Porocarcinoma Associated with Extramammary Paget\'s Disease

Journat of Cutaneous Pathology 1974: 1: 249-255

Porocarcinoma Associated with Extramammary Paget's Disease ANA M , ENG' AND CESAR REYES=

'Department of Pathology and Dermatology, Loyola University Medical Center, Maywood, Illinois and Hines Veterans Administration Hospital, Hines, Illinois; and ^Department of Pathology, Hines Veterans Administration Hospital, Hines, Illinois, U,S,A, The coexistence of two tumors, porocarcinoma and extramammary Paget's disease (FMP) in one tissue section, facilitates a subtle but distinct differentiation of the two cell types. The adjacent occurrence of the two tumors perhaps indicates a common origin in their benign form. The biologic mechanism of the Pagetoid phenomenon is demonstrated, (Received for pttbticatiott December 20, 1974)

Although there have been numerous reports on EMP disease, some of which were related to sweat gland carcinoma, only a few were shown to be associated with an intraepidermal tumor. Our case exemplifies the stjbtle differentiation of potocarcinoma and Paget's cells because of their adjacent locat i o n in a single tissue specimen. This not only supports inditectly their relationship b u t also probably sheds sotne light on the derivation of the Paget's cells. Case Report

Clinieal Case I n 1953, a 77-year-old white man had a nodular scrotal growth surrounded by an ulcerated weepy dermatitis. Seventeen years later an excisional biopsy of the 4 X 3 J/2 c m growth was done. The histopathologic sections are shown in Figs, 1, 2, 3 and 4, In August 1972, a left orchiectomy, left groin dissection and split thickness graft were performed. The sections of the tumor

tissue showed an epidermal papillary tumor with dermal invasion (Figs. 5, 6, 7 and 8). In March 1973, metastases led to the death of the patient, Histopathologie Observatiotts Fig, 1 shows an epidermal growth with acanthosis and papillomatosis, papillary villous formation and cystic invaginations (Fig, 1, Area B), Figs, 2, 3 and 4 are magnified views of areas A & B, respectively, of Fig, 1, The cells in areas A & B appear different despite their location adjacent to each other. The cells in Figs. 2 and 3 are two to three times the size of adjacent epidermal cells and are arranged singly along the basal cell layer or in acini-like groups (Fig, 3, arrow). The nuclei are pale and vesicular and the cytoplasm is pale and eosinopbilie with fibrillar changes. The mucicarmine stain is strongly positive. The cells in Fig. 4 are slightly smaller but with a larger nucleus to cytoplasmic ratio, more pleomorphic than those in Fig. 3. There is no acinus

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Fig. I. Transition of extramammary Paget's disease (A), followed by the primary sweat gland tumor (B). H & E, X 16.

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formation in the serial sections made from the tissue block. The rnucicarmine stain is only weakly positive in area B. The cells of the papillary portion of the tumor (Fig. 1, Area B) retained their identity even though specimens were obtained at different times and from different sites (Figs. 5, 6, 7 and 8). The cell types of Figs. 5, 6, 7 and 8 appeared similar to those in Fig. 1, Area B. Figs. 7 and 8 demonstrate the manner of tumor colonization of the epidermis. Fig. 6, a magnified view of the papillary tumor in Fig. 5, shows a layer of small cuboidal basophilic cells delimiting tbe tumor cells from the Fig. 2. Higher magnification of Area A of Fig. I. Extramammary Paget's cells started singly along the basal cell layer and gradually form into groups. H & E , X ]30.

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Fig. 3. Higher magnification of Eig. 2 showing large Paget's cells, compressed cells, foci of luminal formation (arrows), and progression of growth into the higher epidermal layer H & E , X 250.

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Fig. 4. Higher magnification of Area B of Fig. 1. The carcinoma cells are large, with prominent nuclei and abundant cytoplasm. H & E , X 400.

