Brilish Ituinial of Dermatology (1992) 126, 257-261.

Eccrine syringotibroadenoma: a case report with analysis of cytokeratin expression F.ECKERT. M.NILLES* AND M.ALTMANNSBERGERt I'k'partmnit of Dcrmuiolntifi. ilniwrsHu of Muithli. Gcnmiiin Departments of*Dermat('loiiii ami "ffiKfio/m/y, University ofUicsseii, Germany Accepted for publication 16 October 1991

Summary

A 56-year-old tnan presented with a 30-year history of a slowly enlarging lesion on the sole of his right foot, A biopsy showed an anastomosing network of stnal! cuboidal cells with the fortnation of occasional sweut ductal lumina and u marked librovascular stroma. The histological findings were interpreted as consistent with the diagnosis o! an eccrine syringofibroadenoma. Using innnunohistochemistry all the tumour cells were positively stained by the pan-cytokeratin antibody Lu-5 and an antibody to the cytokeratins 1/S/lO/l 1, In addition the luminal ductal cells expressed cytokeratin 1 9 and CEA. Tumour cells were negative forcytokeratins I, 7. 8, 13 atid 18 and did not express vimentin and GCDFP-1 5. The results indicate that the eccrine syringofibroadenoma is differentiated towards the dermal eccrine duct.

In 1963, Mascaro described two neoplasms consisting of anastomosing cords and strands of epithelial cells surrounded by a richly iibrovascnlar stroma. Within some ofthe epithelial strands tubular structures like those of sweat gland ducts were noted. Emphasizing a close bistologicai similarity between these neoplasms and other fibroepithelial tumours, such as fibroepithelial tumour of Pinkus. he introduced the term 'eccrine syringoiibroadenoma',' Until now, only a few cases of this rare neoplasm have been described in detail.^ "'^ We present the histological and immunohistochemical features of a case of eccrine syringofibroadenoma with special reference to the expression ofthe cytokeratins.

Metlwds Tissue for light microscopy and immunohistochemica! studies was fixed in 4% neutral-buffered ibrmalin. processed overnight using graded ethanols and xylene and subsequently embedded in paraffin wax. Paraffin sections were stained with haematoxylin and eosin and PAS. lmmunostaining with monoclonal antibodies was performed using the alkaline phosphatase-anti-alkalinephosphntase (AP A API-technique,'" Control sections consisted of known positive specimens. For negative controls, the primary antibodies were replaced by nonimmune ascites Huid, The monoclonal antibodies, specificities, sources of reagents and results of immunohistochemistry are detailed in Table 1.

Methods Case report

A 56-year-old man presented with a nodular lesion on the sole of his right foot which had slowly enlarged over the past 30 years. On examination there was a 1-2 x l-O cm partially eroded lesion and a clinical diagnosis of Bowen's disease was made. Eollowing a biopsy which revealed a benign adnexal tumour, the lesion was surgically excised and 2 years later, there had been no recurrence.

Correspondence: Dr l'.Eckert, [department of Dermatology, University of Regensburg, I'.O, Box l()nf)62. 0 8 4 0 0 , Regensburg, Germany.

Results The lesion showed thin anastomosing strands of cuboidal tumour cells extending from the epidermis to the upper dertnis (Fig. 1), The cells were pale and sharply demarcated frotn the epidermis {Fig. 2), Small ductal structures were occasionally visible within the interconnected strands of cells (Fig. 3). The stromal component of the tumour showed marked fibrosis associated with prominent dilated blood vessels and a perivascular lymphohistiocytic infiltrate (Fig. 2), At the base of the lesion normal eccrine sweat glands could be seen and 257

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F.ECKERT et al.

Antibody

Specilk'ity

34^4 J4/ffil2 IJ)S-68

CKl*

Enzot

CKl/5/l()/n

Enzo Sigma;}:

4.1.IS CY-9() hi 70

CK8 CKI8 CKI9

Ksl i.l l.u-5 V9 BRST-2 Atiti-CEAtt

CK13 CKl-19 Vimentin GCDFP-IS CEA

CK7

Results

Source

BMij Sigma Gift of M.Osbom Progenl BM BM Signet**

Dakota

lablf I. Iiiimunobistocbemistry of eccrine sy ri ngodbroadcnom a

Negative All tumour cells positive Weak positivity contiiicd to cuticula of luminal cells Negative Negative Positivity confined to luminal ductal tumour cells Negative All tumour cells positive Negative Negative Positivity confined to the luminal side of ductal tumour cells

t t Polyclonal antibody. ' CK. cytokeralin. numbered acrording tn the catalog of Moll et «/. t Hnzo BiochemiciiIs, New York, NY. U.S.A. I Sigma. Dciscnhofcn. Gcnnimy. i) lioehritigcr Mannheim, Mannheim, Germany. 1 Progcn. Heidelberg. Germany. " Signet. Uedham. U.S.A. $:j: Dako, Hamburg, Germany.

