Giant polypoid basal cell carcinoma with features of fibroepithelioma of Pinkus and extensive cornification

ARTICLE

Auteur(s) : Noriyuki MISAGO, Yasuyuki SUZUKI, Yoshihiro MIURA, Yutaka NARISAWA

Division of Dermatology, Department of Internal Medicine, Faculty of Medicine, Saga University, Nabeshima 5-1-1, Saga 849-8501, Japan

Article accepted on 16/02/2004

Basal cell carcinoma (BCC) that occurs on the genital region, including the pubic and perianal areas, is rare with a frequency ranging from 0.2 to 0.3% [1, 2]. The clinical and histopathological features of BCCs on the genital regions exhibit heterogeneity and are similar to those found in other anatomic areas; i.e., the common nodular type of BCC [1, 2]. Favorable sites for lesions for fibroepithelioma of Pinkus, a rare type of BCC with an approximate frequency from 0.3 to 1.4% [3, 4], include the lumbosacral region and the genital or groin areas [3, 5, 6]. Fibroepithelioma of Pinkus frequently has a clinical appearance of polypoid lesions [3, 4], however, it rarely develops into a giant-sized lesion. We present here a giant polypoid lesion that manifested as fibroepithelioma of Pinkus with cornification that merged with a nodular BCC that had extensive cornification and exhibited the so-called histopathological keratotic BCC.

Case report

A 61-year-old woman with a genital lesion was unaware of its initial presence and thus the exact duration of the lesion was not clear. During the year prior to her visit to our office, the lesion gradually grew to become a large tumor. Examination revealed a partly ulcerated and crusted, flesh-colored, polypoid tumor, measuring 7.1 × 5.0 × 2.2 cm with a relatively broad pedunculated base, which was mainly located on the left side of the pubis and partly extended to the left labia majora (Fig. 1A, B). A pigmented, waxy, 1.1 × 0.8 cm-sized, small nodular lesion was juxtaposed with the right side of the polypoid tumor. No palpable lymph nodes were noted on the groin. Radiological and laboratory examinations disclosed no abnormalities. The lesion was completely excised to the fascia, and a pedicle graft was applied. Neither recurrence nor metastasis has been observed during the three years of follow-up.
Histopathologically, scanning magnification of the combined two slides (two halves of the specimen cut in half), revealed an asymmetrical, polypoid and exophytic neoplasm in the dermis that was composed of basaloid aggregations varying in size and shape (Fig. 2A). The basaloid aggregations were restricted primarily to the polypoid area. Most of the aggregations showed peripheral palisading and mucinous retraction spaces. Notably, the compact, cornified contents with a whorled appearance were observed within considerable numbers of the aggregations (Fig 2B). The cornified areas were sometimes associated with parakeratosis and about half of the cornified areas showed keratohyaline granules in the lining cells of the cornified contents. These histopathologic features were in accordance with those of nodular BCC with extensive cornification, the so-called keratotic BCC. A pigmented and waxy nodular lesion revealed to be a small and conventional nodular BCC.
Characteristically, considerable portions of the superficial part of this giant, polypoid BCC showed characteristic features of fibroepithelioma of Pinkus with columns and cords of neoplastic, basaloid aggregations that were continuous with the surface epidermis and formed a fenestrated pattern (Fig. 3A). Thicker and more irregular neoplastic columns and cords without a fenestrated pattern other than conventional fibroepithelioma of Pinkus were also observed. The columnar basaloid cells were aligned in palisades at the periphery of the aggregations and primitive germ-like structures protruded from the aggregations. The stroma was highly fibrocytic and a continuous, rudimentary follicular papilla was occasionally observed (Fig. 3B). In addition to the mucinous retraction spaces, clefts were also observed between the fibrocytic stroma and adjacent normal dermis. Another characteristic feature was the frequent cornification, indicated by compact, eosinophilic and homogenous cornified contents within the aggregations (Fig. 3c).
Immunohistochemistry was performed on the deparaffinized sections in this case in order to briefly investigate the immunohistochemical expression patterns of anticytokeratin (CK) in the cornified areas and the distribution of Merkel cells in this BCC using the avidin-biotin method with an alkaline phosphatase detection system according to the manufacturer’s instructions. The following antibodies against CKs were used, both at their recommended dilution and at a higher concentration than recommended by the manufacturer: CK1 (34 β B4, Enzo), CK10 (DE-K10, Dako), CK17 (E3, Dako), CK20 (IT-Ks 20.8, Progen). CK20 was used as a marker for Merkel cells. CKs 1 and 10 were positive in the surrounding cells in about 60% of the cornified areas, and CK10 was positive in the cornified contents in 30% of the cornified areas (Fig. 4a). CK17 was positive in the surrounding cells in all of the cornified areas and positive for the cornified contents in about 60% of the cornified areas (Fig. 4b). In the epidermis overlying the giant, polypoid BCC, several Merkel cells located in the basal epidermis especially in epidermal nubbins or cords (Fig. 4c). Only a few Merkel cells were scattered within the neoplastic aggregations in the fibroepithelioma of Pinkus part (Fig. 4d), and no Merkel cells were observed within the aggregations in the nodular (keratotic) BCC part.

