Carcinosarcoma arising in eccrine spiradenoma. A clinicopathologic and immunohistochemical study of two cases.

Malignant change in a benign eccrine spiradenoma is rare. Only 13 such cases have been previously reported. Two further cases are described herein, both of which were carcinosarcomas and arose in middle-aged women. In each case continuity was demonstrated between the benign and malignant epithelial components and the sarcomatous element. In case 1 the sarcomatous component showed osteocartilaginous and rhabdomyoblastic differentiation, whereas in case 2 only osteosarcoma was evident. To our knowledge, carcinosarcoma has not been previously described arising in eccrine spiradenoma. The literature regarding malignant eccrine spiradenoma is reviewed.

A case report of equivocal neoplasm originating from an apocrine gland on the eyelid.

We report a rare case of apocrine neoplasm with malignant potential. The patient, a 29-year-old man, had a nodule 1 cm in diameter on his left upper eyelid which had been growing slowly for several years. It was a cystic lesion, consisting of neoplastic cells of probable apocrine gland or Moll's gland origin. This opinion was based on the histological characteristics, which included eosinophilic cytoplasm accompanied with decapitation secretion, iron granules, and granular depositions which were stained positively with periodic acid-Schiff, with and without diastase digestion. Ferritin was found in their cytoplasm, a feature that has not been reported. It was uncertain whether the neoplasm was benign or malignant, because the cells showed nuclear atypia, characterized by variation in size and hyperchromasia, but lacked the histological features of malignancy, including infiltration into the adjacent tissue and mitosis.

Identification of parathyroid hormone-related protein in canine apocrine adenocarcinoma of the anal sac.

The presence of parathyroid hormone-related protein (PTHrP) in the apocrine adenocarcinoma tumor line (CAC-8) derived from a hypercalcemic dog was demonstrated by western and northern blot analyses. Western blots of CAC-8 tumor extracts revealed a major protein with a molecular weight of approximately 18,000 daltons that cross-reacted with antiserum to human PTHrP. Northern blots demonstrated multiple-sized messenger RNA transcripts in CAC-8 that hybridized to a full-length cDNA probe to human PTHrP. Adenocarcinomas derived from apocrine glands of the anal sac also were stained immunohistochemically for antigens that cross-react with antiserum to human PTHrP. The tumor line (CAC-8) maintained in nude mice stained positively for PTHrP in 13 of 24 tumors. Three of ten apocrine adenocarcinomas from dogs with hypercalcemia stained for PTHrP, whereas zero of ten tumors were positive from normocalcemic dogs. Normal canine epidermal keratinocytes and areas of squamous metaplasia in a perianal gland carcinoma also were positive for PTHrP. These data demonstrated that canine tissues contained a homologue to human PTHrP that likely is important in the pathogenesis of humoral hypercalcemia of malignancy.

Immunohistochemical demonstration of ferritin in sweat gland and sweat gland neoplasms.

Using a rabbit anti-human liver ferritin antibody, we examined the binding patterns of this reagent in normal skin and observed a unique binding pattern limited to the outermost layer of the eccrine duct. Examination of a variety of sweat gland neoplasms revealed 2 distinct patterns. One was the binding of this antibody to the outermost layer of cells in the epithelial cords of syringoma, producing a characteristic ring when seen in cross-section. This pattern of binding did not occur in other neoplasms known to be related to the eccrine duct such as dermal duct tumor and eccrine poroma. Only sparse sporadic binding occurred in other eccrine and apocrine neoplasms. A second characteristic binding pattern, not related to that noted in syringoma and diffuse in pattern, was seen in acrospiroma and in a number of adnexal carcinomas. Diffuse ferritin expression has been described in malignant neoplasms in tissues other than skin. Diffuse ferritin staining of certain sweat gland neoplasms may be an indication of biologic activity and potential aggressivity of these neoplasms.

Multiple apocrine hidrocystomas on the eyelids.

A 31-year-old man with multiple cystic tumors symmetrically distributed on his eyelids is presented. Histopathology and immunohistochemistry suggest the diagnosis of apocrine hidrocystomas. Apocrine hidrocystomas occur frequently on the face, but multiple and symmetrical occurrence on the eyelids has not been reported up to now.

Mixed tumors of the skin. A histological and immunohistochemical study.

