Eccrine angiokeratomatous hamartoma combined with solitary angiokeratoma or verrucous venous malformation: Report of two cases and comprehensive review of the literature.

First reported in 2006, eccrine angiokeratomatous hamartoma is a very rare vascular malformation of the skin, with only few described cases. It has a peculiar histopathology with features deriving from the combination of two different vascular malformations of the skin: solitary angiokeratoma and eccrine angiomatous hamartoma. In the past, other authors described similar hamartomatous lesions with features deriving from verrucous venous malformation and eccrine angiomatous hamartoma. We believe that these lesions are clearly overlapping from clinical, histopathological, and immunohistochemical points of view and the term "eccrine angiokeratomatous hamartoma" should be used to indicate the whole spectrum of these lesions as suggested by Kanitakis et al. Herein we present two cases of this rare vascular hamartoma, with clinical, histopathological and immunohistochemical characterization. In addition, for the first time we report a complete and detailed review of the literature to clarify the clinical, epidemiological, and histopathological features of this unique entity.

Ghrelin-producing well-differentiated neuroendocrine tumor (carcinoid) of tailgut cyst. Morphological, immunohistochemical, ultrastructural, and RT-PCR study of a case and review of the literature.

Well-differentiated neuroendocrine tumors (carcinoids) arising in the presacral space are rare neoplasms that can arise in association with either sacrococcygeal teratomas or tailgut cysts. Although tumors arising in tailgut cysts are more frequent than those associated with teratomas, they are still very rare, and only 13 cases have been reported in the literature. We describe the first case of a carcinoid composed of ghrelin-producing cells arising in a tailgut cyst. Ghrelin production was demonstrated using immunohistochemistry, electron microscopy, and reverse transcription-polymerase chain reaction methods. A 73-year-old woman with back and pelvic pain was found to have a presacral mass histologically diagnosed, on needle biopsy, as a well-differentiated neuroendocrine tumor. Workup did not show another primary tumor or metastatic disease. The patient underwent laparoscopic resection of the mass, and the pathological diagnosis of the surgical specimen was of a tailgut cyst-associated carcinoid composed of ghrelin-producing cells. In addition, we have accurately reviewed the literature on presacral carcinoids, associated or unassociated with tailgut cysts, to give the reader a comprehensive overview of these very rare tumor types.

Mesenchymal hamartoma of the liver: A proliferative lesion of possible hepatic stellate cell (Ito cell) origin.

An asymptomatic 17-month-old male infant was incidentally found to have a hepatic mass measuring 12cm in maximum dimension. The histopathologic appearance of the resected mass was that of a typical mesenchymal hamartoma. Spindle cells that comprised a predominant cellular constituent of the lesion were studied immunohistochemically and ultrastructurally. These cells were immunoreactive for vimentin, alpha-smooth muscle actin (alpha-SMA), desmin, tenascin, and alpha B-crystallin, and displayed fibroblastic or myofibroblastic ultrastructural features. These immunohistochemical and ultrastructural findings of the spindle cells were similar to those of "activated" hepatic stellate cells (Ito cells), and they confirmed and reinforced the hypothesis proposed by von Schweinitz et al. that spindle cells forming the predominant cellular constituent of mesenchymal hamartoma are derived from hepatic stellate cells, although another possibility that the spindle cells are derived from myofibroblasts in the portal tracts cannot be ruled out.

Light and electron microscopy of eruptive collagenoma.

Connective tissue nevi may be multiple or solitary, sporadic or familial. Eruptive collagenoma is a variant of the acquired collagenomas characterized by multiple sclerotic papules with an acute onset. A 13-year-old girl reported that in the past year, small asymptomatic lesions began to appear in her skin, 30 lesions were seen in the trunk, 5 in the cervical region and 1 in the face. Light microscopy with hematoxylin and eosin staining showed sparse collagen fibers, with Weigert staining diminished elastic tissue was observed. Scanning electron microscopy of the dermis showed individualized collagen fibers forming waved compact masses and not bundles. Transmission electron microscopy also showed sparse and loose collagen fibers with different diameters in cross sections.

Congenital subcutaneous dendritic cell rich lymphoepithelial hamartoma.

We present the clinical, radiologic, histologic, immunohistochemical, and ultrastructural characteristics of a congenital pretibial subcutaneous lesion composed of a mixture of T and B cells, epithelial cells, and dendritic cells, probably representing a hamartoma. After total removal, there has been no recurrence. The prominent dendritic component of this lesion, demonstrated immunohistochemically and ultrastructurally, separates the lesion from cutaneous lymphadenoma and other adnexal tumors.

