Reappraisal of the Confusing Concept “Trichogerminoma” and the Ill-Defined Finding “Cell Balls”: Clinicopathologic Analysis of 6 Cases of Trichogerminoma and Comparison With 2 Cases of Basal Cell Carcinoma With Cell Ball–Like Featuresписьмо
Аннотация: To the Editor: Trichogerminoma is a follicular germinative cell tumor, histopathologically characterized by the formation of cell balls, which are composed of pale cells or pale eosinophilic cells in the center and germinative basaloid cells in the periphery. Although trichogerminoma was first proposed in 1992,1 there is still no consensus regarding its diagnostic features. A thorough review of the literature published between October 1992 and October 2016 revealed a total of 24 trichogerminoma cases published in 10 reports.1–10 However, the authors consider that 2 of these 24 cases had histopathologic features suggestive of pilomatricoma or pilomatrical carcinoma.4,8 Additionally, 1 patient (case 13) in the first report exhibited the characteristics of small nodular-type basal cell carcinoma or trichoblastoma.1 The authors also doubt whether another patient (case 12) in the first article, who exhibited an aggressive clinical course, was indeed a trichogerminoma.1 Moreover, some textbooks demonstrate histopathologic figures of trichogerminoma11–17; however, they include uncertain cases with no recognizable cell balls11,15,16 and typical cases of trichogerminoma presented as conventional trichoblastoma.13,14,17 Epperson and Libow18 reported an interesting case of trichogerminoma with pilomatrical differentiation. However, before the diagnosis of trichogerminoma is established, it is necessary to rule out the possibilities of other follicular tumors, including panfolliculoma and pilomatricoma with prominent small nodular formation. There are a few reasons why trichogerminoma might not be the appropriate diagnosis in this case. First, trichogerminoma typically presents as several cell balls within a large tumor nest or several cell balls connected to each other with epithelial bridging.1–3,5–7,9,10 However, the case by Epperson et al exhibits an individual distribution of nodules, each of which is separated by surrounding stroma. The nodular structures in this case would be indistinguishable from those in other follicular tumors, including small nodular-type trichoblastoma. Second, the centers of cell balls in trichogerminoma are composed of pale cells or pale eosinophilic cells with a vaguely concentric arrangement.1–3,5–7,9,10 In contrast, the centers of the nodules for the case by Epperson and Libow18 were composed of bright eosinophilic cells with no concentric arrangement. The bright eosinophilic cells in the spherical structures could represent an ischemic change or a differentiation toward inner root sheath and are considered to be different from those in the cell balls of trichogerminoma. Third, the histomorphological and immunohistochemical findings of this case are compatible with those of panfolliculoma or pilomatricoma, although the marked nodular formation is unusual for pilomatricoma and for trichogerminoma. Cytokeratin (CK) 7 can be focally positive in panfolliculomas and pilomatricomas (our unpublished observations). The present study analyzed 6 cases of trichogerminoma and 2 cases of basal cell carcinoma with cell ball–like features (including small nodular type, and cystic and small nodular type). Two of the trichogerminoma cases and 1 of the basal cell carcinoma case were also studied using immunostaining. For the 6 patients with trichogerminoma, the median age was 65 years (34–88 years) and the sex ratio (male:female) was 3:3. The tumor locations were forehead (2), scalp (1), low back (1), forearm (1), and thigh (1) (Fig. 1A). For 5 cases, the tumors were localized from the dermis to the subcutis, and for 1 case, the tumor was present only in the dermis. The median size was 9 mm (3–27 mm). Histopathologically, the cell balls in all cases of trichogerminoma were distributed in large tumor nests or connected to each other via epithelial strands, but not as individual nodules separated by surrounding stroma (Figs. 1B–D). One case (17%) showed a connection to the overlying epidermis. One case (17%) contained melanin pigments in the tumor (Fig. 1B). Two cases (33%) showed focal sebaceous differentiation, and no case (0%) showed pilomatrical differentiation. All cases (100%) of trichogerminoma partially contained the components of conventional trichoblastoma that revealed no features of cell balls (Fig. 1B). The conventional trichoblastoma components occupied 70% (30%–90%) of the whole tumor areas. All cases (100%) show a concentric fibroblast-rich stroma with variable