory part of ILVEN. Moreover, expression of a membrane antigen, OKM5, usually assigned to antigen-presenting cells, especially macrophages, has been demonstrated on keratinocytes in some dermatological diseases including ILVEN. These data suggest that keratinocytes in ILVEN could present some antigens and perhaps auto-antigens modified by the hamartomatous process, leading to an (auto-immune?) inflammatory reaction.

Giant hamartoma of the lung with a high production of carbohydrate antigen 19-9.

A rare case of a giant pulmonary hamartoma with a high production of carbohydrate antigen (CA) 19-9 is presented. A 43-year-old woman with complaints of cough, fever, and chest pain was diagnosed as having a posterior mediastinal tumor with pneumonia. The serum CA 19-9 level was high. A thoracotomy revealed an intrapulmonary solid mass with a histologic diagnosis of cartilaginous hamartoma with no evidence of malignancy. The CA 19-9 concentration in the mucus of the tumor was high, and postoperatively the serum CA 19-9 level returned to normal. The CA 19-9 could be immunohistochemically demonstrated on the surface of the tumor.

Melanoma-associated antigens in tumours of the nervous system: an immunohistochemical study with the monoclonal antibody HMB-45.

The aim of this study was to determine the specificity and sensitivity of the commercially available, monoclonal anti-melanoma antibody HMB-45 in brain tumours and peripheral nerve sheath tumours. Hence, a series of 155 different non-melanotic tumours of the central and peripheral nervous system were examined immunohistochemically. The brain lesions consisted of primary tumours and metastases from various carcinomas. Twenty melanotic tumours (cerebral metastases of malignant melanomas, meningeal melanomatosis, meningeal melanocytomas) and dermal blue cell naevi served as controls. All melanotic tumours stained positive. Furthermore, a positive immunohistochemical reaction was observed in the following non-melanotic tumours: gliosarcomas, primitive neuroectodermal tumours, ependymoma, malignant schwannomas and different intracranial hamartomas. Two plasmacytomas and 4 metastatic carcinomas also revealed positive staining for HMB-45. Our results confirm the necessity for cautious interpretation of HMB-45 immunoreactivity as a tool in the immunohistochemical characterization of nervous system tumours.

Splenic hamartoma and capillary hemangioma are distinct entities: immunohistochemical analysis of CD8 expression by endothelial cells.

The histologic and immunohistologic features of two morphologically similar splenic tumors, a capillary hemangioma and a splenic hamartoma, are reported. The hemangioma was composed predominantly of small vascular channels lined by endothelium expressing factor VIII-related antigen and lacking T-subset antigen (CD8). In contrast, the splenic hamartoma was predominantly a spindle cell lesion with numerous vascular channels coursing through the tumor; these contained splenic-type endothelium expressing both CD8 and factor VIII-related antigen. Our results justify the concept that the splenic hamartoma is a tumor of splenic origin or a true hamartoma and is distinct from the splenic capillary hemangioma.

Immunofluorescence and electron microscopic findings in a congenital arrector pili hamartoma.

A congenital arrector pili hamartoma is a neoplasm that presents as multiple or solitary dermal nodules in a dermatomal distribution. To elucidate and clarify its histogenesis, a lesion derived from a 3-year-old boy was studied by light microscopy, indirect immunofluorescence, using antibodies against basal lamina constituents and against interstitial matrix components, and electron microscopy. In addition, a rabbit antibody specific for bovine smooth-muscle myosin was used. The antibodies against the basal lamina components and fibronectin all showed an intense perimysial fluorescence that ensheathed and surrounded individual leiomyocytes. Anti-smooth-muscle myosin exhibited intense cytoplasmic fluorescence. Furthermore, electron microscopy showed fusiform cells with abundant myofilaments, dense bodies, and pericellular basal lamina as seen in smooth muscle. These studies suggest the probable origin of this hamartoma from pili arrector muscle and could be used as an adjunct in histopathological diagnosis.