Benign Follicular Neoplasms Research Articles

Tumor of Follicular Infundibulum: Clinical Presentations and Productive Stains

More than a half-century ago, researchers first described tumor of the follicular infundibulum (TFI), a benign follicular adnexal tumor. TFI usually is

Agminated pigmented matricoma: a case of a unique tumor with a multifocal appearance composed of neoplastic matrical cells with a significant component of melanocyte

Matricoma is benign follicular neoplasm with the same constituent cells as pilomatricoma but with a different silhouette. Matricoma consists mostly of solid aggregations of matrical cells, as opposed to pilomatricoma, which is often a cystic lesion. We herein describe a case of agminated pigmented matricoma. A 27-year-old Japanese man visited our hospital complaining of three separate, pigmented, firm and sessile nodules on the back. Histopathologic examination revealed mostly solid aggregations of matrical and supramatrical cells located mainly within the dermis and the upper part of the subcutis. Shadow cells were present mostly within the aggregations. At higher magnifications, occasional indication of inner sheath differentiation, in addition to differentiation toward hair in the form of shadow cells, could be discerned in the center of the aggregations. The matrical and supramatrical cells within the aggregations were relatively uniform in size and shape, and contained several mitotic figures. Heavily pigmented melanocytes were present within the aggregations of matrical and supramatrical cells, and heavily pigmented melanophages were found in adjacent stroma. Pigmentation is a rare event in benign and malignant adnexal tumors, and to our knowledge, no similar case has been reported.

Argyrophilic nucleolar organizer regions of thyroid lesions on fi ne needle aspiration smears

Background: Argyrophilic nucleolar organizer region is higher in malignant nuclei as compared to reactive and benign nuclei. The main objective of this study was to evaluate the role of Argyrophilic nucleolar organizer region and its extent in differentiating benign and malignant lesions, particularly with respect to follicular neoplasms of the thyroid. Materials and Methods: This was a prospective, cross sectional study which included 110 patients presenting with thyroid swelling. The fi ne needle aspiration smears were studied by conventional methods and silver staining for Argyrophilic nucleolar organizer region. In 50 cases, diagnosis was confi rmed by histopathology. The Argyrophilic nucleolar organizer region count was done and the mean Argyrophilic nucleolar organizer region count per nucleus was calculated along with pattern of distribution. Results: Mean Argyrophilic nucleolar organizer region count was higher in neoplastic as compared to non-neoplastic and infl ammatory lesions. Papillary carcinoma had the highest mean Argyrophilic nucleolar organizer region count (5.40 ± 0.86) and the lowest count was seen in Hashimoto’s thyroiditis (2.10 ± 0.36). Higher mean Argyrophilic nucleolar organizer region count was recorded in follicular carcinoma (4.84 ± 1.42) as compared to follicular adenoma (3.5 ± 0.27) which was found to be statistically signifi cant (P<0.05). Argyrophilic nucleolar organizer region dots were arranged in clusters in colloid goiter whereas scattered discrete black dots were seen in neoplastic lesions. Conclusion: Argyrophilic nucleolar organizer region study of thyroid can be used as an additional diagnostic adjunct with cytomorphological features to differentiate benign and malignant follicular neoplasms. Journal of Pathology of Nepal (2013) Vol. 3, No.1, Issue 5, 361-366 DOI: http://dx.doi.org/10.3126/jpn.v3i5.7859

Occurrence of trichoepithelioma in a cat: Histopathologic and immunohistochemical study

