bromochloroacetic-acid and Hamartoma

Mesenchymal hamartoma is an uncommon cystic mass of the liver which occurs primarily in children. There are a few reports of its occurrence in adulthood. Here, we present two cases in female patients, 54 and 51 years old. Radiological examinations in both patients showed multiple cystic lesions in the liver. Surgically, total cystectomy was performed in the first patient, while an unroofing procedure was done in the second patient (due to misdiagnosis of the lesion as a simple cyst of the liver). On microscopic examinations of the lesion in each patient, a multilocular cyst was observed, lined by flattened epithelium and surrounded by a mesenchymal component composed of mature connective tissue, arterial and venous vascular structures, peripheral nerve bundles, and ductal structures. An immunohistochemical panel consisting of desmin, smooth-muscle actin, S-100, vimentin, CD34, carcinoembryonic antigen, pancytokeratin, cytokeratin 7, cytokeratin 8, cytokeratin 17, cytokeratin 18, cytokeratin 19, and cytokeratin 20 was applied to paraffin sections. Immunoreactivity for cytokeratin 7 and cytokeratin 19 was observed in cystic epithelium and ductal structures. Focal and patchy desmin immunoreactivity was observed in connective tissue. S-100 was positive only in peripheral nerve bundles. In conclusion, mesenchymal hamartoma of the liver in adulthood is a localized tumoral abnormality that precedes birth, and which has delayed clinical presentation. These lesions seems to be related to a maturation process. During this period of maturation, immature edematous stroma rich in mucopolysaccharides may convert to mature paucicellular hyalinized connective tissue. This maturation process may be also related to loss of premalignant potential of these tumors.

Topics: Desmin; Hamartoma; Humans; Immunohistochemistry; Keratins; Liver Diseases; Liver Neoplasms; Middle Aged; S100 Proteins; Tomography, X-Ray Computed

An extremely rare hamartomatous lesion of the juxtaoral organ of Chievitz (JOOC) in a 63 year old man is reported. The tumour appeared as a large mass in the infratemporal fossa with associated mandibular bone resorption; histologically, it was well encapsulated and composed of numerous tangled masses of benign squamous epithelial nests and mature fibrofatty tissue. There were no histological features suggestive of neoplastic transformation. A literature survey confirmed that this is the first adult case of JOOC presenting clinically as an extraoral tumour.

Topics: Biomarkers; Cheek; Hamartoma; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratins; Magnetic Resonance Imaging; Male; Middle Aged; Tomography, X-Ray Computed

A 59-year-old woman presented with epigastric pain and weight loss. Ultrasound, computed tomography, and magnetic resonance imaging scans of the abdomen showed a tumor in segments 6 and 7 of the right liver lobe, measuring 8 cm in greatest diameter. The tumor was subsequently resected, and histopathology showed a poorly differentiated adenocarcinoma immunoreactive for CA 19-9 and cytokeratin 19. In the absence of any other clinically detectable primary tumor, the lesion was diagnosed as a peripheral intrahepatic cholangiocarcinoma. In addition, multiple bile duct hamartomas were found in the surrounding parenchyma. The tumor was unrelated to Caroli disease, primary sclerosing cholangitis, ulcerative colitis, or nonbiliary cirrhosis, as demonstrated by further clinical and histopathologic investigations, but probably was associated with the presence of multiple bile duct hamartomas. To our knowledge, this is the eighth reported case of a cholangiocarcinoma associated with multiple bile duct hamartomas.

Topics: Adult; Aged; Aged, 80 and over; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; CA-19-9 Antigen; Cholangiocarcinoma; Female; Hamartoma; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male; Middle Aged

Topics: Adenoma, Bile Duct; Antibodies, Monoclonal; Bile Duct Neoplasms; Hamartoma; Humans; Keratins; Liver; Terminology as Topic

Genetic methods (both statistical and laboratory based), along with close clinical scrutiny, have led to the recent discovery that abnormal keratin genes underlie several disorders of cornification (Table 3). The ability to classify diseases based on the specific underlying gene mutation has now become a reality (e.g., the ability to distinguish IBS from EHK and to correlate palmoplantar hyperkeratosis in EHK with keratin 1 mutations vs. the lack of palmoplantar hyperkeratosis with keratin 10 mutations). Understanding how specific keratin mutations cause their associated clinical phenotypes will lead to better appreciation of the function of KIFs in epidermis in normal and disease states.

Topics: Chromosomes, Human, Pair 12; Chromosomes, Human, Pair 17; Epidermolysis Bullosa Simplex; Genetic Linkage; Hamartoma; Humans; Hyperkeratosis, Epidermolytic; Ichthyosis; Keratins; Keratoderma, Palmoplantar; Mutation; Nail Diseases; Skin Diseases

The nomenclature and pathogenesis of cutaneous cysts is discussed along the lines of their pathological properties. On the basis of histological and experimental evidence it is concluded that most cysts represent benign neoplasms derived from pluripotential cells.

Topics: Adenoma, Sweat Gland; Cysts; Dermoid Cyst; Epidermal Cyst; Hamartoma; Humans; Keratins; Pilonidal Sinus; Skin Diseases; Skin Neoplasms; Sweat Gland Diseases

We report the case of a 12-year-old girl with a smooth muscle hamartoma of the right index finger. Smooth muscle hamartoma (SMH) is a congenital, relatively common disorder typically with predominance of autochthonal arrector pili muscles. An SMH can also rarely originate from smooth muscles of vessels in palmoplantar skin with the absence of pilosebaceous units. Because of overlapping histological features, the possibility of Becker's nevus being identical or associated with SMH has often been suspected by some authors.