Sixty-four specimens of mixed tumors of the skin were studied by conventional microscopy. Sections from all 64 specimens were stained by hematoxylin and eosin, and sections from 18 of those specimens were stained by immunoperoxidase techniques for the presence of S-100 protein, carcino-embryonic antigen (CEA), keratin, actin, vimentin, epithelial membrane antigen (EMA), and gross cystic disease fluid protein-15 (GCDFP-15). Two distinctive histopathological patterns of mixed tumors of the skin became apparent, namely, apocrine and eccrine. Mixed tumors with apocrine features are by far the most common. Immunoperoxidase techniques, in our experience, do not enable differentiation between apocrine and eccrine types of mixed tumors.

Clear cell hidradenoma with whorl formation of squamoid cells: immunohistochemical and electron microscopic studies.

Many groups of squamoid cells arranged in whorls were found in a case of clear cell hidradenoma. These cells showed positive staining for carcinoembryonic antigen, but S-100 protein was not detected. Electron microscopic examination showed considerable amounts of tonofilaments, but neither keratohyalin granules nor multivesicular dense bodies were present in these cells. These features suggest that the constituting cells of whorls differentiated toward the eccrine ductal cells, in particular the intraepidermal ductal cells.

[An immunohistochemical study of cutaneous tumors using an antibody to the breast cyst fluid protein (GCDFP-15)].

The antibody against a molecular weight 15,000 protein isolated from the breast cyst fluid (GCDFP-15) was applied to tissue from cutaneous tumors, especially to sweat gland tumors. This protein was purified from the breast cyst fluid; antisera was prepared in rabbits. Ninety six cases of cutaneous tumors were stained by the PAP method. Apocrine hydrocystoma, syringocystadenoma papilliferum, so-called mixed tumor of the skin, extramammary Paget's disease, microcystic adnexal carcinoma, and mucinous carcinoma of the skin were positively stained. Eccrine poroma, eccrine spiradenoma, syringoma, eccrine hydrocystoma, papillary eccrine adenoma, adenoid type of basalioma were negative. These observations indicate that the positively stained tumors have functioning seromucous cells, which are characteristic of apocrine gland cells and eccrine dark cells in the skin.

A monoclonal antibody, SKH1, reacts with 40 Kd sweat gland-associated antigen.

Several monoclonal antibodies (MAB) have been produced using an eccrine carcinoma cell line as an immunogen. One such MAB, SKH1, reacted with both the secretory portion and coiled duct of the eccrine and with the secretory portion of apocrine gland. SKH1, however, did not react with myoepithelial cells, intradermal ducts of both types of sweat gland, or with other components of normal axillary skin including the epidermis and follicular apparatus. The reaction was strongest if the specimen was fixed with 80% methanol, and moderate on non-fixed or acid-alcohol-fixed specimens. Only weak reaction was obtained on cold acetone-fixed specimens, and reaction was negative with formalin-fixed, paraffin-embedded tissues. SKH1 reacted positively with the cytoskeleton of the eccrine carcinoma cell line, Colo-16 and MCF-7. Applied to pathological skin specimens, SKH1 reacted with the tumor cells of clear cell hidradenoma, syringocystadenoma papilliferum, and extramammary Paget's disease. SKH1 also reacted with the tumor cells of metastatic adenocarcinomas arising from lung, breast and ovary. SKH1 did not react with the majority of tumor cells of eccrine poroma, but reacted with single-layered cells lining narrow ductal lumina. SKH1 did not react with epithelial cells lining cystic or ductal lumina of syringoma, but reacted moderately with the amorphous keratin-like substance filling the lumina. Immunoblot analysis revealed that SKH1 recognizes a 40 Kd sweat gland-associated antigen, and can be an aid to identifying tumors arising from sweat gland structures.

Gross cystic disease fluid protein-15 as a marker for breast cancer: immunohistochemical analysis of 690 human neoplasms and comparison with alpha-lactalbumin.

