Benign Follicular Neoplasms Research Articles

Distinguishing Trichoepitheliomas from Basal-Cell Carcinomas

Trichoepitheliomas, benign follicular neoplasms, are often difficult to distinguish, both clinically and histologically, from basal-cell carcinomas.

Bcl-2 expression reliably distinguishes trichoepitheliomas from basal cell carcinomas.

Trichoepitheliomas (TE) are benign follicular neoplasms which are frequently confused with basal cell carcinomas (BCC). It is important to distinguish these entities precisely, as the treatments and prognoses are different. To this end, we stained a series of formalin-fixed, paraffin-embedded specimens of unequivocal TE and BCC with antibodies directed against bcl-2, an oncogene associated with programmed cell death, and known to be overexpressed in some malignant tumours. The TE showed staining of tumour cells limited to the outermost layer of the proliferation. The BCC tumour cells demonstrated diffuse staining throughout the tumour nodules. This difference in staining pattern was then applied to more equivocal cases, and seemed clearly to separate the entities. The observed findings may prove to be of diagnostic help in distinguishing borderline cases, and also offer some possible explanations for the biological differences between these neoplasms.

Proton magnetic resonance and human thyroid neoplasia. II: Potential avoidance of surgery for benign follicular neoplasms.

Thyroid cancer is rare, but many thyroidectomies continue to be performed simply to exclude a diagnosis of malignancy. The purpose of this study was to determine the potential financial savings associated with the use of proton magnetic resonance analysis of follicular neoplasms. Proton magnetic resonance spectroscopy was performed on tissue obtained at the time of surgery from 98 consecutive solitary or dominant thyroid nodules. Fine-needle biopsies were also performed on operative specimens, and the tissues assessed by proton magnetic resonance; these spectra were then compared with those obtained from tissue specimens. An estimate of potential savings was obtained by comparing the magnetic resonance data with the indications for surgery and pathology on all patients having thyroidectomy over a 10-year period. Proton magnetic resonance spectroscopy was able to distinguish between normal thyroid tissue and invasive thyroid cancer with 100% specificity. Benign follicular adenomas fall into two groups: 44% having a spectral pattern comparable with normal thyroid, and the remaining 56% demonstrating an altered spectral pattern more comparable to the malignant magnetic resonance profile. Proton magnetic resonance spectroscopy on fine-needle biopsy specimens produced spectra similar to those from tissues from the same patient. From a fine-needle biopsy specimen, proton magnetic resonance spectroscopy can identify a group of benign follicular adenomas with spectral profiles akin to those of normal thyroid cells, thus avoiding the need for unnecessary surgical excision. The potential savings in one surgical unit alone were over $1 million in 10 years.

Proton magnetic resonance and human thyroid neoplasia I: Discrimination between benign and malignant neoplasms

purpose: Thyroid nodules are very common, yet the vast majority are biologically benign. The extreme difficulty facing the clinician selecting potentially malignant thyroid nodules for surgery was the subject of a recent editorial by Ernest L. Mazzaferri in the American Journal of Medicine (93: 359–362, 1992). Here we evaluate the potential of proton magnetic resonance spectroscopy ( 1H MRS) to provide a solution to this problem. patients: Thyroid tissue from fifty-three patients undergoing partial or total thyroidectomy for solitary thyroid nodules were assessed by 1H MRS. results: When compared with the histologic diagnosis, 1H MRS distinguished normal thyroid tissue (n = 8) from invasive papillary (n = 9), anaplastic (n = 1), and medullary (n = 1) carcinomas with P values of < 0.0001, based on altered cellular chemistry. The same magnetic resonance (MR) criteria categorized pathologically proven follicular carcinoma (n = 8) (established as such by the presence of capsular or vascular invasion at the periphery of the tumor, or by the presence of metastases in the patient) with the other thyroid cancers ( P < 0.0001). All other “benign” follicular neoplasms (n = 34), including five atypical follicular adenomas, were assessed by the same 1H MRS criteria and found to fit into one of the two above categories, viz. analogous to benign or malignant thyroid tissue. conclusions: Proton MRS has the potential to separate out a group of truly benign follicular neoplasms from follicular tumors (both follicular adenomas and follicular carcinomas) that have an atypical follicular pattern on cytologic examination. This is the first report of an objective diagnostic procedure that has the potential to obviate surgical excision in a significant number of patients with benign follicular adenomas, independent of exhaustive histopathologic assessment.