Topics: Biopsy; Child; Diagnosis, Differential; Female; Fingers; Hamartoma; Hand Dermatoses; Humans; Keratins; Muscle, Smooth; Skin

The histogenesis of folliculosebaceous cystic hamartoma (FSCH), including the origin of the frequently associated adipocytes and other mesenchymal components, remains unclear. There are controversial problems regarding FSCH, such as the relationship between FSCH and trichofolliculoma (TF), and the exact concept of sebaceous TF. Fourteen FSCHs and 1 sebaceous TF were revaluated for the histopathology and studied for immunohistochemical profile of various cytokeratins, hair follicular stem cell markers, and others. The nestin expression was partly upregulated in the sebaceous duct structures and the proliferating spindle cells in the surrounding connective tissue in some lesions. S-100 protein staining clarified the presence of lipogenesis in these nestin-expressed lesions, and the nestin-positive spindle cells were also seen around the immature adipocytes. Some FSCHs showed the focal follicular differentiation, where no signs of catagen or telogen stage were seen. One peculiar case showed both FSCH and TF features equally. The possibility that the adipocytes and other mesenchymal components in FSCHs originated from the nestin-positive multipotent stem cells was suggested. It is not convincing that FSCH and TF represent a chronological change in the spectrum of the same condition. Each FSCH and TF is therefore considered to be a distinctive entity. They may develop under a similar pathogenesis differing from each other in the direction of fundamental differentiation. In contrast to the TF lesions, the unusual upregulation of nestin expression is occasionally seen in FSCH lesions, including their stromas, which may thus result in the production of various kinds of mesenchymal components in FSCHs.

Topics: Adipocytes; Adult; Aged; Aged, 80 and over; Female; Hair Follicle; Hamartoma; Humans; Intermediate Filament Proteins; Keratins; Male; Middle Aged; Nerve Tissue Proteins; Nestin; Retrospective Studies; S100 Proteins; Skin Diseases

Basaloid skin tumors, including basal cell carcinoma (BCC) and basaloid follicular hamartoma, are associated with aberrant Hedgehog (Hh) signaling and, in the case of BCC, an expanding set of genetic variants including keratin 5 (encoded by KRT5), an intermediate filament-forming protein. We here show that genetic ablation of keratin 17 (Krt17) protein, which is induced in basaloid skin tumors and co-polymerizes with Krt5 in vivo, delays basaloid follicular hamartoma tumor initiation and growth in mice with constitutive Hh signaling in epidermis. This delay is preceded by a reduced inflammation and a polarization of inflammatory cytokines from a Th1- and Th17-dominated profile to a Th2-dominated profile. Absence of Krt17 also attenuates hyperplasia and inflammation in models of acute dermatitis. Re-expression of Krt17 in Gli2(tg); Krt17(-/-) keratinocytes induces select Th1 chemokines that have established roles in BCC. Our findings establish an immunomodulatory role for Krt17 in Hh driven basaloid skin tumors that could impact additional tumor settings, psoriasis and wound repair.

Topics: Animals; Blotting, Western; Carcinoma, Basal Cell; Ear; Epithelial Cells; Female; Hamartoma; Hedgehog Proteins; Hyperplasia; Immunoprecipitation; Keratinocytes; Keratins; Kruppel-Like Transcription Factors; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Skin Neoplasms; Zinc Finger Protein Gli2

Topics: Aged; Diagnosis, Differential; Epidermal Cyst; Facial Neoplasms; Filaggrin Proteins; Hamartoma; Humans; Intermediate Filament Proteins; Keratins; Male; Sebaceous Glands; Skin Diseases

Topics: Adenocarcinoma; Biomarkers, Tumor; Carcinoma, Squamous Cell; Diagnosis, Differential; Hamartoma; Humans; Inflammation; Keratins; Nasal Mucosa; Nasopharyngeal Neoplasms; Papilloma, Inverted; Paranasal Sinus Neoplasms; Polyps; Teratoma

The pathogenesis of respiratory epithelial adenomatoid hamartoma (REAH) and inverted papilloma (IP) is poorly understood, especially compared with sinonasal adenocarcinoma (SNAC). One feature of malignant glandular lesions is loss of the basal/myoepithelial layer. The immunophenotype of the basal/myoepithelial layer has not been fully examined in benign glandular lesions of the sinonasal tract.. To examine benign and malignant glandular lesions in the sinonasal tract for the immunophenotype of basal/myoepithelial cells, proliferation index, and cytokeratin and intestinal differentiation profiles.. Sinonasal adenocarcinoma (intestinal-type adenocarcinoma [ITAC] and nonintestinal type adenocarcinoma [non-ITAC]), REAH, IP, and chronic sinusitis (CS) were stained for cytokeratin (CK) 7, CK20, 34betaE12, CDX-2, p63, Ki-67, smooth muscle actin (SMA), S100 protein, and calponin.. Basal/myoepithelial cells in CS and REAH were positive for p63 and 34betaE12 but negative for SMA, S100 protein, and calponin. Proliferative activity was localized to the compartment containing p63-positive cells. Inverted papilloma demonstrated broad areas staining for p63 and 34betaE12, with intermediate proliferative activity in these areas. Sinonasal adenocarcinoma had the highest Ki-67 labeling index, and p63-positive SNACs had higher proliferation indices than p63-negative SNACs. REAH, IP, CS, and most SNACs expressed CK7. Only SNAC expressed CK20. Sixty percent of morphologic ITACs expressed CDX-2.. Basal/myoepithelial cells in CS and REAH should be considered basal and not myoepithelial cells. In benign lesions, proliferative activity is limited to the compartments with p63 staining. In SNAC and IP, p63 expression correlates with proliferation index. REAH, IP, and CS share similar immunoprofiles (CK7+, CK20-, and CDX-2-), contrasting with SNAC (CK7+, CK20+/-, CDX-2-/+).

Topics: Actins; Adenocarcinoma; Biomarkers, Tumor; Calcium-Binding Proteins; Calponins; CDX2 Transcription Factor; Cell Proliferation; Chronic Disease; Diagnosis, Differential; Epithelial Cells; Female; Hamartoma; Homeodomain Proteins; Humans; Immunohistochemistry; Immunophenotyping; Keratins; Ki-67 Antigen; Male; Membrane Proteins; Microfilament Proteins; Middle Aged; Papilloma; Paranasal Sinus Neoplasms; S100 Proteins; Sinusitis; Trans-Activators

In this report, we presented 3 cases of unusual hamartomatous nodules of the liver. These nodules were located around hepatic capsule of the left hepatic lobe and characteristically protruded from the liver. Histologically, these nodular lesions consisted of ductal structures, periductal glands, and fibrous connective tissues containing blood vessels. Smooth muscle bundles focally surrounded ductal structures. Bile-like materials were observed within some ducts. Two cases were associated with xanthogranulomatous inflammation around bile-like materials, and this inflammatory process extended from ductal lumens to periductal connective tissues. In contrast, the remaining case, which was not associated with inflammation, showed a honeycomb appearance. Ductal epithelium and periductal glands resembled biliary epithelium and peribiliary glands, respectively, and they also expressed biliary-type cytokeratins such as cytokeratins 7 and 19. These nodules shared pathologic characteristics of ciliated hepatic foregut cysts, such as their location (around the falciform ligament) and periductal smooth muscle bundles, but did not fulfill the diagnostic criteria (no ciliated cells and multilocular lesions). These hamartomatous nodules of the liver did not fit into any of the described categories of hepatic nodular lesions. At present, we speculate that these lesions might be related to developmental abnormalities of the biliary tract or embryonal foregut.