The identification of metastatic carcinoma of the breast may be difficult in the absence of a previous history of breast cancer. Various immunophenotypic markers have been introduced to aid in this process. A monoclonal antibody directed at a 15-kilodalton (kd) gross cystic disease fluid protein (GCDFP-15) was applied immunohistochemically to paraffin sections of 105 breast cancers and 585 nonmammary malignancies in order to assess its value in this context. In addition, GCDFP-15 was compared with another putative mammary epithelial marker, alpha-lactalbumin (ALA), with respect to sensitivity and specificity for a diagnosis of breast carcinoma. Overall, the rates of specificity and sensitivity and the predictive value of a positive result for GCDFP-15 were 95%, 74%, and 74%, respectively. Corresponding statistical parameters for ALA were 50%, 50%, and 23%. A consistent congruency between the reactivity patterns of primary and metastatic breast cancers was noted for GCDFP-15 but not for ALA. Besides mammary carcinomas, the major tumor types that expressed GCDFP-15 were carcinomas of the salivary glands, sweat glands, and prostate. Since the latter three types of lesions are unlikely to be diagnosed as metastatic breast cancer, statistical indices were recalculated after exclusion of these three tumor types. Following this exclusion, the adjusted rate of specificity of GCDFP-15 and the predictive value of a positive result for a diagnosis of metastatic carcinoma of the breast were each 99%. In contrast, predictive parameters for ALA were not altered. These results show that GCDFP-15 is a specific marker for breast cancer and is superior to ALA in this respect.

A monoclonal antibody which identifies an epitope in eccrine duct and acrosyringium.

A mouse monoclonal antibody obtained after immunization of BALB/c mice with large molecular weight salivary mucins decorated an epitope in eccrine duct and acrosyringium in sections from formalin-fixed, paraffin-embedded tissues. Eccrine coil, apocrine gland and other cutaneous structures were not decorated by the monoclonal antibody. This antibody was used to study the histogenesis of a number of adnexal neoplasms.

Clear-cell syringoma. Immunohistochemistry and electron microscopy study.

Clear-cell syringoma is a histologic variant of syringoma that is otherwise clinically indistinguishable from ordinary syringoma. This variant is formed by cells that have pale or clear cytoplasm as a result of glycogen accumulation. There is a high association of clear-cell syringoma and diabetes mellitus. A case of clear-cell syringoma associated with diabetes mellitus is described. Electron microscopic examination revealed that periluminal cells showed intra- and extracytoplasmic multivesicular bodies that may be characteristic of the clear-cell variant. Immunohistochemistry for carcinoembryonic antigen (CEA) showed ordinary syringomas as in the presence of CEA within and surrounding duct-like spaces.

Isolation of 16,000-dalton parathyroid hormone-like proteins from two animal tumors causing humoral hypercalcemia of malignancy.

A 16K PTH-like protein with a unique primary structure has recently been isolated from several human tumors associated with the syndrome of humoral hypercalcemia of malignancy. Certain spontaneous and transplantable animal tumors also cause this syndrome. The responsible mediator in these animal tumors is not known. We report the isolation of 16K proteins from the rat H500 Leydig cell tumor and the canine apocrine cell adenocarcinoma of the anal sac. Both proteins are potent activators of PTH receptor-coupled adenylate cyclase in bone cells. Both proteins demonstrate similarities in amino acid composition to one another and to the human PTH-like protein. Limited amino-terminal sequence information from the canine protein demonstrates homology with the human PTH-like protein. Antibodies raised to a synthetic human PTH-(1-36)-like peptide cross-react with both the rat and canine proteins in an immunoradiometric assay. These data demonstrate that by physical and immunological criteria PTH-like peptides are present in these animal tumors that appear to be closely related to the human PTH-like peptide. These data further suggest that this protein is not unique to humans, but has an evolutionary origin which extends back at least 65-80 million yr.

Human papillomavirus DNA in adenosquamous carcinoma and squamous cell carcinoma of the vulva.

The tissues from 16 cases of adenosquamous carcinoma (pseudoglandular squamous cell carcinoma or adenoacanthoma of the sweat glands of Lever) and 26 cases of invasive squamous cell carcinoma of the vulva were studied for the presence of human papillomavirus (HPV) genomes using Southern blot hybridization on fresh tissues. Types 1, 2, 3, 4, 5, 6, 16, and 18 HPV DNA probes and in situ hybridization were used on formalin-fixed paraffin sections using type 2, 6, 16, and 18 HPV DNA probes. Only one case of adenosquamous carcinoma contained an undetermined type of HPV DNA, whereas five cases of squamous cell carcinoma contained HPV DNA. Three of these five cases contained type 16, one type 6 HPV, and two an undetermined type. These results demonstrate HPV DNA associations with malignancy of the vulva that are similar to those observed elsewhere in the genital tract.