Figure 1. Anastomosing strands of cuboidal tumour cells extending from the epidermis to the upper dermis. Deep in the lesion, eccrine ductal and secretory structures can be seen (hacmatuxylin and eosin. x2-5).

figure 2. Detail of i^'igurc L The tuninur cells arf sharply Llemarcated from the adjacent epidermis. The siromal component shows increased vascularity and fibrosis (haematoxylin and eosin. x 20).

ECCRINE SYRINGOFIBROADENOMA



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259

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tk

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V

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Figure 3. Detail of Figure I. Ductal differentiation within a strand of tumour cells (haeraatoxylin and eositi. x 40|.

Figure 4. The tumour cells are uniformly labelled by the antibody to CK 1/5/10/11 (APAAP. x20).

these were not connected with the tumour as revealed by examining serial sections.

lesion occurs mostly in older patients as a solitary nodule, papule or tumour. Multiple lesions may sometimes be seen in a linear arrangement. The association of eccrine syringofibroadenoma with other tumours such as papillary syringoadenoma.'- clear cell acanthoma.'' verrucous eccrine poroma.'^ and with hidrotic ectodermal dysplasia'"* '"• has been described. Differential diagnoses include eccrine poroma and Hhroepithelial tumour of Pinkus. In contrast to eccrine poroma, eccrine syringofibroadenoma is characterized by a network of thin, anastomosing epithelial cords. The structure may resemble that of the libroepithelial tumour of Pinkus, but ductal lumina are absent in this tumour. While the histological characteristics have been detailed in most of the studies, little is known about the immunohistochemical features of syringofibroadenoma and these are limited to two studies.'' • Mehregan (•( al. analysed two cases of this tumour with an anti-eccrine gland monoclonal antibody (KKH6} using an indirect immunoperoxidase technique.'' Both of the tumours

Immunoh istochem istry All the tumour cells were labelled by the monoclonal antibody to cytokeratin polypeptides 1/S/lO/l 1 (Fig. 4) and by the pan-cytokeratin antibody Lu-S. Expression of CK19 was restricted to the luminal ductal cells (Fig. 5). Weak CK7 staining was observed at the luminal border of the ductai cells, whereas the cytoplasm remained unstained. Anti-CEA antibody reacted with the luminal side of the ductal tumour cells. All the tumour cells were negative for CKl. CK8. CK13. CK18, vimentin aud tiCDFP-15.

Discussion Recently. Hurt et al. reviewed the clinical and histopathological spectrum of eccrine syringofibroadenoma.'^ This

2M)

F.ECKERT el ul.

o

I'igurt" 5. CK 1 9 is expressed in luminal ductal cells, whereas the other cells remain unstiiined (APAAP. x 20).

were positive within the strands of the tumour epithelium. As previously shown EKH6 reacts with the eccrine secretory cells and also partially with cells of the eccrine coiled duct."' Thus, while suggesting the eccrine nature of syringofibroadenoma this antibody did not yield more precise information as to the differentiation of the tumour cells. Further immunohistochemical studies were performed by Kanitakis et alJ who analysed one case of eccrine syringotjbroadenoma using antibodies to keratin (KLl land involucrin. There was strong staining of KL] in all the tumour cells, while positivity for involucrin was confined to the ductal structures of the tumour. Based on these findings an acrosyringeal differentiation of the tumour was assumed.' With the advent of monoclonal antibodies specific to keratin subsets and individual keratin polypeptides. it has become feasible to analyse epithelial tumours on a molecular basis. We applied a panel of monoclonal antibodies to keratin subsets and individual keratin