Topics: Aged; Bile Duct Diseases; Bile Ducts; Biomarkers; Cysts; Female; Hamartoma; Humans; Keratin-7; Keratins; Male; Middle Aged; Treatment Outcome

Ectopic hamartomatous thymoma (EHT) is a rare benign tumor. We present a case of EHT, which was seen as subcutaneous mass on the left supraclavicular area in a 19-year-old man. The tumor consisted of spindle cells, epithelial cells, adipose cells, and a small amount of lymphocytes, as described previously. Immunohistochemically, spindle cells were positive for keratin, a-smooth muscle actin, CD34 and vimentin, but negative for desmin and S-100 protein. Lymphocytes were positive for CD45RO but negative for CD20, CD1a, and CD99. Approximately, 5% of cells were positive for MIB-1 and no cells stained for p53 and bcl-2. Recognition of EHT is important and needs to be differentiated from high-grade sarcomas such as synovial sarcoma or glandular malignant peripheral nerve sheath tumor.

Topics: 12E7 Antigen; Adult; Antigens, CD; Antigens, CD1; Antigens, CD20; Antigens, CD34; Cell Adhesion Molecules; Choristoma; Diagnosis, Differential; Hamartoma; Humans; Keratins; Leukocyte Common Antigens; Male; Nerve Sheath Neoplasms; Sarcoma, Synovial; Soft Tissue Neoplasms; Thymoma; Thymus Neoplasms; Vimentin

Topics: Desmin; Female; Hamartoma; Humans; Immunohistochemistry; Keratins; Middle Aged; Splenic Neoplasms

Paratesticular cysts with benign epithelial proliferations (BEPs) are rare. Only 10 cases were found in a series of 431 paratesticular cysts and were classified as follows: cystadenoma, 5; papilloma, 2; and hamartoma, 3. Four cystadenomas showed multiple papillae lined by CD10+ epithelial cells with hyperchromatic nuclei. The remaining lesion showed areas with a microcystic, glandular, cribriform pattern, with small, benign glands without atypia. Urothelial papilloma presented BEPs with cytokeratin (CK) 7+ and CD10+ and CK20- umbrella-like cells. The mural papilloma was lined by proliferative cylindrical cells exhibiting strong CK7 and CD10 expression. The 3 Wolffian hamartomas were characterized by strongly CD10+ epithelium surrounded by smooth muscle cells. The consistent CD10 expression in BEPs of paratesticular cysts suggests a Wolffian origin. The differential diagnosis of paratesticular cysts with BEP vs metastatic prostatic and primary borderline or malignant tumors is discussed.

Topics: Adolescent; Adult; Aged; Cystadenoma, Papillary; Cysts; Diagnosis, Differential; Epithelium; Hamartoma; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Male; Mesonephros; Middle Aged; Neprilysin; Papilloma; Testicular Diseases

Topics: Antibodies, Monoclonal; Apocrine Glands; Biomarkers, Tumor; Ear Canal; Hamartoma; Humans; Immunohistochemistry; Keratin-7; Keratins; Sweat Gland Diseases

Gain-of-function mutations in SMO have been implicated in constitutive activation of the hedgehog signaling pathway in human basal cell carcinomas (BCCs). We used a truncated keratin 5 (DeltaK5) promoter to assess the potential role of the human M2SMO mutant in BCC development in adult transgenic mice. DeltaK5-M2SMO mouse epidermis is hyperproliferative, ex presses BCC protein markers and gives rise to numerous epithelial downgrowths invading the underlying dermis. Lesions strikingly similar to human basaloid follicular hamartomas develop, but BCCs do not arise even in elderly mice. Hedgehog target gene transcripts were only modestly upregulated in mouse and human follicular hamartomas, in contrast to the high levels detected in BCCs. Cyclins D1 and D2 were selectively upregulated in mouse BCCs. Our data suggest that the levels of hedgehog pathway activation and G(1) cyclins are major determinants of tumor phenotype in skin, and strongly implicate deregulated hedgehog signaling in the genesis of human basaloid follicular hamartomas. Expression of an activated SMO mutant in keratinocytes appears to be insufficient for the development and/or maintenance of full-blown BCCs.

Topics: Alopecia; Animals; Carcinoma, Basal Cell; Cell Differentiation; Hamartoma; Hedgehog Proteins; Humans; Hyperplasia; Keratin-15; Keratin-5; Keratinocytes; Keratins; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mutation; Phenotype; Promoter Regions, Genetic; Receptors, Cell Surface; Receptors, G-Protein-Coupled; Signal Transduction; Skin Neoplasms; Smoothened Receptor; Trans-Activators

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.

Topics: 12E7 Antigen; Antigens, CD; Antigens, CD34; CD3 Complex; Cell Adhesion Molecules; Cell Division; Choristoma; Hamartoma; Humans; Immunohistochemistry; Keratins; Leukocyte Common Antigens; Lymphocytes; Male; Microscopy, Electron; Middle Aged; Mitotic Index; Mucin-1; Thymoma; Thymus Neoplasms

We sought to investigate a novel mutation in the keratin genes assumed to be responsible for a familial case of oral white sponge nevus.. The affected family consisted of a 36-year-old woman, her 17-year-old daughter, and her 14-year-old son. Keratin 4 and 13 genes extracted from venous blood lymphocytes were amplified by using the polymerase chain reaction and directly sequenced.. Sequencing analysis of the 3 patients revealed the presence of a novel heterozygous T-to-C transition mutation in exon 1 of the keratin 13 gene, with no abnormalities detected in the keratin 4 gene.. We identified a novel heterozygous missense mutation at 332T>C in the keratin 13 gene believed to be related to the development of white sponge nevus.

