Aggressive digital papillary adenocarcinoma arising on the right great toe

ARTICLE

A 20-year-old Japanese man with aggressive digital papillary adenocarcinoma on the right great toe was presented. The tumor was comprised of multiple lobules of epithelial cells exhibiting solid areas, lacking cystic spaces. A pattern of fused back-to-back glands lined by cuboidal to low columnar epithelial cells with little evidence of papillary formations was observed. Apocrine-like decapitation secretion was not observed, and continuity of the tumor to the epidermis was evident. The neoplastic cells were immunohistochemically positive for S-100 protein, but negative for epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA) and gross cystic disease fluid protein (GCDFP). Intraluminal contents, however, showed positive reactivity with CEA and EMA. On the basis of their histologic and immunohistochemical features, the tumor was diagnosed as aggressive digital papillary adenocarcinoma.

Key words: adnexal carcinoma, eccrine carcinoma, S-100 protein, sweat gland carcinoma, digital adenocarcinoma.

Aggressive digital papillary tumor is a single painless mass that occurs over the fingers and toes or the adjacent palmoplantar areas, which shows histologically an aggressive growth pattern. Branching tubular and cystic dilated ductal structures show areas of papillary projections into the central lumina. Some lesions show cellular atypia, nuclear pleomorphism, mitotic figures, and invasion of the surrounding soft tissues indicating malignancy. Helwig [1] first described a term, aggressive digital papillary adenoma and its malignant counterpart, aggressive digital papillary adenocarcinoma, and considered that these tumors are rare sweat gland neoplasms of acral skin.

We herein describe an additional case with an aggressive digital papillary adenocarcinoma, which developed on the right great toe.

Case report

A 20-year-old Japanese male noticed an asymptomatic solitary dome-shaped skin-colored firm nodule about 5 mm in diameter on the right great toe in January 1998. The nodule gradually increased in size, and slight tenderness was associated. When the patient visited a dermatologist in September 1998, the tumor was 12 mm in diameter (Fig. 1). The lesion was excised completely with the clinical diagnosis of granuloma pyogenicum. However, since the subsequent histopathological diagnosis by a pathologist was apocrine carcinoma, a re-excision was recommended. The patient was admitted to our hospital in December 1998 and examination failed to reveal enlarged lymph nodes. He had no remarkable past personal and family histories. A second resection was made 1 cm with its safety margin and full thickness skin graft was done. The postoperative follow-up of 36 months was uneventful.

Histopathology

Histopathologically, the tumor was located in the dermis and the subcutaneous tissue as a non-encapsulated nodule. This was accompanied by downward extensions from the epidermis (Fig. 2). There was evidence of clear continuity between the tumor and the epidermis (Fig. 3). The tumor consisted of variable complexity with ducts, tubules of various sizes, and solid nests with a scanty stroma, and the fused back-to-back pattern glandular growth was evident (Fig. 4a), and some tubules were elongated (Fig. 5). The tumor cells were large and polygonal in shape with eosinophilic granular cytoplasm, showing large vesicular nuclei with prominent chromatin clumps and nucleoli. Cytologic atypia was mild, and a few mitotic cells per high power fields were identified (Fig. 4b). Some tumor cells showed clear vacuolated cytoplasm. There was an obvious adenoid and tubular patterns of proliferation. Papillary formations were few, and typical decapitation secretion was not seen (Fig. 5).

Histochemistry and immunohistochemistry

Secreted material in the neoplastic glandular lumina showed the histochemical characteristics of mucin, as evidenced by positive reactions for periodic acid-Schiff (PAS), alcian blue and colloidal iron staining. Occasional PAS-positive and diastase-resistant cytoplasmic granules were observed in tumor cells in limited areas.

Immunohistochemical staining employing a peroxidase-based detection system was performed on paraffin-embedded sections of formalin-fixed tissue with the following primary antibodies: anti-epithelial membrane antigen (EMA) (DAKO, Copenhagen, Denmark), anti-carcinoembryonic antigen (CEA) (DAKO), anti-gross cystic disease fluid protein (GCDFP-15) (Alexis Biochemicals, San Diego, CA), and anti-S-100 protein (DAKO). Tumor cells were weakly to moderately positive for S-100 protein. No detectable immunoreaction for GCDFP-15 was noted. Neoplastic cells were negative for EMA and CEA, however, intraluminal materials showed positive reactivity with CEA and EMA.

Discussion

In this case, the microscopic features of the tumor are consistent with the diagnosis of aggressive digital papillary adenocarcinoma. It is considered to differentiate towards eccrine sweat glands, rather than apocrine glands, because of the absence of typical decapitation secretion. When we first observed the histological specimen, we made a diagnosis of apocrine adenocarcinoma from the following features; (a) there were the elongated tubules, which present mainly in the apocrine tumors, (b) there were only a few papillary formations, (c) surface connection with the epidermis was present. Kao et al. studied 57 samples of aggressive digital papillary adenoma and adenocarcinoma, and 40 tumors were classified as adenoma and 17 as adenocarcinoma [2]. In the study, they found that epidermal connection of the tumor was observed in only one instance. This also led us to exclude the diagnosis of aggressive digital papillary adenocarcinoma because there was clear continuity of the tumor to the epidermis in our case.