Igloo-like prepuce: a peculiar aspect of smooth-muscle hamartoma of the genitalia?

We report the case of a 16-year-old boy with 'igloo-like prepuce' and hypospadia, successfully treated by asymmetrical antero-posterior postectomy. Histopathological examination consisting of classical microscopy, immuno-histochemistry and electronmicroscopy of the surgical material provided insights into the etiopathogenesis of this rare disease.

Immunohistochemical and ultrastructural markers suggest different origins for cuboidal and polygonal cells in pulmonary sclerosing hemangioma.

We report the morphological characteristics of 30 cases of sclerosing hemangioma (SH) of the lung and explore the histological origin of the major cells in these tumors. In addition to routine light and electron microscopy, immunohistochemistry was performed by using 12 monoclonal primary and 5 polyclonal primary antibodies. These included surfactant protein B (SP-B), thyroid transcription factor-1 (TTF-1), mast cell trypsin, CD68, epithelial antigen markers (high molecular weight cytokeratin, low molecular weight cytokeratin [CK-L], epithelial membrane antigen [EMA], cancer embryonic antigen), mesothelial antigen, neuroendocrine markers (neuron-specific enolase [NSE], chromogranin A, synaptophysin, calcitonin, adrenocorticotropic hormone, human growth hormone [hHG]), vimentin, and CD34. Surface cuboidal cells have short microvilli and have lamellar bodies in their cytoplasm. They can sometimes merge into multinuclear giant cells. Immunohistochemical results showed that these cells are strongly positive for SP-B, TTF-1, CK-L, EMA, and cancer embryonic antigen, whereas polygonal cells, previously also described as round or pale cells, were strongly positive for vimentin and TTF-1, and positive or weakly positive for 2 to 3 kinds of neuroendocrine markers. Sparse neuroendocrine granules and abundant microfilaments were observed in their cytoplasm. Some cell clusters in the solid regions were positive for SP-B and EMA. Mast cells existed sparsely in almost every field. Both cuboidal and polygonal cells were negative to CD34 and mesothelial antigen staining. We conclude that cuboidal cells of SH originate from reactive proliferating type II pneumocytes, which can fuse into multinuclear giant cells. Polygonal cells, as true tumor cells, likely originate from multipotential primitive respiratory epithelium and possess the capability for multipotential differentiation. The antibodies of SP-B, TTF-1, vimentin, and CK-L are very helpful to diagnosis and differential diagnosis of SH.

Angioganglioglioma: a transitional form between angioglioma and gangioglioma?

The authors describe for the first time an unusual cerebral tumor with unique clinical history, composed of 3 components: pilocytic astrocytoma, vascular proliferations similar to those described as arteriovanous malformations, and a neoplastic ganglion component. These three components were intimately entangled and created the tumor mass. Thus the authors propose the term angioganglioglioma for this entity. The relation to the historically defined anglioglioma and tumors related to ganglioglioma and dysembryoplastic neuroepithelial tumor is discussed. The authors believe that this lesion, in regard to the clinical presentation (long course of the disease, clinical symptoms), is closely associated with ganglioglioma and, with other morphological features, also to angioglioma. Further, it may constitute a new distinct clinicopathological entity with neoplastic and hamartomatous features.

Ectopic hamartomatous thymoma: a case report showing CD99+ lymphocytes and a low proliferation index.

Ectopic hamartomatous thymoma is a rare benign tumor that consists of spindle, epithelial, and adipose cell elements. We present a case of this lesion arising in the supraclavicular region of a 59-year-old man, including the characteristic immunohistochemical and ultrastructural findings. DNA flow cytometry revealed diploidy with a low proliferation index (6.73%). The tumor contained CD99+ lymphocytes; CD99 (MIC2) can serve as a useful marker of immature T cells. These findings suggest that ectopic hamartomatous thymoma may develop from the third branchial pouch or thymic anlage.

Ectopic hamartomatous thymoma: a case report with immunohistochemical and ultrastructural studies.