Topics: Adolescent; Adult; Codon; Cytosine; Exons; Female; Hamartoma; Heterozygote; Humans; Keratins; Male; Mouth Diseases; Mutation, Missense; Thymine

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.

Topics: Actins; Apolipoproteins; Apolipoproteins D; Carrier Proteins; Glycoproteins; Hamartoma; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratins; Male; Membrane Transport Proteins; Microscopy, Electron; Middle Aged; Neprilysin; Thymoma

Topics: Diagnosis, Differential; Epithelium; Hamartoma; Humans; Keratinocytes; Keratins; Mouth Diseases; Mouth Mucosa

A nodule arising within the nevus sebaceus on the vertex of the scalp of a 68-year-old woman was histopathologically and immunohistochemically investigated. We also used immunohistochemistry to investigate the cytokeratin (CK) distribution of the outer root sheaths of normal terminal hair follicles. The nodule consisted of two parts, a main exophytic part with a lobular proliferation and a small peripheral part with the features of trichoblastoma. The main exophytic lesion consisted of lobular aggregations composed of both or either basaloid cells and clear cells with the silhouette and cytology of malignancy. The columnar clear cells were aligned in a palisade at the periphery of the aggregations of clear cells, and the aggregations located in the superficial dermis were connected to the follicular infundibular structures. Almost all of the neoplastic aggregations were diffusely positive for CK7 (OV/TLR/30), and the innermost or inner cells of the neoplastic aggregations were positive for CK17; a similar staining pattern to that in the lower portion of the outer root sheath between the A and B fringes in normal terminal hair follicles. The exophytic part of the lesion was a malignant neoplasm with differentiation mainly toward the lower segment of the outer sheath between the A and B fringes of the terminal hair follicle, namely tricholemmal carcinoma. Our case may represent a collision of two distinctive neoplasms (tricholemmal carcinoma and trichoblastoma), however, an intimate relationship between these two neoplasms also should be considered.

Topics: Aged; Biomarkers, Tumor; Carcinoma, Basal Cell; Female; Hair Follicle; Hamartoma; Humans; Immunohistochemistry; Keratin-7; Keratins; Neoplasms, Second Primary; Nevus; Scalp; Sebaceous Gland Neoplasms; Skin Diseases; Skin Neoplasms

White sponge nevus (WSN) is an autosomal-dominantly inherited form of mucosal leukokeratosis. Defects in keratins, proteins that form the stress-bearing cytoskeleton in epithelia, have been shown to cause several epithelial fragility disorders. Recently, mutations in the genes encoding mucosal-specific keratins K4 and K13 were shown to be the underlying cause of WSN. We have studied a large Scottish family with 19 persons affected by WSN in four generations. The K4 locus was excluded by genetic linkage analysis; however, genetic linkage consistent with a K13 defect was obtained. Subsequently, a heterozygous missense mutation 335A>G was detected in exon 1 of the KRT13 gene, predicting the amino acid change N112S in the 1A domain of the K13 polypeptide. The mutation was confirmed in affected family members and was excluded from 50 unaffected people by restriction enzyme analysis. These results confirm that mucosal keratin defects are the cause of WSN.

Topics: Adenine; Adolescent; Asparagine; Chromosome Mapping; Chromosomes, Human, Pair 12; Chromosomes, Human, Pair 17; Codon; Epithelium; Exons; Genetic Linkage; Guanine; Hamartoma; Humans; Keratins; Leukoplakia, Oral; Male; Mouth Diseases; Mutation, Missense; Protein Structure, Tertiary; Scotland; Serine

Eccrine angiomatous hamartoma (EAH) is an exceedingly rare benign tumor-like lesion prevalent in childhood which may produce pain and marked sweating. Although an aggressive treatment is not generally indicated, surgery may be considered in severe cases. In this report we present novel morphological findings by immunophenotyping, document the first MRI findings in EAH and emphasize the importance of preoperative imaging of such lesions.

Topics: Aged; Eccrine Glands; Hamartoma; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Leg; Male; Mucin-1; S100 Proteins; Sweat Gland Diseases

A 73-year-old woman had a linear yellowish plaque on the upper part of her right ear since birth. She presented because of the sudden growth of a nodule within the plaque. The plaque was waxy and yellowish, arching around the upper part of the ear. A reddish to yellowish large nodule was seen within the central part of the arc-shaped plaque; in addition, a small pigmented nodule, a small skin-colored nodule, and a few pigmented papules were observed in the anterior half of the arched plaque. Histopathologic examination revealed the large nodule to be sebaceous carcinoma, the small pigmented nodule to be trichoblastoma, the small skin-colored nodule to be sebaceoma with the features of trichoblastoma, a few pigmented papules to be superficial trichoblastomas due to primitive follicular induction, and the linear yellowish plaque to be nevus sebaceus. Although our literature search revealed scanty reports of definite cases of sebaceous carcinoma in nevus sebaceus, the presented case demonstrated the occurrence of sebaceous carcinoma in nevus sebaceus. Malignant neoplasms occurring in nevus sebaceous seem to be extremely rare, but care should be taken when a large nodule suddenly grows in a lesion of nevus sebaceus, especially in older adults. The presented case also suggested a close relation between trichoblastoma and sebaceoma. The cytokeratin staining pattern could not distinguish between sebaceous and follicular neoplasms in our case.

Topics: Aged; Carcinoma; Carcinoma, Skin Appendage; Ear Neoplasms; Ear, External; Female; Hamartoma; Humans; Immunohistochemistry; Keratins; Sebaceous Gland Neoplasms; Skin Diseases; Skin Neoplasms

White Sponge Nevus (WSN) is a rare, autosomal dominant disorder that predominantly affects noncornified stratified squamous epithelia. Clinically, it is characterized by the presence of soft, white, and "spongy" plaques in the oral mucosa. The characteristic histopathologic features are epithelial thickening, parakeratosis, and vacuolization of the suprabasal layer of oral epithelial keratinocytes. Mutations in keratin 4 (K4) and keratin 13 (K13) genes have already been demonstrated to be responsible for WSN; the identification of new keratin mutations in a stratified squamous epithelia closely related to epidermis is of relevance for the understanding of the biochemistry of intermediate filaments, and for genotype phenotype correlations. In this study we investigated a 27-y-old, female Italian patient, affected by white asymptomatic oral plaques. Sequence analysis revealed a 3 bp (ACA) heterozygous insertion localized in the helix initiation motif of the 1A alpha helical domain of K4. We report this new K4 gene mutation and describe an amino acid insertion, in the 1A domain, responsible for a keratin disease.