Discussion

Giant BCC is generally defined as a lesion greater than 5 cm at its greatest diameter [7, 8]. The clinical forms of the giant BCC include exophytic (vegetant) [8-14], noduloulcerative [15], morpheaform [7], and extensively ulcerative [16-20]. The exophytic BCCs often show the polypoid appearance [9, 11, 13]. The histopathological types of giant BCCs have been reported to frequently be aggressive ones (such as morpheaform or micronodular type) as well as of the nodular and infiltrative types [7, 17]. The giant BCC, which histopathologically demonstrates fibroepithelioma of Pinkus merging with a nodular (keratotic) type, is highly exceptional. Only one case similar to our patient was reported in 1966 [21]. Using the term giant premalignant fibroepithelioma, the case reported a plaque-like elevated lesion of a 15-year duration that was located on the lower abdominal wall of a 76-year-old man, and measured 7.5 × 6.5 × 1.0 cm [21]. Histopathologically the lesion exhibited fibroepithelioma of Pinkus in continuity with a nodular type BCC like the present case [21].
Giant BCCs greater than 10 cm and with long duration and aggressive histopathological types have been suggested to often have a high mortality representing fatal and metastatic BCCs [16, 17]. However, exophytic or polypoid giant BCCs that do not invade deeply into the subcutaneous tissue and muscle and those with non-aggressive histopathological types, like the one presented here, are considered not to have a high mortality rate.
Contributing factors to the size in giant BCC are considered to be neglect and inadequate treatment of the primary lesion [22-24]. Although some reports have suggested that giant BCCs exhibit similar anatomical locations to those in conventional BCCs (that mostly occur on the head and neck) [7, 15] other reports have observed that giant BCCs are mainly located on the trunk, where the lesions are easily hidden; producing neglect in reclusive patients [8]. One clinical report [2] suggested that the average size of 51 genital and perianal BCCs at the time of presentation could be classified as large: 1.95 cm (range, 0.5-5.2 cm), probably due to the delay in diagnosis (due to unawareness by both patients and physicians), and occasionally reports of giant, genital BCC have been seen [18-20]. In this particular patient with giant, genital BCC, the unawareness, hesitation to visit to the clinic as well as neglect factors seem to be the contributing reasons for the overall size of the lesion.
In rare instances, BCC, which would be a trichoblastic carcinoma, histopathologically exhibits distinct follicular differentiation [25, 26]. Fibroepithelioma of Pinkus is a typical example of BCC with limited follicular differentiation representing follicular germ-like structures and sometimes exhibits follicular germs and rudimentary follicular papilla that are observed all along the columns of the basaloid aggregations (continuous germ and papilla) [25, 26]. Fibroepithelioma of Pinkus may episodically show more advanced follicular differentiation in the form of discrete follicular bulbs and papillae, and cornification in fibroepithelioma of Pinkus observed in the present case seems to be a rare event [25, 26].
The concept of so-called keratotic BCC is obscure and not well defined [27]. The cornified areas observed in both the fibroepithelioma of Pinkus and keratotic BCC parts in the present case, showed compact, eosinophilic and homogenous cornified contents often with a whorled appearance, and the cornified contents in about 60% of the cornified areas were positive for CK17; demonstrating the form of cornification in the isthmus [27]. In this BCC, CKs 1 and 10 were also positive in the surrounding cells in about 60% of the cornified areas, and keratohyaline granules were seen in the surrounding cells in about half of the cornified areas; suggesting infundibular differentiation [27]. Although the BCC presented exhibited mainly outer root sheath differentiation and an attempt to cornify in the form of an isthmus, the differentiation was considered to be abnormal; resulting in concomitant infundibular differentiation.
Although fibroepithelioma of Pinkus is generally classified into a type of BCC, it has some histopathological features in common with those of retiform trichoblastoma [25, 26]. Hartschuh and Schulz [28] suggested that fibroepithelioma of Pinkus is related to benign trichoblastoma rather than BCC based on the constant occurrence of Merkel cells in fibroepithelioma of Pinkus as in trichoblastoma [29]. Cases of fibroepithelioma of Pinkus in contiguity with nodular BCCs may be typical examples to show a shift of the histopathological features from trichoblastomas to BCCs, depending on additional genetic mutations [30]. While over longer durations it can develop into giant, polypoid BCC, the fibroepithelioma of Pinkus presented is considered more and more to resemble BCC because only a few Merkel cells were seen in the fibroepithelioma of Pinkus part, which developed into a nodular, keratotic BCC. n

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