Trichoepitheliomas are benign follicular appendage tumors with differentiation to all three segments of the hair follicle. A 2 years old female domestic short hair cat presented with a mass on the tail. The mass was surgically excised and for histopathologic and immunohistochemical studies, was sent to Department of Pathology. Histologically, the tumor was encapsulated and consisted of many islands of follicular epithelium and also cysts structures which varied in size and shape. The cells of epithelium islands were round to oval and had variable amounts of slightly, eosinophilic cytoplasm and euchromatic nuclei. The cystic structures were lined by a complex layer of squamous epithelium. Often, cells under went an abrupt transition between basal layers and keratinization without the development of a granular cell layer. No tendency of malignancy was seen in this case. According to mentioned characteristics, trichoepithelioma was diagnosed. By immunohistochemical study it was confirmed that this tumor had epithelial origin because squamous tumor cells reacted with the pan-cytokeratin antibody. The expression of β-catenin was predominately cytoplasmic and also together with numerous positive nuclei but membranous expression was inconsistenet. Distribution of neoplastic cells with β-catenin expression was more than 75% and labeling intensity was strong in both cytoplasm and nuclei. According to author's knowledge, this is the first report of trichoepithelioma in cat in Iran and also investigation of β-catenin expression in feline trichoepithelioma in veterinary literature.

Metastases of Renal Cell Carcinoma to the Thyroid Gland with Synchronous Benign and Malignant Follicular Cell-Derived Neoplasms

Clear cell renal cell carcinoma (CCRCC) is the most common origin for metastasis in the thyroid. A 51-year-old woman was referred to our hospital for a subcarinal lesion. Ten years before, the patient had undergone a nephrectomy for CCRCC. Whole-body fluorodeoxyglucose positron emission tomography revealed elevated values in the thyroid gland, while the mediastinum was normal. An endoscopic ultrasonography-guided fine-needle aspiration biopsy of the mediastinal mass was consistent with CCRCC, and this was confirmed after resection. The thyroidectomy specimen also revealed lymphocytic thyroiditis, nodular hyperplasia, one follicular adenoma, two papillary microcarcinomas, and six foci of metastatic CCRCC involving both thyroid lobes. Curiously two of the six metastatic foci were located inside two adenomatoid nodules (tumor-in-tumor). The metastatic cells were positive for cytokeratins, CD10, epidermal growth factor receptor, and vascular endothelial growth factor receptor 2. No BRAF gene mutations were found in any of the primary and metastatic lesions. The patient was treated with sunitinib and finally died due to CCRCC distant metastases 6 years after the thyroidectomy. In CCRCC patients, a particularly prolonged survival rate may be achieved with the appropriate therapy, in contrast to the ominous prognosis typically found in patients with thyroid metastases from other origins.

Desmoplastic trichoepithelioma with perineural involvement: a series of seven cases

Desmoplastic trichoepithelioma (DTE) is a benign follicular tumor occurring most commonly within facial skin of young and middle-aged women, morphologically characterized by a superficial dermal proliferation of basaloid cells growing in narrow strands embedded in a desmoplastic stroma associated with small keratinizing cysts. DTE must be distinguished from other benign epithelial proliferations such as syringoma, microcystic adnexal carcinoma and infiltrating basal cell carcinoma. Among morphological features useful in that distinction, perineural involvement is considered a feature indicative of malignancy. We present a series of seven DTEs with otherwise typical presentation and morphology, nevertheless showing epithelium present in the perineural spaces of adjacent small dermal nerves. Patients ranged in age from 14 to 66 years (mean 44 years). All seven tumors were restricted to dermis, showed strands of basaloid epithelium in desmoplastic stroma and contained CK20-positive cells. Additionally, five of five examined tumors displayed diffuse expression of p75 neurotrophin receptor. Five patients were followed up clinically (follow-up time range: 2 months-4 years). No tumor recurrence was observed in any of these patients. We postulate that perineural involvement is an unusual feature of DTE that should not be equated with malignancy or lead to unnecessary over-treatment.

Familial multiple pilomatrixomas as a presentation of attenuated adenomatosis polyposis coli

Pilomatrixomas are benign follicular tumors that occur most commonly in children. Rare multiple or familial pilomatrixomas have been associated with myotonic dystrophy and other disorders. Although sporadic pilomatrixomas and hybrid cutaneous cysts with pilomatrixoma-like features have been observed in some kindreds with Gardner syndrome, an autosomal dominant form of familial adenomatous polyposis, no definitive association has been made with multiple or familial pilomatrixomas. Here we describe two siblings with multiple pilomatrixomas who were also found to have a family history of colonic adenocarcinoma. Genetic testing revealed a mutation in the 5' portion of the adenomatous polyposis coli (APC) gene, in a region associated with an attenuated APC phenotype. These findings show that multiple pilomatrixomas may be the presenting symptom of patients with APC gene mutations.