Topics: Adult; DNA Mutational Analysis; DNA Transposable Elements; Family Health; Female; Glutamine; Hamartoma; Humans; Keratins; Mouth Diseases; Mouth Mucosa; Pedigree; Protein Structure, Tertiary

Palmoplantar keratodermas are a group of heterogeneous diseases characterized by thickening, and marked hyperkeratosis, of the epidermis of the palms and soles. Palmoplantar keratodermas can be divided into four major classes: diffuse, focal, punctate, and palmoplantar ectodermal dysplasias. All forms are genetic diseases inherited as autosomal dominant disorders. We studied a patient exhibiting a localized thickening of the skin in parts of the right palm and the right sole, following Blaschko's lines, that does not fit into any classes already described. We sequenced the keratin 16 cDNA derived from skin biopsy material from affected and non affected palms. The keratin 16 cDNA sequence from lesional epidermis showed a 12 base pair deletion (309-320del), which deletes codons 104-107. The mutation is predicted to delete four amino acids, GGFA, from the V1 domain of the keratin 16 polypeptide, close to the 1A domain. Full-length keratin 16 cDNA sequence derived from the unaffected palm was completely normal, consistent with a postzygotic mutation as is suggested by the mosaicism observed. We defined this new clinical entity, "unilateral palmoplantar verrucous nevus", rather than localized or focal epidermolytic palmoplantar keratodermas, as the lesions are present only on one side of the body and follow Blaschko's lines. This study is a report of a mosaic mutation in keratin 16 and also the association of a mutation in the V1 domain of a type I keratin associated with a human disease.

Topics: Adolescent; DNA Mutational Analysis; Female; Gene Expression; Hamartoma; Humans; Keratins; Keratoderma, Palmoplantar; Mutation; Protein Structure, Tertiary; Skin Diseases

We report a case of a rare cystic renal tumor previously termed cystic hamartoma of the renal pelvis. A 53-year-old woman presented to her gynecologist with menometorrhagia. She subsequently had a computed tomographic scan that demonstrated an incidental cystic mass in the lower pole of the left kidney. Histologically, the tumor was composed of a mixture of benign mesenchymal and epithelial components. The stroma consisted of spindle cells with monomorphic nuclei and abundant eosinophilic cytoplasm that resembled smooth muscle and that reacted positively with antibodies to alpha-smooth muscle actin, desmin, and vimentin. The epithelial component was composed mostly of cysts lined by cuboidal-to-columnar epithelium. Focal dilated cysts were lined by epithelium with oncocytic features. We think that this entity is distinct from other renal tumors, including mesoblastic nephroma, cystic nephroma, or a cystic, partially differentiated nephroblastoma, and that it is best classified as a cystic hamartoma of the renal pelvis.

Topics: Female; Hamartoma; Humans; Immunohistochemistry; Keratins; Kidney Diseases; Kidney Pelvis; Middle Aged; Mucin-1; Vimentin

White sponge naevus (WSN) is a rare autosomal dominant condition which is characterised by benign, white spongy plaques (oral leukokeratoses) affecting non-cornifying, wet mucosa. WSN shares several ultrastructural characteristics (eg, epithelial thickening, acanthosis, keratin filament aggregation) with a number of epithelial disorders caused by mutations in keratin genes and to-date two mutations, one in each of the mucosal specific keratins, K4 and K13, have been identified as the molecular basis of the disorder.. To identify the molecular basis of WSN in two families with a history of the disease.. Two novel mutations were identified in helix initiation motif of K13. A T-to-C transition was found in the affected members of one family which is predicted to change leucine115 to proline. In the second family, a similar T-to-C transition was found in codon 108 which is predicted to change methionine to threonine in the protein sequence. These changes were not found in 50 unrelated, unaffected individuals.. The mutations in the helix initiation motif of K13 are the cause of WSN in these families. These cases confirm mutations in the mucosal specific keratins as a significant cause of the disorder.

Topics: Adolescent; Amino Acid Motifs; Amino Acid Substitution; Child; Female; Hamartoma; Humans; Keratins; Leucine; Male; Methionine; Mouth Mucosa; Mucous Membrane; Pedigree; Point Mutation; Proline; Threonine; Vagina

Mesenchymal hamartoma is a rare liver lesion. This lesion was found in a 7-month-old girl with high serum alphafaetoprotein serum levels and was composed of loose connective tissue containing a certain number of epithelial cells of biliary or hepatic origin. Immunohistochemical studies showed that cytokeratins 7 and 19 were localized in bile duct epithelium. The ultrastructural study showed that the hamartoma was composed of well differentiated ductal structures surrounded by a myxoid mesenchyma with cysts formed either from degenerative mesenchymal areas or from dilated ducts. Flow cytometric analysis of nuclei from frozen tissue revealed that the lesion was DNA aneuploid, with a DNA index of 1.28.

Topics: alpha-Fetoproteins; Aneuploidy; DNA; Female; Flow Cytometry; Hamartoma; Humans; Immunohistochemistry; Infant; Keratin-7; Keratins; Liver Diseases; Mitotic Index

Cytokeratin (CK) patterns and albumin messenger RNA (mRNA) are investigated in 24 patients with benign hepatic lesions (7 patients with focal nodular hyperplasia [FNH], 10 with hepatocellular adenomas [HA], 1 with biliary hamartoma, 4 with biliary cysts, 2 with cystadenomas) and in 8 patients with cystadenocarcinoma, a rare liver malignancy. The lesions and surrounding tissue of the hepatocytic components expressed CK 8 and 18 at immunohistochemistry, whereas the biliary elements evidenced CK 8 and 18 and CK 7 and 19. The albumin mRNA, as detected by in situ hybridization (ISH), revealed different distributions in the hepatocytes of FNH and HA. In the benign biliary lesions, the normal hepatocytes surrounding the tumors expressed albumin mRNA, whereas the biliary structures did not. Interestingly, in the cystadenocarcinomas, albumin mRNA was observed not only in the hepatocytes of residual parenchyma, but also in neoplastic bile duct cells lining the carcinomatous cysts; no signal was identified in the nonneoplastic biliary elements. This indicates that cystadenocarcinomas have a mixed biological phenotype and suggests they could arise either from pluripotent cells or from neoplastic cells that reacquire epigenetic features. Our results suggest two possible diagnostic applications for albumin ISH: on routine sections, it could represent an important tool for distinguishing between cystadenoma and cystadenocarcinoma; and on fine needle biopsy specimens, it could reduce uncertainty between FNH and HA.