However, Duke et al. [3] have recently studied 67 cases of aggressive digital papillary adenoma and adenocarcinoma, in which five cases had epidermal connections. Accordingly, connection of the tumor to the epidermis is now not a criterion to rule out the diagnosis of aggressive digital papillary adenocarcinoma.

In addition, papillary formations were not observed in our case. According to Duke et al. [3], the typical aggressive digital papillary tumor is multinodular, solid, and cystic with papillary projections present in the cystic spaces. The cysts are formed either by central degeneration/necrosis of solid areas or amassed eosinophilic secretory material. The presence of papillae generally corresponds to the presence of cystic spaces and is evident in 56 (84%) of the cases. The papillary projections are generally of two types: pseudo-papillae formed by heaped-up epithelium without associated fibrovascular cores in an area of central tumor degeneration and true papillae formed in areas with eosinophilic secretory material, usually with fibrovascular cores. Characteristic of all lesions was a pattern of fused back-to-back glands lined by cuboidal to low columnar epithelial cells in the solid portion of the tumors. Decapitation secretion (apocrine-type) was evident in nine cases (13%). This neoplasm sometimes shows a predominantly solid pattern, with few papillary formations. Consequently, we made a diagnosis of aggressive digital papillary adenocarcinoma with little evidence of papillary formations.

Histochemically, secreted materials appeared to be mucin, and immunohistochemically, neoplastic cells were positive for S-100 protein and negative for GCDFP-15, EMA and CEA, although intraluminal materials demonstrated positive reactivity with CEA and EMA. It was reported that tumor cells were positive for S-100 protein and that CEA were positive predominantly along luminal borders and sometimes around the nuclei in the cytoplasm in aggressive digital papillary adenomas and adenocarcinomas [2]. On the other hand, in apocrine adenocarcinoma, positive immunoreactivity for GCDFP-15 has been reported [4]. Taken together, our case is immunohisctochemically thought to be consistent with aggressive digital papillary adenocarcinoma rather than apocrine adenocarcinoma.

In the early report [2], both aggressive digital papillary adenoma and adenocarcinoma are noted to have a high rate of recurrence, but aggressive digital papillary adenocarcinoma can metastasize and result in mortality. Duke et al. [3], who were responsible for the original description of this neoplasm, have recently reconsidered their concept of benign (adenoma) and malignant (adenocarcinoma) variants of aggressive digital papillary neoplasms, and now considered all cases of this neoplasm as malignant, i.e., aggressive digital papillary adenocarcinoma. Therefore, use of the term, aggressive digital papillary adenoma should be abandoned, and these tumors should be treated as carcinomas. Metastasis occurred in 14% of reported patients, but they consider that all tumors are potentially metastatic [3]. Aggressive digital papillary adenocarcinoma recurred in 50% of patients who had not their tumors excised completely nor undertaken subsequent re-excision or amputation. This result is in contrast to 5% recurrence in patients who had adequate re-excision or amputation. Accordingly, in our case, a very careful follow-up is necessary.

Recently, Jih et al. [5] reported a case of aggressive digital papillary adenocarcinoma. Histologic evaluation of the initial biopsy demonstrated features consistent with aggressive digital papillary adenoma; however, re-excision of the remaining lesion revealed histologic features consistent with aggressive digital papillary adenocarcinoma. This case supports the idea that aggressive digital papillary tumors should be classified as aggressive digital papillary adenocarcinoma.

In Japan, there is one previous report of this tumor, in which a histochemical study was performed [6]. According to this report neoplastic cells were amylophosphorylase and succinic dehydrogenase positive, both of which were known as a marker of eccrine gland, but acid phosphatase negative, which was a marker of apocrine gland, and these results suggested the tumor differentiated towards eccrine glands.

Additional reports are required in order to better understand the nature of this disease.

References

1. Helwig EB. Eccrine acrospiroma. J Cutan Pathol 1984; 11: 415-20.

2. Kao GF, Helwig EB, Graham JH. Aggressive digital papillary adenoma and adenocarcinoma; A clinicopathological study of 57 patients, with histological, immunopathological, and ultrastructural observations. J Cutan Pathol 1987; 14: 129-46.

3. Duke WH, Sherrod TT, Lupton GP. Aggressive digital papillary adenocarcinoma (aggressive digital papillary adenoma and adenocarcinoma revisited). Am J Surg Pathol 2000; 24: 775-84.

4. Paties C, Taccagni L, Papotti M, et al. Apocrine carcinoma of the skin: A clinicopathologic, immunocytochemical, and ultrastructural study. Cancer 1993; 71: 375-81.

5. Jih DM, Elenitsas R, Vittorio CC, et al. Aggressive digital papillary adenocarcinoma. A case report and review of the literature. Am J Dermatopathol 2001; 23: 154-7.

6. Aki T, Shimao S, Kanbe N, Sasaki N, et al. A case of aggressive digital papillary adenoma. (In Japanese) Tokyo: Rinsho Derma, 1989; 31: 1415-9.

Article accepted on 8/6/02