Preoperative serum thyroglobulin concentration is an independent predictive factor of malignancy in follicular neoplasms of the thyroid gland

A distinction between a benign follicular neoplasm (FN) and a malignant FN based entirely on cytologic examination of fine-needle aspiration biopsy is not possible. The aim of this retrospective study was to find predictive factors of carcinoma in patients with FN. A chart review of 388 patients (314 females, 74 males; mean age 50 years, range 9-81 years) with FN, who were surgically treated between 1988 and 2009, was performed. Predictive factors for malignancy were identified by the chi-squared test and multivariate logistic regression. The histopathological diagnoses were carcinoma, adenoma, and benign goiter in 127 (33%), 126 (32%), and 135 (35%) patients, respectively. The independent predictors of malignancy as shown by multivariate logistic regression were age of patients (OR 1.88, P = 0.008), solitary tumor (OR 1.72, P = 0.037), and Tg concentration (OR 2.36, P = 0.001). Carcinoma was more common in patients younger than 45 years, with solitary tumor and with preoperative serum Tg concentration more than 400 ng/ml. The independent predictors of malignancy in FN were age of patients, solitary tumor, and preoperative Tg concentration. The determination of Tg concentration may be useful in the patients with FN in order to decrease the number of completion thyroidectomies.

Approach to the Patient with Nontoxic Multinodular Goiter

Thyroid nodules are very common, and although the majority are benign, approximately 5% may harbor malignancy. The evaluation of the patient with solitary thyroid nodule is generally straightforward and will typically include measurement of serum TSH to assess thyroid function and fine-needle aspiration biopsy of the nodule, with or without ultrasound (US) guidance. The approach to the patient with nontoxic multinodular goiter represents a more difficult problem for the clinician. All patients should have serum TSH measured to assess functional thyroid status and US examination to evaluate the number, size, and sonographic features of the nodules and assist in the selection of nodules that may need fine-needle aspiration biopsy. Patients with nodules yielding malignant cytology should be referred for surgery. Given the lack of reliable markers to predict biological behavior of nodules with suspicious (indeterminate) cytology, patients with such nodules are generally advised to have surgery, unless autonomous function of these nodules can be confirmed by scintigraphy. Most of these patients, however, will ultimately prove to have benign follicular tumors. Many patients with benign but large goiters may experience clinical symptoms of pressure, such as dysphagia, choking sensation, or airway obstruction. Such patients will often require surgery for alleviation of symptoms. In the absence of malignancy, asymptomatic patients may be observed. Radioactive iodine, commonly used in many parts of Europe, is safe and effective and may be a reasonable option for many patients. Periodic follow-up with neck palpation and US exam is recommended for all patients.

Characteristic ultrasonographic features of the encapsulated papillary thyroid carcinoma

To evaluate the ultrasound (US) features of the encapsulated papillary thyroid carcinoma (EPTC). Based on ultrasonographic features including shape, size, border, echogenicity, hypoechoic halo and microcalcification, 33 cases of EPTC were classified into two groups: 21 cases in irregular shape group and 12 cases in spherical or oval shape group. EPTC in the irregular shape group showed some ultrasonographic features including jagged border, irregular tumor shape and marked hypoechogenicity, while the ultrasonographic features of EPTC in the spherical or oval shape group included smooth border, regular shape, isoechogenicity and hypoechoic halo. Hypoechoic halo and isoechogenicity were found more frequently in EPTC of spherical or oval shape group than those in EPTC of irregular shape group. The size of EPTC in the spherical or oval group was commonly larger than that of EPTC in the irregular shape group. The findings indicate that EPTC have some ultrasonographic features similar to benign follicular thyroid tumors.