The thyrotropin receptor (TSH-R) is not an oncogene for thyroid tumors: structural studies of the TSH-R and the alpha-subunit of Gs in human thyroid neoplasms.

The development and progression of thyroid tumors are associated with phenotype-specific mutations of genes involved in growth control. Thyroid cell growth is controlled in part by the interaction of TSH with its receptor, with subsequent activation of the GTP-binding protein and its effector, adenylyl cyclase. The resulting increase in intracellular cAMP stimulates growth in thyrocytes. The TSH receptor (TSH-R) is a seven-transmembrane domain receptor. Intracellular domains of the TSH-R important for signal transduction and which may serve as targets for mutational activation have been defined. In addition, mutations at specific loci of the alpha-subunit of G-protein in human thyroid tumors have been described. We examined 92 benign and malignant neoplastic thyroid tissues for possible mutations of the intracytoplasmic domains of the TSH-R known to be involved in signal transduction and for mutations within the hot spots of Gs alpha. Screening was carried out by single strand conformation polymorphism (TSH-R) or denaturing gradient gel electrophoresis (Gs alpha) of polymerase chain reaction-amplified tumor DNA. No mutations were observed in the cytoplasmic domains of the TSH-R, except for a neutral base substitution in codon 460 (GCG [Ala]-->GCA [Ala]) in 3 tumors, which was also present in constitutional DNA from the affected individuals. A heterozygous mutation of codon 201 of Gs alpha (GGT [Arg]-CAT [His]) was observed in a nodule from an adenomatous goiter. In addition, a codon 227 mutation (CAG [Glu]-CAT [His]) was identified in a follicular adenoma. We conclude that mutational activation of the intracytoplasmatic domains of the TSH-R is not a significant mechanism of thyroid tumorigenesis, whereas putative activating mutations within exons 8 and 9 of Gs alpha occur infrequently in some benign follicular tumors.

Oncogene expression in follicular neoplasms of the thyroid

Oncogene expression has been found to be a potential marker for aggressive biologic behavior in certain tumors. We studied 21 follicular adenomas and 20 follicular carcinomas by immunocytochemistry utilizing specific monoclonal antibodies against HER-2/neu and c-myc oncogenes. Survival data were obtained from our institution's tumor registry. No expression of the HER-2/neu oncogene was found in the specimens studied. Cytoplasmic staining for c-myc was observed in 3 of 21 adenomas (14%) and 9 of 20 (45%) carcinomas (p < 0.05). The incidence of local, regional, and distant metastases was not significantly different in c-myc (+) and c-myc (-) patients. The c-myc oncogene is expressed more often in malignant than in benign follicular neoplasms of the thyroid, but its expression does not appear to be a good prognostic indicator.

Basaloid follicular hamartoma: Solitary and multiple types

Multiple skin tumors often show autosomal dominant inheritance; solitary neoplasms are typically nonhereditary. The purpose of this study was to investigate a possible hereditary pattern in patients with multiple and solitary basaloid follicular hamartomas. Four new familial cases of multiple basaloid follicular hamartomas and 56 solitary nonhereditary examples were identified and their inheritance pattern recorded. Clinically, basaloid follicular hamartomas were typically 1 to 2 mm, smooth facial papules. Histologically, they were well-circumscribed lesions composed of anastomosing strands of squamoid and basaloid cells in a loose stroma. Horn cysts and pigmentation were common. No significant association with other cutaneous or internal disease was found. Basaloid follicular hamartoma, a unique benign follicular tumor, was often diagnosed previously as trichoepithelioma or basal cell carcinoma. It is another cutaneous neoplasm in which patients with multiple lesions show autosomal dominant inheritance, whereas solitary growths with identical clinical, microscopic, and biologic features are nonhereditary.