A case of ectopic hamartomatous thymoma (EHT) arising in the supraclavicular region of a 52-year-old male is presented. The well-defined tumor measuring 1.7x1.5x0.7 cm consisted of three components: spindle cell (70%), epithelial (25%), and adipose (5%). The spindle cell component was characterized by sheet-like, haphazard and short fascicular arrangements of bland spindle cells. Neither mitotic figures nor cellular pleomorphism were found. Admixed with, and adjacent to, the spindle cell areas was an obviously epithelial component of variable appearance, ranging from glandular spaces lined by mainly cuboidal clear cells, irregularly anastomosing cords, and strands of epithelial cells to irregular solid nests of squamous epithelium with dark and clear cytoplasm. Myoepithelial cells were also observed. Immunohistochemically, the spindle cells were strongly and diffusely positive for cytokeratins and some of them were positive for BRST2, alpha-smooth muscle actin, and CD10. The tumor was negative for S-100 protein, glial fibrillary acidic protein, and CD34. Ultrastructurally, tonofilaments and desmosomes were observed in the spindle cells. The findings indicate an epithelial origin. The patient was well without recurrence or metastasis 8 months after excision. Pathologists and clinicians should be aware of the existence of ectopic hamartomatous thymoma in the supraclavicular or suprasternal region and should differentiate it from a high-grade sarcoma, such as biphasic synovial sarcoma or glandular malignant peripheral nerve sheath tumor.

Precalcaneal congenital fibrolipomatous hamartoma: a report of four cases.

Four infants had soft, skin-colored nodules in the midline plantar region of the heels since birth. The lesions were asymptomatic, bilateral, and symmetric, and measured approximately 1 cm in diameter. Their size increased in proportion to the growth of the child. In three infants the lesions persisted at 1 year of age, while in the fourth they remained at age 12 years. The nodules were not associated with any other disease or abnormality. A review of the literature revealed only one Argentinean series comprising four cases, and two communications at international pediatric congresses by French and American authors who reported five and three cases, respectively. We describe four additional cases of precalcaneal congenital fibrolipomatous hamartoma and comment on their histopathologic and ultrastructural characteristics.

A case of localized follicular hamartoma: an ultrastructural and immunohistochemical study.

We report the case of a 22-year-old woman with a nevoid plaque that we termed localized follicular hamartoma. The plaque was noticed at puberty on a unilateral site of the face and scalp. Clinically, it revealed numerous, skin-colored to light brown papules alone and in groups, occasionally bearing a single hair. Histologically, branched epithelial nests of squamoid and/or basaloid cells were revealed in connection with the interfollicular epidermis and the upper portions of hair follicles, of which the lower portions showed normal structures. Immunohistochemically, the epithelial nests showed the keratin expression consisted with that of the infundibular epithelium. S-100-positive cells were found in the epithelial nests and the stroma. Factor XIIIa-positive dendritic cells were numerous in adjacent to the epithelial nests. Ultrastructurally, immature melanocytes with a small number of premelanosomes and Merkel cells were found in the nests. Stromal dendritic cells showed the adherent features of the cytoplasmic processes to anchoring fibrils or basal lamina of the epithelial nests. From these findings, our case is a hamartoma, which seems to be an abortive growth of secondary hair germs with a limited differentiation to the upper follicular portion.

Nasal chondromesenchymal hamartoma of infancy: the first Japanese case report.

The first Japanese case of nasal chondromesenchymal hamartoma, a rare infantile nasal neoplasm, is presented. A 4-month-old Japanese boy was referred to our Centre because of intranasal mass and oculomotor disturbance. Radiological images showed the intranasal tumor extending to the paranasal sinus, orbit, and anterior frontal fossa. Subtotal resection and radiation therapy to residual tumor were performed. There has been no recurrence of the tumor for 13 years. Histologically, the lesion demonstrated admixture of various mesenchymal elements, including cellular spindle cell stroma with occasional myxoid change, nodules of mature/immature cartilaginous tissue, focal osteoclast-like giant cells, and erythrocyte-filled spaces resembling aneurysmal bone cyst. The histology was consistent with the findings presented by McDermott et al. 1986. Immunohistochemically, the spindle cells were positive for vimentin and smooth muscle actin. Chondrocytes in the mature cartilaginous tissue were positive for S-100 and vimentin; chondrocytes in the immature cartilaginous tissue were positive for S-100, vimentin, and smooth muscle actin. Ultrastructurally, the spindle cells showed features of either fibroblast or myofibroblast.

Extensively cystic renal neoplasms: cystic nephroma, cystic partially differentiated nephroblastoma, multilocular cystic renal cell carcinoma, and cystic hamartoma of renal pelvis.