Composite tumors associating trichoblastoma and benign epidermal/follicular neoplasm: another proof of the follicular nature of inverted follicular keratosis

Trichoblastomas (TBs) are benign follicular tumors that can present either as solitary nodule or as multiple facial papules. Only one case of sporadic TB in a composite tumor has been reported, arising in an apocrine poroma. We report the association of TB and benign epidermal/follicular neoplasm in six patients. Clinical data available were collected. Serial sections and immunohistochemical (IHC) analysis for CK17 and human papilloma virus (HPV) were performed on available materials. Five of the six patients were males. Mean age at diagnostic was 56 years. Lesions were localized on the face and scalp in four of six patients. The lesions associated with TB were inverted follicular keratosis (IFK) in three cases, seborrhoeic keratosis (SK) in two cases and IFK with verruca vulgaris pattern in one case. IHC for HPV was negative in the four cases tested. Staining for CK17 was always positive in TB. It was often positive in the associated neoplasm. TB can be associated with benign epidermal/follicular neoplasm in composite tumors. The association of TB and IFK with direct connection between the lesions is another argument in favor of the follicular origin of IFK. TB can be added to the spectrum of SK-associated tumors. Battistella M, Peltre B, Cribier B. Composite tumors associating trichoblastoma and benign epidermal/follicular neoplasm: another proof of the follicular nature of inverted follicular keratosis.

Panfolliculoma: report of two cases

Panfolliculoma is a distinctive and unusual benign follicular neoplasm. It shows differentiation towards all components of the hair follicle, including the upper and the lower segments. We report two cases of this rare disease. The first patient presented with a painful nodule on the scalp and the second patient had an asymptomatic skin-colored nodule on his left eyebrow. Histopathologic examination of both cases revealed lobular proliferation of solid-cystic follicular structures. The cystic structures contain laminated keratin, indicating infundibular differentiation. The solid tumor part was composed of basaloid germinative cells, matricial cells, and cells with trichohyalin granules, representing inner root sheath differentiation. The range of differentiations was highlighted using immunohistochemical stains, including labeling of cytokeratin 1, 5, 10, 14 (using 34bE12), cytokeratin 5/6, CD34 (outer root sheath), and Ber-EP4 (lower segment of hair follicle). Panfolliculoma should not be confused with trichofolliculoma or trichoblastoma.

Microcystic adnexal carcinoma – aggressive infiltrative tumor often with innocent clinical appearance

Microcystic adnexal carcinoma is a rare sweat gland malignancy, characterized by slow, but aggressive infiltrative growth. Histologic characteristics are follicular and glandular differentiation, as well as bland cytologic features. The benign histologic appearance, particularly in the upper level of the tumor, can be confused with syringoma or benign follicular neoplasm. Thus the risk of misdiagnosis is considerable, especially if only superficial biopsies are provided. We report two patients with microcystic adnexal carcinoma, using them as a basis to discuss, pathogenesis, diagnosis, histology and therapy of the tumor.

Trichoadenoma of Nikolowski is a distinct neoplasm within the spectrum of follicular tumors

Trichoadenoma is a rare benign follicular tumor first described by Nikolowski 50 years ago. Both trichoadenoma and desmoplastic trichoepithelioma are composed of cords of epithelial cells and cornifying cysts embedded in sclerotic stroma. In trichoadenoma the cystic component predominates, while desmoplastic trichoepithelioma is a mostly solid neoplasm. Therefore trichoadenoma was suggested to represent a cystic variant of desmoplastic trichoepithelioma. The aim of this study was to investigate whether the morphologic overlap between trichoadenoma and desmoplastic trichoepithelioma translates into a similar immunohistochemical profile. We studied 19 trichoadenomas and 21 desmoplastic trichoepitheliomas for cytokeratin 20, Ber-EP4, and androgen receptor expression. Eighteen of 19 trichoadenomas and all desmoplastic trichoepitheliomas demonstrated the presence of Merkel cells as detected by a monoclonal antibody against cytokeratin 20. In contrast, while all desmoplastic trichepitheliomas were positive for Ber-EP4, only 4 of 19 trichoadenomas showed any kind of reactivity for this marker. None of the trichoadenomas or desmoplastic trichoepitheliomas expressed androgen receptor. This study is limited by the moderate number of these rare tumors available for immunohistochemical analysis. Our data demonstrate that trichoadenoma typically retains cytokeratin 20-positive Merkel cells but lacks Ber-EP4 and androgen receptor expression. Trichoadenoma is a distinct follicular tumor related but not identical to desmoplastic trichoepithelioma.