Topics: Adenoma; Adolescent; Adult; Aged; Albumins; Biliary Tract Neoplasms; Biomarkers, Tumor; Cell Differentiation; Cystadenocarcinoma; Cystadenoma; Cysts; Diagnosis, Differential; Female; Gene Expression; Hamartoma; Humans; Hyperplasia; Immunoenzyme Techniques; In Situ Hybridization; Keratins; Liver; Liver Diseases; Liver Neoplasms; Male; Middle Aged; Neoplasm Proteins; Phenotype; Protein Isoforms; RNA Probes; RNA, Complementary; RNA, Messenger; RNA, Neoplasm; Stem Cells

Congenital epithelial tumours of the salivary glands are very rare. The Salivary Gland Registry maintained in the Department of Pathology. University of Hamburg, contains only three cases among a total of 6,646 salivary gland tumours from the years 1965-1994. The three cases were classified as congenital basal cell adenoma, two of the parotid gland and one of the submandibular gland. Histologically, the three adenomas were similar in structure to the adult counterpart of basal cell adenoma with solid, trabecular or tubular (duct-like) patterns. In some cystic spaces of the duct-like structures PAS- and Astra blue-positive substances were secreted. On immunocytochemistry, the luminal duct-like cells showed membranous expression of cytokeratins 3, 5, 6, 7, 13 and 19. In the isomorphic basaloid cells of the solid and trabecular cell nests few cells expressed cytokeratin. On the outside of the solid cell nests there were smaller elongated myoepithelial-like cells, which expressed cytokeratin 14 and vimentin. Cytokeratins 1, 2, 4 and 18 were not expressed. The pattern of expression reflects the different stages of maturity of the tumour cells and is related to the development of the salivary glands until the end of the 3rd embryonal month with an arrest of further cell differentiation. No acinic cells, invasive growth, recurrence or metastases were observed. The differential diagnosis includes other congenital salivary gland tumours, such as hybrid basal cell adenoma-adenoid cystic carcinoma, sialoblastoma or embryoma, carcinoma, hamartoma and teratoma.

Topics: Adenoma; Carcinoma; Diagnosis, Differential; Female; Hamartoma; Humans; Immunohistochemistry; Infant, Newborn; Keratins; Male; Microscopy, Electron; Parotid Neoplasms; Periodic Acid-Schiff Reaction; Submandibular Gland Neoplasms; Teratoma; Vimentin

We report two cases of a previously unrecognized neoplasm, each characterized by prominent lobular configuration in the subcutaneous tissue. Within the neoplasms were distinctive garland-shaped structures composed of glial fibrillary acidic protein (GFAP) positive cells with indistinct borders, encased in concentric loops of fine collage fibers. In some areas, the neoplastic cells were distributed in small lacunae. The extracellular space between the collagenous tissue and the cells was filled with copious myxoid matrix. One of the neoplasms also demonstrated areas with spindle cells which resembled leiomyoma. Immunohistochemistry was negative for smooth muscle actin (1A4), muscle actin (HHF35), S-100 protein, desmin, cytokeratin, KP1, and epithelial membrane antigen (EMA.) Currently, both patients are free of recurrence or metastasis 2 and 4 years after primary surgical excision. The neoplasms, which we term benign polymorphous mesenchymal tumor of soft parts (BPMT), should be distinguished from ossifying fibromyxoid tumor of soft parts, extraskeletal mesenchymal chondrosarcoma, neoplasms arising in ectopic breast tissue and mixed tumor of the skin.

Topics: Actins; Adult; Desmin; Female; Glial Fibrillary Acidic Protein; Hamartoma; Humans; Immunohistochemistry; Keratins; Middle Aged; Mucin-1; S100 Proteins

Tumor of the follicular infundibulum is a rare proliferation of cells and its histogenesis or differentiation at the morphological level has been the subject of some controversy. In recent years cytokeratins have been recognized as important markers of epithelial differentiation, and of late new retrieval methods have meant it is possible to detect them in formalin-fixed and paraffin-embedded tissue. Four patients were studied, the ages ranging between the 2nd and 7th decade. The tumors were all located in the head and neck and in one case the lesion developed in a pre-existing sebaceous nevus. The morphological investigation revealed a flat, proliferation of polygonal, pale eosinophilic cells connected to epidermis or follicular infundibulum and with a centrally located nucleus. In addition, a few ductal structures resembling sebaceous ducts were seen and in one case a hair germ papilla and a follicular papilla was noted. Immunohistochemical investigations with antibodies against cytokeratins revealed differentiation comparable to that in the fetal follicular isthmus and, in one case, also differentiation in keeping with the fetal follicular infundibulum.

Topics: Adult; Aged; Biomarkers, Tumor; Carcinoma, Basal Cell; Cell Transformation, Neoplastic; Cytoplasm; Female; Hair Follicle; Hamartoma; Head and Neck Neoplasms; Humans; Keratinocytes; Keratins; Male; Middle Aged; Precancerous Conditions; Sebaceous Glands; Skin Neoplasms

White sponge nevus (WSN) is a benign autosomal dominant disorder which affects non-cornifying stratified squamous epithelia (MIM 193900) (ref. 1). Phenotypically it presents as white 'spongy' plaques (oral leukokeratoses), most commonly in the mouth but also reported in the esophagus and anogenital mucosa. Histologically, the plaques show evidence of hyperproliferation, acanthosis and tonofilament aggregation. These types of pathogenic changes are characteristic of many of the epidermal keratin disorders. Keratins are expressed in pairs by epithelial cells in a tissue and cell specific manner. The major differentiation specific keratins of the buccal mucosa, nasal, esophageal and anogenital epithelia are K4 and K13 (ref. 7). The tissue distribution and nature of the lesions in patients affected by WSN suggested that mutations in K4 and/or K13 might be responsible for this disorder. We have now confirmed this hypothesis and report here a three base-pair (bp) deletion in the helix initiation peptide of K4 in affected members from two families with this condition.