[Apocrine carcinoma of the breast--a morphologic comparison of the apocrine sweat glands and the apocrine metaplastic epithelia in mastopathy].

An operatively removed apocrine carcinoma of the breast from a 62-year-old Japanese lady has been observed by the ABC method, using the monoclonal antibody 115D8. The cancer cells and metaplastic epithelia exhibited similar ultrastructural findings (an apical snout, apocrine granules, etc.) as the apocrine sweat gland cells, although no evidence of apocrine secretion could be detected. The immunohistochemical testing, using monoclonal antibody, 115D8, showed an apical, linear, dot-like, staining in the supranuclear regions on the apocrine sweat gland cells and on the apocrine metaplastic cells of the mammary gland. Similar stainability also was observed in the well-differentiated area of the apocrine carcinoma, while a heterogeneity in staining, such as unstained cells and diffuse cytoplasmic-stained cells were found in the poorly-differentiated areas. These abnormal staining patterns indicate the malignant changes of the apocrine cells.

Immunolocalization of keratin proteins in sweat gland tumours by the use of monoclonal antibody.

A total of 34 cases (eccrine poroma: 2, cylindroma: 2, eccrine spiradenoma: 4, syringocystadenoma papilliferum: 1, hydroadenoma papilliferum: 1, clear cell hydroadenoma: 7, mixed tumour: 16) of sweat gland tumours of the skin were described in terms of immunohistochemical distribution of keratins using polyclonal anti-keratin antiserum (TK, detecting 41-56 KDa keratins) and monoclonal antibodies (KL1, 55-57 KDa; PKK1, 40, 45, 52.5 KDa). Keratin expression in eccrine poroma, spiradenoma and syringocystadenoma was similar to that in the ductal segment of normal sweat glands. Cylindroma showed usually slight staining for kertins. Tumour cells of hydroadenomas showed not so prominent staining for any of the keratins; however, histologically, tumour cells indicated marked variation, and the degree of keratin proteins also was different among these histological variants. Mixed tumours of the skin were strongly decorated with anti-keratin antibodies along the luminal surface cells of typical structures, while no staining occurred in outer side cells. Luminal tumour cells may be differentiated from secretory coil cells, whereas outer side cells may have a myoepithelial origin, as outer layer cells found in pleomorphic adenoma of salivary glands.

Immunohistochemical staining patterns of sweat glands and their neoplasms using two monoclonal antibodies to keratins.

The staining patterns of normal sweat glands and sweat gland-derived neoplasms using 2 monoclonal antibodies to keratins (Dako-CK1, Cam 5.2) has been assessed. Based on findings in normal glands, the differentiation of these benign neoplasms is considered, with positive evidence for apocrine and eccrine differentiation, and in the latter, differentiation to ductal or secretory type epithelia. This easily applied technique (indirect immunoperoxidase) is suitable for use in routinely processed tissue and employs 2 commercially available monoclonal antibodies. The findings may be of assistance in general surgical reporting of problematic cases.

Immunohistochemistry of gross cystic disease fluid protein (GCDFP-15) in 65 benign sweat gland tumors of the skin.

Sixty-five cases of benign sweat gland tumors of the skin were studied for the expression and localization of gross cystic disease fluid protein-15 (GCDFP-15) by immunoperoxidase methods. There was positive staining of tumors of probable apocrine differentiation in 10 of 11 cases of apocrine hidrocystoma and five of five cases of hidradenoma papilliferum. There was no immunoreactivity for GCDFP-15 for tumors of probable eccrine differentiation, including five cases of eccrine hidrocystoma, five cases of eccrine poroma, five cases of eccrine spiradenoma, 10 cases of clear cell hidradenoma, and nine cases of syringoma. There was variable positive staining of tumors of more uncertain histogenesis, including eight of eight cases of syringocystadenoma papilliferum, one of four cases of cylindroma, and two of two cases of chondroid syringoma (mixed tumor). The above data support a functional differentiation of the expression of GCDFP-15 by eccrine compared to apocrine glandular epithelium with benign tumor development.