The Immunohistochemical Patterns of the β-Catenin Expression in Pilomatricoma

Pilomatricoma is a benign follicular tumor that is composed of basaloid cells, transitional cells and shadow cells. beta-Catenin is a 92-kDa protein, and it plays important roles in cell-cell adhesion at the cell membrane and signal transduction in the nucleus. beta-Catenin has recently been shown to play an important role in the formation of hair follicle-related tumors, including pilomatricoma. However, the pattern and the intracellular localization of the beta-Catenin expression are still controversial. We wanted to evaluate the pattern and the intracellular localization of the beta-Catenin expression in pilomatricoma by performing immunohistochemical staining. Twenty-seven paraffin-embedded tissue samples that were diagnosed as pilomatricoma were immunohistochemically stained with beta-Catenin antibody. Basaloid cells were found 15 samples of the total 27 pilomatricomas. All (15/15) of the basaloid cells strongly expressed beta-Catenin, but the transitional cells and the shadow cells did not. In the basaloid cells, the nuclei and membranes showed prominent beta-Catenin immunoreactivities, but the cytoplasm showed weak beta-Catenin immunoreactivity. This study confirmed that the nucleus and membrane of all the basaloid cells in the pilomatricomas showed a strong beta-Catenin expression, but the transitional cells and shadow cells showed negative beta-Catenin immunoreactivity.

Infundibulomatosis: A case report with immunohistochemical study and literature review

Tumor of the follicular infundibulum was first described in 1961 by Mehregan and Butler in a patient presenting with multiple papules. It is more frequent, however, as an isolated lesion affecting mainly the face, neck, and upper trunk. Clinical presentation is variable, requiring histology for the diagnosis, which reveals typically a plate-like proliferation of keratinocytes in continuity with the epidermis and hair follicles; some morphological features are reminiscent of the outer root sheath of the hair follicle. A well defined network of elastic fibers surrounding the tumor is usually present using the appropriate staining and this finding is specific because it is not found in other benign follicular tumors. Multiple infundibulomas are usually sporadic and there is no apparent association with internal malignancy. The authors report the case of a 30-year-old female patient with a 5-year history of multiple small discrete hypopigmented macules and papules, scattered over the submental and submaxillary regions and anterior neck. Histopathological findings were consistent with the diagnosis of tumor of the follicular infundibulum. Immunohistochemical study was performed to further characterize the proliferation.

Expression of Vascular Endothelial Growth Factor and Presence of Angiovascular Cells in Tissues from Different Thyroid Disorders

Vascular endothelial growth factor (VEGF) is involved in tumor angiogenesis and other pathophysiological processes. We studied the localization of VEGF in human thyroid tissues to clarify its involvement in proliferative processes in a variety of thyroid disorders. Immunohistochemical analysis using purified rabbit polyclonal anti-human VEGF or anti-human CD34 antibody and a streptavidin-biotin peroxidase complex detection system was performed on 58 tissue specimens from 53 patients with different thyroid disorders and 5 normal thyroid glands. Vascular endothelial growth factor was not detected in normal thyroid follicular cells. However, some thyroid tumor cells expressed VEGF in the cytoplasm (papillary carcinoma, 10/18; follicular carcinoma, 1/3; medullary carcinoma, 2/2; follicular adenoma, 3/11; adenomatous goiter, 2/4). In benign follicular adenoma and adenomatous goiter, weak expression of VEGF was found in small areas of the tumor, whereas in malignant thyroid tumors, it was strongly expressed in many cells. However, VEGF was not expressed in anaplastic carcinoma, malignant lymphoma, or Graves' disease. Angiovascular cells stained with CD34 antibody in tissues from different thyroid disorders reflected statistically significant differences in papillary carcinoma, follicular adenoma, and Graves' disease compared with normal thyroids, and such cells showed a trend toward increases in medullary carcinoma and adenomatous goiter. In contrast, low vascularity was observed in anaplastic carcinoma, malignant lymphoma, and follicular carcinoma. Because VEGF probably functions as a hypoxia-inducible angiogenic factor, overexpression of this mediator, concomitant with hypervascularity, may be induced more strongly in malignant thyroid tumors, which need more oxygen to proliferate, than in benign follicular tumors. However, neither VEGF nor CD34 was expressed in anaplastic thyroid carcinoma, which is an extremely poorly differentiated malignant tumor. CD34 but not VEGF was expressed in the hyperplastic thyroid tissues of Graves' disease composed of nontransformed cells. Thus, the expression of VEGF concomitant with CD34 is suggested to reflect both the transformation and differentiation state of malignant tumors.