Topics: Amino Acid Sequence; Base Sequence; Cloning, Molecular; DNA Mutational Analysis; DNA, Complementary; Epithelium; Female; Genes, Dominant; Hamartoma; Humans; Keratins; Leukoplakia, Oral; Male; Molecular Sequence Data; Mouth Mucosa; Pedigree; Sequence Deletion; Tongue

Although pathogenic keratin mutations have been well characterized in inherited epidermal disorders, analogous defects in keratins expressed in non-epidermal epithelia have yet to be described. White sponge nevus (WSN) is a rare autosomal dominant disorder of non-cornifying squamous epithelial differentiation that presents clinically as bilateral white, soft, thick plaques of the oral mucosa. Less frequently the mucous membranes of the nose, esophagus, genitalia and rectum are involved. Histopathological features, including epithelial thickening, parakeratosis, extensive vacuolization of the suprabasal keratinocytes and compact aggregates of keratin intermediate filaments (KIF) in the upper spinous layers, resemble those found in epidermal disorders due to keratin defects. We analysed a multigenerational family with WSN and found cosegregation of the disease with the keratin gene cluster on chromosome 17. We identified a missense mutation in one allele of keratin 13 that leads to proline substitution for a conserved leucine. The mutation occurred within the conserved 1A region of the helical rod domain, which is critical for KIF stability and is the site of most pathogenic keratin mutations. This mutation enlarges the spectrum of keratins with disease-causing defects to include mucosally expressed keratin 13, and extends the known keratin diseases to disorders of non-cornifying stratified squamous epithelia.

Topics: Amino Acid Sequence; Base Sequence; Chromosomes, Human, Pair 17; DNA Mutational Analysis; Epithelium; Female; Genetic Linkage; Hamartoma; Humans; Keratins; Leukoplakia, Oral; Male; Molecular Sequence Data; Mouth Mucosa; Multigene Family; Pedigree; Point Mutation

A 62-year-old man presented with a nodule 2 cm in diameter on his left cheek, which he had had since childhood. Histological examination showed a circumscribed dermal nodule composed of sebaceous lobules attached to sebaceous ducts and to an infundibular cyst-like structure connected to the epidermis. The wall was lined with squamous epithelium with a stratum granulosum. This structure was reminiscent of a sebaceous follicle. In addition, a melanocytic naevus of the compound type was found. Immunohistological investigations of the tumour with various cytokeratins revealed a pattern of expression characteristic for the mature sebaceous follicle.

Topics: Biomarkers, Tumor; Cheek; Diagnosis, Differential; Epidermal Cyst; Facial Dermatoses; Hamartoma; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Sebaceous Glands; Skin

Nevus sebaceus, considered to be a hamartoma, is known to develop several secondary hyperplastic and neoplastic proliferations. By the use of immunohistochemical studies, we were able to describe a sometimes very striking increase of Merkel cells in nine of 19 nevi sebacei. Only nevi sebacei that formed follicular germ structures and trichoblastomas showed a Merkel cell hyperplasia. In the hyperplastic epidermis of some cases a slight hyperplasia of singular Merkel cells was observed. In foci with follicular germs and trichoblastomas, however, the Merkel cells were much more abundant and sometimes arranged in clusters. Merkel cell hyperplasia is likely to represent another facet of hamartomatous hyperplasia in nevi sebacei. Our observation that trichoblastomas in nevus sebaceus possess, as a rule, hyperplasia of Merkel cells, might be an additional aid to distinguish these tumors from basal cell carcinomas, which are usually devoid of Merkel cells. Furthermore, our findings are a hint that development of follicular germs and trichoblastomas in nevi sebacei may be promoted by Merkel cells.

Topics: Adolescent; Carcinoma, Basal Cell; Cell Count; Child; Chromogranin A; Chromogranins; Coloring Agents; Diagnosis, Differential; Epidermis; Hair Follicle; Hamartoma; Humans; Hyperplasia; Immunohistochemistry; Keratins; Merkel Cells; Neoplasms, Basal Cell; Skin; Skin Abnormalities; Skin Neoplasms

An unusual and, apparently, hitherto undescribed congenital lesion of the scalp which proved to be heterotopic meningothelial tissue is reported, and its clinical, morphological, and theoretical implications are reviewed. A 14-month-old male infant exhibited a soft tissue lesion on the midline of the parietal scalp since birth. The lesion had grown in size since birth. Histological examination showed an admixture of mature adipose tissue, bands consisting of bundles and small nodules of dense collagen, both enclosed and bordered by rests and strands of meningothelial cells. A network of vessel-like channels lined by plump hyperchromatic cells with spindle-shaped nuclei and occasionally multinucleated giant cells was one of the prominent features. Immunohistochemically, these cells were positive for vimentin, but staining was negative for EMA and all other antibodies tested. A fibrocollagenous stalk via bony defect showed no arachnoid cell rests. The authors believe that the herein described lesion and the hamartoma of the scalp described by Suster and Rosai (1990) may represent varying morphological expressions of a pathogenetically related process. Precautions appropriate to the possibility of intracranial extension must be taken at the time of surgery.

Topics: Antigens, Neoplasm; Collagen; Hamartoma; Humans; Immunohistochemistry; Infant; Keratins; Male; Meninges; Scalp; Skin Neoplasms; Soft Tissue Neoplasms

Cytogenetic analysis of two pulmonary chondroid hamartomas and nine breast adenofibromas revealed clonal chromosome aberrations in both hamartomas and in four breast tumors. To determine lineage of the cells with chromosome aberrations, a combined immunohistochemical/cytogenetic approach was developed that enabled simultaneous ascertainment of cytogenetic aberrations and immunohistochemical features in individual cells. Immunohistochemical/cytogenetic evaluation of one hamartoma and two adenofibromas demonstrated that neoplastic proliferation, in each case, was confined to the mesenchymal (stromal) component, whereas epithelial cells appeared to be reactive. Cytogenetically abnormal short-term cultures of the remaining hamartoma and another of the breast adenofibromas were composed entirely of mesenchymal elements, indicating mesenchymal clonality in those tumors as well. Our findings support redesignation of pulmonary chondroid hamartomas as 'pulmonary chondromas' and suggest that carcinomas developing within fibroadenomas arise from reactive epithelial proliferation. Combined immunohistochemical/cytogenetic analysis might be useful in the development of novel therapeutic approaches that selectively target neoplastic populations within solid tumors.