Predominantly cystic renal neoplasms have been the source of diagnostic confusion and controversy. In this review, the authors analyze the clinical and pathological features of four entities that consistently exhibit a diffusely cystic growth pattern, are strikingly similar in their gross appearances, and are not separable by preoperative imaging studies. Based on the literature, this review concludes that tumors in young children that have been classified as cystic nephroma and cystic partially differentiated nephroblastoma likely represent a single entity, and all should be considered highly cystic Wilms' tumors with little or no capacity for invasion or metastasis and diagnosed as cystic partially differentiated nephroblastoma. Conversely, cystic nephroma in adults has no discernible connection with Wilms' tumor or nephrogenic rests and should be considered a benign composite neoplasm of stroma and epithelium of unknown histogenesis, which may rarely become malignant with secondary development of a sarcoma. Multilocular cystic renal cell carcinoma appears to be unrelated to cystic nephroma and if the following criteria are met, it appears to be a neoplasm with an intrinsically cystic growth pattern, and no, or at most little, malignant potential: (1) an expansile mass is surrounded by a fibrous wall, (2) the interior of the tumor entirely is composed of cysts and septa with no expansile solid nodules, and (3) the septa contain aggregates of epithelial cells with clear cytoplasm. Cystic hamartoma of the renal pelvis is a rare, complex tumor composed of stroma with a prominent smooth muscle component and a variety of epithelial elements.

Pitfalls in the diagnosis of ectopic hamartomatous thymoma.

We describe four cases of ectopic hamartomatous thymoma with unusual morphological features. In cases 1 and 2 we found a dysplastic glandular component which was often arranged in a cribriform pattern bridging several glandular spaces. In case 2 we found solid adenocarcinomatous areas with infiltrative edges. Case 3 showed widespread smooth muscle differentiation within the spindle epithelial cell component, the presence of multiple clear cell glands which contained a distinct myoepithelial layer and an overall picture which vaguely resembled a sclerosing adenosis of the breast. Case 4 contained frequent foci of multinucleated giant epithelial cells within the markedly cellular spindle cell component: it also showed multiple, hypocellular, myxoid areas containing eosinophilic cords and pearls of squamous cells, and resembled squamous cell carcinoma with a sarcomatoid spindle cell component. We could not find any evidence of a thymic origin or of thymic differentiation in our four cases or in any other reported cases of ectopic hamartomatous thymoma. We believe that ectopic hamartomatous thymomas manifest salivary gland differentiation.

NeuN: a useful neuronal marker for diagnostic histopathology.

The monoclonal antibody A60 specifically recognizes the DNA-binding, neuron-specific protein NeuN, which is present in most neuronal cell types of vertebrates. In this study we demonstrate the potential use of NeuN as a diagnostic neuronal marker using a wide range of formalin-fixed, paraffin-embedded human surgical and autopsy specimens from the central and peripheral nervous system. After microwave antigen retrieval, almost all neuronal populations revealed strong immunoreactivity for NeuN in nuclei, perikarya, and some proximal neuronal processes, whereas more distal axon cylinders and dendritic ramifications were not stained. The stain greatly enhanced the gray matter architecture. NeuN immunoreactivity was not detected in Purkinje cells, most neurons of the internal nuclear layer of the retina, and in sympathetic chain ganglia. We examined nine gangliogliomas and 14 dysembryoplastic neuroepithelial tumors, one ganglioneuroma, and one dysplastic cerebellar gangliocytoma. The neuronal component of all of these lesions showed marked immunoreactivity for NeuN. In addition, NeuN immunoreactivity was focally seen in one of seven medulloblastomas with prominent neuronal differentiation. There was no staining of non-neuronal structures. The results indicate that NeuN immunoreactivity is a sensitive and specific neuronal marker in formalin-fixed, paraffin-embedded tissues, and may be useful in diagnostic histopathology.

Ectopic cervical hamartomatous thymoma showing extensive myoid differentiation.

Ectopic 'hamartomatous' thymoma is a rare benign neoplasm. These tumours are found in the neck and are thought to be part of a spectrum of ectopic cervical thymic neoplasia. The clinical and histological features are discussed and the literature is reviewed. An attempt is made to explain in embryological terms why such lesions appear to occur more commonly on the left side.

Hamartoma lineal con hallazgos mixtos de tricoepitelioma y tricofoliculoma / Unilateral hamartoma with mixed findings of trichoepithelioma and trichofolliculomas

Las autoras presentan el caso de una paciente joven con un raro e inusual hamartoma cutáneo de distribución lineal y unilateral aparentemente congénito, localizado en miembro superior derecho. Los estudios histológicos revelaron, en dermis, estructuras basaloides con diferenciación folicular similares a tricoepiteliomas y tricofoliculomas en la misma lesión. Se revisa brevemente la clasificación de los tumores benignos de los anexos, especialmente los de estirpe pilar