Trichogerminoma

A case of distinctive benign follicular neoplasm previously reported under the designation of trichogerminoma is described. A 45-year-old man presented with an asymptomatic nodule on the scalp since 3 years. Histologically, the lesion corresponded to a well-organized, symmetrical dermal nodule made up of basophilic lobules included in a fibrocytic stroma. The lesion had the characteristics of hair germ tumors; however, most lobules depicted a distinctive pattern of rounded nests of concentrically arranged clear cells. Small follicle bulb-like basophilic structures, foci of sebaceous differentiation, and areas of infundibulocystic, isthmic, and outer sheath keratinization were also seen. This neoplasm and the other tumors with hair germ differentiation such as trichoblastoma and panfolliculoma seem to represent the same spectrum of hair follicle neoplasms only distinguishable by their degree of differentiation.

甲状腺内視鏡下手術―鎖骨窩法１０例の経験と吊り上げ式腋窩アプローチ法の試み―

From July 2006 to October 2007, we performed video-assisted neck surgery (VANS) via a subclavicular approach in 10 patients with thyroid tumor. Seven had benign follicular tumor, and three had papillary carcinoma. All cases underwent hemithyroidectomy. One case of papillary carcinoma underwent additional central neck dissection (D1). The mean operating time was 207 min, and the mean blood loss was 70 ml. Transient recurrent laryngeal nerve palsy was noted. However, postoperative bleeding was not observed. To improve the esthetic outcome, we applied a new method: a skin lifting axillary approach. We applied this method to a 27-year-old female patient with benign follicular tumor showing no postoperative complications. The axillary scar was not visible when the ipsilateral arm was in its natural position. This new method is a feasible procedure with esthetic benefits, and may offer a practical alternative for patients requiring sugical removal of the thyroid gland.

Bcl‐2, CD34 and CD10 expression in basaloid follicular hamartoma, vellus hair hamartoma and neurofollicular hamartoma demonstrate full follicular differentiation

Generalized basaloid follicular hamartoma syndrome (GBFHS) is a rare, recently-described, autosomal-dominantly inherited disorder that presents with disseminated milia, palmoplantar pitting, hypotrichosis and basaloid follicular hamartomas (BFH). BFH is a benign adnexal tumor that resembles basal cell carcinoma (BCC). In this study, we report two cases of GBFHS and stain BFH, a vellus hair hamartoma (VHH) and a neurofollicular hamartoma (NH) with CD34, bcl-2 and CD10 to characterize and compare the staining patterns of these follicular tumors. Standard immunohistochemistry labeling with CD34, bcl-2 and CD10 was performed on paraffin-embedded, formalin-fixed tissue sections of five BFH (four for CD10), one VHH and one NH. CD34 stromal staining was observed in all specimens. Bcl-2 stained the outermost cell layers of the basaloid nests in all specimens. CD10 stained the peritumoral stroma of all specimens. The BFH, NFH and the VHH showed CD10 staining of matrical cells. CD34 and CD10 stain peritumoral stroma of BFH, VHH and NH. Bcl-2 stains the outermost cell layer of these tumors. CD10 was also observed to stain matrical cells. These results show the similarities in differentiation between these benign follicular neoplasms and trichoepithelioma.