Topics: Adenocarcinoma; Breast Neoplasms; Cell Transformation, Neoplastic; Chromosome Aberrations; Hamartoma; Humans; Immunohistochemistry; Karyotyping; Keratins; Lung Neoplasms; Mesoderm; Trisomy; Tumor Cells, Cultured; Vimentin

We report a rare case with a pedunculated nodule on the nasal septum, which seems a kind of follicular hamartoma with a pedunculated appearance. Our case was a 77-year-old Japanese male with an 11 x 11 x 10 mm sized, skin-to-pink colored, pedunculated nodule on the center of his nasal septum. Histopathological study revealed the nodule to be a well-formed dilated hair follicle at the central pore of the tumor, where keratin debris and vellus hairs were present. In addition, epithelial cells forming long thin strands or immature follicle-like structures had proliferated multifocally from the epidermis of the wall of the central follicle to the peripheral epidermis. One distinctive feature was the formation of a primary germinal bud with thick concentric collagen fibers and sparse elastic fibers. Although a combined tumor of trichofolliculoma with highly-graded desmoplasia, multiple trichogenic trichoblastomas, and perifollicular fibromas was suggested, calling it a pedunculated follicular hamartoma seemed more useful because the pathological features were basically similar to reported follicular hamartomas and the clinical feature was so distinctive.

Topics: Aged; Cell Division; Collagen; Hair; Hamartoma; Humans; Immunoenzyme Techniques; Keratins; Male; Nasal Septum; Nose Neoplasms; Skin Neoplasms

Four new cases of ectopic hamartomatous thymoma are presented. The tumor occurred either superficially or deep in the area of the sternoclavicular joint and consisted of solid islands of squamous epithelium which blended with spindled cells. Cysts lined by squamous epithelium, small glands, and fat also occurred in variable amounts. Both the spindled and epithelial regions of the tumor expressed keratin and muscle actin, but neither desmin nor S100 protein. The tumor probably originates from thymic anlage associated with the third pharyngeal pouch (thymus III), although origin from other structures such as thymus IV and the cervical sinus of His are discussed. Our experience indicates that the large size and extreme cellularity of the spindled portion of some tumors may result in the mistaken diagnosis of sarcoma.

Topics: Actins; Adult; Aged; Carcinoma; Desmin; Diagnosis, Differential; Hamartoma; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; S100 Proteins; Sarcoma, Synovial; Thymoma; Thymus Neoplasms

The case of a 61-year-old woman with a surgically resected solitary cholangiocarcinoma of the liver is reported, where many discrete multiple bile duct hamartoma (MBDH) were also seen. The latter is a congenital lesion of the liver that potentially may be confused with widespread metastatic disease. The relationship between cholangiocarcinoma and MBDH was studied histologically by the use of an immunoperoxidase technique for cytokeratin. MBDH was strongly positive for cytokeratin, while the neoplasm showed this to a lesser extent, but a clear continuity between the MBDH epithelial cells and those of the neoplasm was demonstrated by the use of this technic. The potential use for the various cytokeratins in the differentiation of primary from secondary liver tumors, is discussed. This differentiation is a significant problem to the pathologist. Although cholangiocarcinoma may, on occasion, be associated with various congenital lesions of the bile ducts, the association with MBDH is extremely rare, this being only the third reported case.

Topics: Adenoma, Bile Duct; Bile Duct Neoplasms; Bile Ducts; Bile Ducts, Intrahepatic; Carcinoembryonic Antigen; Female; Hamartoma; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Membrane Glycoproteins; Middle Aged; Mucin-1; Neoplasms, Multiple Primary

The histological and ultrastructural features of a sclerosing epithelial hamartoma are described. By electron microscopy, epithelial cords formed by basal-like cells and epithelial cysts with a pattern of keratinization similar to that of normal epidermis or of follicular infundibula were seen. By conventional light microscopy, continuities were found between the epithelial cords and the overlying epidermis. The stroma was found to be fibrous and contained some fibroblasts or possibly myofibroblasts with bundles of microfilaments. The data are interpreted with respect to the origin of the neoplasm, its line of differentiation, and its sclerosing behavior.

Topics: Actin Cytoskeleton; Adult; Biopsy; Cheek; Facial Neoplasms; Female; Fibroblasts; Hamartoma; Humans; Keratins; Sclerosis; Skin; Skin Neoplasms

Histological, histochemical and immunohistochemical findings were studied in 40 cutaneous biopsies from 7 patients with Cowden's disease. Most facial biopsies showed a spectrum of trichilemmomas and related follicular malformations, including cylindrical trichilemmomas, lobulate trichilemmomas (14 lesions), and a keratinizing type sharing features with inverted follicular keratosis. One facial growth showed trichilemmomal changes without apparent follicular origin. Studies for common papilloma virus structural antigens were negative, apart from a typical common wart in one patient. Immunohistochemical studies in 6 facial trichilemmomas and acral keratoses, using a panel of anti-keratin antibodies, disclosed only abnormal differentiation with lack of large keratins in the lobulate trichilemmomas. Nine biopsies revealed a distinctive type of fibroma characterized by an organized pattern of interwoven fascicles of collagen bundles with a laminated or tortuous appearance, embedded in abundant mucin. A number of fibromas showed striking hyalinization; these may represent a second microscopic hallmark of Cowden's disease in addition to facial trichilemmomas.

Topics: Antigens, Viral; Biopsy; Facial Neoplasms; Fibroma; Hamartoma; Humans; Keratins; Skin; Skin Neoplasms; Staining and Labeling; Syndrome

Topics: Adult; Biopsy; Diagnosis, Differential; Female; Fibroma; Follow-Up Studies; Hair; Hamartoma; Humans; Keratins; Male; Melanins; Middle Aged; Mucins; Neurofibroma; Sensory Receptor Cells; Skin; Skin Neoplasms