polypeptides to elucidate the differentiation pathway in eccrine syringofibroadenoma. All tumour cells were positively stained by an antibody to cytokeratin polypeptides 1/5/10/11. while expression of CKiy was only seen in luminal ductal cells of the tumour. All tumour cells were negative for CKl and CKs 7. 8. and IK. typical of simple epithelia. Furthermore, anti-CKA marked the luminal surface of the ductal cells. GCDFP-1 5 was not expressed, which is in line with the probable ecrrine differentiation of this tumour.'' In normal eccrine sweat glands CK 1 is consistently found in the intermediate eells of the distal portion of the dermal duct and in the outer cells of the acrosyringium."^ ''^ In contrast. CKl is not expressed in luminal and outer (basal) cells of the dermal duct.'^ All portions of the duct are labelled by the antibody to CK 1/5/10/11. while CKiy is restricted to the luminal ductal cells.''' These cells are also characterized by the expression of CEA along the luminal surface.''* "' The CKs 7 and 18 are only expressed in the acini of the eccrine sweat gland.'" With regard to the cytokeratin pattern of normal eccrine sweat glands, the majority of tumour cells in our case resembled outer (basal) cells of the dermal duct, whereas few cells showed difierentiation towards luminal ductal cells. Thus, the cytokeratin pattern of the tumour largely corresponded to tlie CK pattern of the dermal eccrine duct and not to the CK pattern of the acrosyringium. The negative reaction for CKl in eccrine syringofibroadenoma does not necessarily indicate the absence of this cytokeratin polypeptide. Small amounts of cytokeratin polypeptides may escape immunohistochemical detection, especially in formalin-fixed tissue. However, eccrine syringofibroadenomas may display heterogeneity of cytokeratin expression reffecting differences in the state of differentiation. Heterogeneity of CKl expression has been found in eccrine poroma. a tumour that is closely related to the eccrine syringofibroadenoma.''' In conclusion, while others''" have suggested that syringofibroadenoma represented a neoplasm of eccrine acrosyringeal cells our findings do not support this concept, especially with regard to the cytokeratin pattern of this tumour. In our view the histological and immunohistochemical findings show a close interrelationship between the cell difTerentiation of the ecerine dermal duct and eccrine syringofibroadenoma. On current evidence we believe the term eccrine syringofibroadenoma reflects most appropriately the cellular differentiation of the tumour.

ECCRiNE SYRINGOFIBROADENOMA

Acknowledgments We thank E.Ebmeyer and E.-M.Eusebio for expert technical assistance. We are grateful to M.Osborn, Gottingen, tiermany for providing the monoclonal antibody bl 70.

References

2 J 4 5

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o jM, Considerations sur les tumeurs Hbro-epitheiiales: Le syringofibroadcnome eccrine. Ann Dermatol Suphiligr 1963; 90: 14f.-5.i. Ogino A. Linear eccrine poroma,(4r(:/ii>mtfltr>/ \97(y. 112: 841-4. Wet'don 0. Ix-wis J. Acrosyringeal nevus. / (.'uian Pathi'l I 977: 4: \(ih-ti. Olmos [., Syringofibroadenoma ecrino dc Mascaru. Actas Ik-nnosifiliofir I9«(>: 71: 7i-fi. Civiitte ), le;ininougin M, Barrandon Y. limenen de Fninch I, Syringofibroadenonui ecrinn dc Mtisiraro. i)isciisi()n de un oaso. Med Cntiin tbcro Lit Am 1981; 9: 193-6. Mehregaii AH. Maruli M. Medenlcu M. Efcriiie syringoKbroadenoma (Mascaro). Report of two cases. / Am Acad Dennato) 1985; H:4i5-6. Kanitakis 1. Zambruno C f^luvrard S ct al. licfrine syringofibroadenonia. ImiiiunohistolngiCHl study of a new case. Am J DennatoIHKhot 1987:9: i7-4().

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1 S Aloi FCi. Torre C. Hidrotic ectoderniat dysplasia with diffuse eccrine syringofibroadenomatosis. Arch Dermatol 1989: 125: 1715. If) Hashimolo K, l-,to H, Matsumoto M. Hori K. Anti-keratin monoL-lonal aniibodk's: production, specilicities and applications. / CiiUiii Pathol 1983; 10: 529-39. 1 7 MiiKOtijiiin G. MargolLs R. Immunohistochemistry of gross cystic disease fluid protein KICDFI'-l 51 in (i5 benign sweat gland tumors of the skin. Am / Dcrmalopallwl 1988; 10: 28-35. 18 Broekaerl D, Cornille A. Bto H el nl. A comparative immitnohistochemicai study of cytokeralin and vimentin expression in middle ear mucosa and cholesteatoma. and in epidermis. Virchows Arch [A] 1988:413: 39-51. 19 Eckert F. Nilles M. Betkc M et al. Das ckkrine Forom—liine klinischpathologisehe und immunhistnlogische Studic unter besonderer Beruck.sit.-iitit;Ling der Tumomelldiflerenzierung. Hmitarzt (I" press). 21) Maiorana A. Nigrisoli E, Papolli M. Immunohlstochemical markers of sweat gland Uimors./C'iJtiifiPiKfiiiJ 1986: 13: 1S7-96. 2 ! Cotton DVVK. Inimunoliistochemical staining of normal sweat glands. Br ] Dn-mi>tol i9Sfi: 1 1 4 : 4 4 1 - 9 .

Eccrine syringofibroadenoma: a case report with analysis of cytokeratin expression.

A 56-year-old man presented with a 30-year history of a slowly enlarging lesion on the sole of his right foot. A biopsy showed an anastomosing network...
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