Absence of human leukocyte antigen molecules in skin tumors and some cutaneous appendages: Evidence using monoclonal antibodies

Four highly sensitive monoclonal antibodies were assessed for their use in an immunoperoxidase technic on cutaneous sections. Three, B2, C23, and 2A1, were found to discriminate basal cell carcinomas (BCCs) from benign proliferative disorders of skin, and 2A1, a monoclonal antibody against the heavy chain component of class 1 human leukocyte antigens (HLA) for the first time directly demonstrated the absence of this structure from the malignant cell membrane. However, the deeper portions of hair follicles were also found to be unlabeled, and further study of benign follicular tumors which may histologically mimic basal cell carcinomas is suggested.

Three-dimensional hair follicular differentiation of a trichilemmoma cell line in vitro.

A cell line was established in vitro from a benign hair follicular tumor of human trichilemmoma. Individual and organized cellular differentiation of this cell line was studied. When these cells were cultured for a long time (more than 3 weeks) without subculture, they started to pile up spontaneously. A part of the pile became indented and simultaneously the opposite side of the indentation budded out. The bud slowly elongated 2 to 3 mm in length in 8 to 12 weeks in culture. Light and electron microscopy revealed the internal structure of piles and elongated buds to be a three-dimensional hair follicular structure. The cells in the outermost layer were least mature. These were cuboid in shape and contained glycogen. The cells in the middle layer were more differentiated with a decreased amount of glycogen and an increased number of tonofilaments and desmosomes. The cells in the innermost layer were most differentiated. Cells were flat in shape and highly convoluted. The cell membrane was thickened as observed in cornified cells in vivo. These organized differentiations were also confirmed by histochemical and immunocytochemical studies; using a fluorescent thiol reagent, N-(7-dimethylamino-4-methylcoumarinyl)-maleimide method, free sulfhydryl groups were detected but disulfide bonds were absent in the early cell culture. Disulfide bonds increased slowly and accumulated in the innermost layer of piles. Accumulation of keratin substances, detected by indirect immunofluorescence method using anti-human keratin antibody, was also observed specifically in the piles. These results suggest that an established cell line of human trichilemmoma spontaneously produced, without stromal influence, hair follicular structures as well as individual cell differentiations in vitro as do trichilemmal (hair follicular) cells in vivo.

Trichilemmoma. Benign follicular tumor or viral wart?

Trichilemmoma is a follicular tumor because of its resemblance to follicular outer root sheath, overlapping features with other tumors in the spectrum of benign follicular neoplasms, occurrence as multiple dominantly inherited and solitary noninheritable tumors, and occasional complication of organoid nevus. The dangerous misinterpretation that trichilemmomas are viral warts, unsupported by scientific evidence, has harmed patients. All electron-microscopic, immunologic, and clinical transmission attempts to demonstrate viral etiology of trichilemmoma have failed. If trichilemmomas were simply old warts, we might expect to see them frequently in children, extrafacially, of long duration, associated with multiple authentic ("young") warts, as multiple lesions, and associated with authentic warts in patients with Cowden's syndrome (multiple trichilemmomas). Actually, trichilemmomas are rarely seen in children, extrafacially, of long duration, associated with multiple authentic warts, as multiple lesions in patients without Cowden's syndrome, and associated with authentic warts in Cowden's syndrome. Unfortunately, patients with multiple trichilemmomas, Cowden's syndrome, and associated internal disease have been passed off as "simply old viral warts." The missed opportunity to identify women with a 50% risk of breast cancer is a disservice to the patient, to say nothing about malpractice implications for the physician when generally accepted medical standards are not applied.

Pilar Sheath Acanthoma

A newly recognized, benign follicular tumor occurred in nine patients who ranged in age from 46 to 75 (median, 55) years. The neoplasms were solitary, asymptomatic, skin-colored nodules with a central pore-like opening plugged with keratin. All lesions had been present for years. Eight were on the skin of the upper lip and one was on the forehead. Histologically, a central cystic cavity showing epidermoid keratinization extended from the surface into the deep cutis. Multiple tumor lobules that were composed of hair sheath epithelium extended from the cyst wall into the surrounding corium. This neoplasm, which we have named "pilar sheath acanthoma," must be differentiated from trichofolliculoma and dilated pore.