condensation but no retraction clefts between the tumor nests and stroma. Immunohistochemistry for 2 cases of trichogerminoma revealed that CK5/6 was expressed wholly in both, the cell balls and other areas of the tumor, and that zonal CK5/6 immunostaining in cell balls (CK5/6 negativity for the centers of the cell balls) was observed only in the very focal area of the tumor in one case (Fig. 1E). GATA319 and p4020 were diffusely positive in 2 cases, including within the cell balls. Several CK20-positive Merkel cells were scattered in the tumor nests of 2 cases but never in the cell balls (Fig. 1F). Immunoreactivity for CD117 (c-KIT), which is usually negative for follicular tumors,21 was observed in the tumor nests of extra-ball areas. The tumor cells were diffusely positive for β-catenin showing a membranous pattern. In contrast, basal cell carcinomas with cell ball–like features showed individual nodules separated by the surrounding stroma (Fig. 2A). The centers of the cell ball–like elements were composed of non-pale eosinophilic cells (Fig. 2B). The immunoprofile of the cell ball–like round nodules for CK5/6, GATA3, p40, and β-catenin was the same as that of the cell balls in trichogerminomas. CK20-positive cells and CD117 immunoreactivity were absent in the case of basal cell carcinoma, which might be useful to distinguish it from trichogerminoma.FIGURE 1.: Clinical, histopathologic, and immunohistochemical features of trichogerminomas. A, A dome-shaped nodule with a smooth surface of normal skin color and focal telangiectasia is clinically observed in a case of a 9-mm-sized nodule on the forehead. B, Histopathologically, the tumor of another case contains a conventional trichoblastoma component (black arrows) with melanin pigments and a trichogerminoma component (red arrows) that shows several cell balls packed into large tumor nests. C, The cell balls containing pale cells in the centers are connected to each other with epithelial bridging. D, The pale pink cells can also be observed in the centers of the cell balls. E, CK5/6 is diffusely positive in cell balls but more weakly stained in the central part of only a few cell balls of one case (black arrows). F, CK20-positive Merkel cells are scattered in the tumor nests of extra-ball areas. Images were obtained using ×2 (B), ×10 (D and F), or ×20 (C and E) objectives.FIGURE 2.: Histopathologic features of basal cell carcinomas with cell ball–like structures. A, Basal cell carcinoma of the small nodular type could exhibit cell ball–like nodular structures, separated individually by the surrounding stroma. B, The high-power findings of each nodule are similar to those of cell balls in trichogerminoma, but the cytoplasm of the center component cells is more eosinophilic and distinguishable from that in trichogerminoma. Images were obtained using ×1 (A) or ×12.5 (B) objectives.In summary, each of the cell balls in trichogerminoma shows histopathologic features similar to that of the round structures in small nodular-type basal cell carcinoma; however, the distribution pattern of cell balls and the cytoplasmic composition of the center component cells in trichogerminoma are different from those of small nodular-type basal cell carcinoma. Thus, the cell balls in trichogerminoma should be strictly defined as several nodules packed into large tumor nests or connected to each other by epithelial bridging, in which nodules show a concentric arrangement of pale cells or pale eosinophilic cells in the centers. Without such a strict definition, small nodular-type trichoblastomas and small nodular-type basal cell carcinomas and other follicular tumors with nodular formation could be admixed into the category of trichogerminomas. However, the present study also revealed that trichogerminoma has no specific clinical features distinguishable from conventional trichoblastoma. In addition, all 6 cases of trichogerminoma, indeed, partially exhibited the conventional component of trichoblastoma. Therefore, trichogerminoma cannot be a distinct entity but is rather a microscopic variant of trichoblastoma—just like cutaneous lymphadenoma and trichoblastic fibroma—or a pattern of trichoblastoma.
Год издания: 2017
Авторы: Keisuke Goto, Toshihiro Takai, Takashi Anan, Tetsunori Kimura, Takaya Fukumoto, Hironobu Murai, Nao Nishitani, Toshiaki Sato
Издательство: Lippincott Williams & Wilkins
Источник: American Journal of Dermatopathology
Ключевые слова: Cancer and Skin Lesions, Tumors and Oncological Cases, Histiocytic Disorders and Treatments
Другие ссылки: American Journal of Dermatopathology (HTML)
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Открытый доступ: bronze
Том: 40
Выпуск: 7
Страницы: 543–546