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vascular and cellular dermis. Eig. 7 shows the gradual spread of tumor cells along the rim of the nortnal epidertnal cells (arrow). The tumor cells here are slightly larger, more basophilic and show a tnore vacuolated cytoplasm than the normal epidermal eells. Fig. 8 further distinguishes the normal epidermal cells from its tumor cells. Cleftlike spaces within the tumor cells located between the basement membrane and prickle eell layer are visible. On autopsy tbere was a superficial 1 % cm ulcerating cancer of the penis and also multiple metastatic loci in the paraaortic, mediastinal, hilar and supraclavieular lytnph

„, Fig. 5. Papillary villous-like sweat gland tumor. H & E, X 13.

nodes, as well as in the lungs, pleura, diaphragtn and spleen. The colon, rectum, anus and urinary bladder were without tumor. Microscopically, the metastatic tumor appeared as sheets, lobules and nests of malignant cells. The cells were large and polygonal with abundant pink vaeuolated cytoplasm and dark, slightly pleomorphic nuclei. Some of the cells showed pseudoacinar formations. Extensive areas of mitosis and necrosis wete common in the metastatic tumors. There was no evidence of squatnous differentiation. The nuteicarmine stain was negative in the cells examined.

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Fig. 6. Higher magnification of Fig. 5. The eaneerous cells have the same morphology as the initial biopsy specimen shown in Fig. 4. H & E. X 250.

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/ i ' . 7. Paget phenomenon; the gradual spread of cancerous cells are seen along the rim of t h e normal epidermis (arrows). H & E , X 100.

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Fig. 8. Paget phenomenon; sweat gland tumor cells and normal keratinocytes are well distinguishable. H & E , X 250.

Discussion

The lesion started as a nodular and weepy dermatitis which recurred despite surgery and eventually metastasized, Histopathologically, a papillary intraepidertnal tumor and a less acanthotic Paget's tumor corresponds to the nodular and weepy clinical lesion respectively. Fig, 1 (A & B) demonstrates Ihe adjaeent location of two distinct growths which were seen in magnified views in Figs, 2, 3, 4, 6 and 8, Figs, 1 (B), 4, 6 and 8 all showed similar cell types arranged in a papillary pattern in varying degrees. Other intraepidermal tumors such as squamous cell carcinoma and trialignant tnelanoma do not assume villouslike papillary formation and are, therefore, not likely diagnoses. This intiaepidetmal tumor bore features striking identical to porocarcinoma (Mishima & Morioka 1960),

It is conceivable Ibat porocarcinoma represents the malignant phase of eccrine poroma. The cells seen in Figs. 4, 6 and 8 were large, pleomorphic in size and staining, witb formed clefts, rich in glycogen and poor in mucin. It is of interest that the papillary pattern simulates another tumor, syringocystadenoma papilliferum. That porocarcinoma and syringocystadenoma papilliferum might be related is likely, since eccrine poroma (the benign form of porocarcinoma) and syringocystadenoma papilliferum share similar ultrastructural and enzymatic reactions, has led some investigators (Hashimoto & Lever 1968) to believe that both are eccrine derived. In eontrast to the porocarcinoma cells, the adjacently located Paget's cells (Figs, 2 and 3) were richer in mucin, show a smaller nuclear-cytoplasmic ratio and less pleotnotphism, with formed alveolar luminal spaces. Serial sections of the block failed to show

POROCARCINOMA ASSOCIATFD WITH EMP

transition cell types between the porocarcinoma cells and the Paget's cells; however, one cannot rule out entirely the possibilty tbat the two distinct cell types tnight still represent one single entity since we do not have a three dimensional dissection of the entire block. On the other hand, association of EMP's tumor with another adjacent tumor has been reported. A case of squamous cell carcinoma iti situ and Paget's disease occurring adjacently but discreetly in the same section was described by Montgomery (1967). Also reported was a patient with E M P disease (supported by histochemical stains) with malignant melanoma occurring in the same groin area (Becker et al. 1960), A case of Paget's disease of the perianal skin with associated but morphologically separated adenocarcinoma was reported by Yoell & Price (1960). If such occurrences were real, then the concept that the frequent association of EMP with other tumors is caused by a .single carcinogenic stimulus is tenable, Pagetoid phenomenon i.s the colonization of foreign cells in the epidermis by carcinoma cells from various other organs and even from ihc epidermis itself. The way in which this Pageloid phenomenon occurs is similar to the spread of atypical epidermal cells along Ihc outer surfaces of hair follicles and leprcssion of the adnexal cells as seen in Bowen's disease and actinic keratosis (Pinkus & Mehregan 1969). In our case, however, the converse is true; the porocarcinoma cells crept along tbe outer surface of the epidermal cells (Fig. 7) and

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spread laterally lo occupy the epidermis above the basement membrane (Fig. 8). Awareness of the subtle but clear distinction of porocarcinoma and Paget's cells and an understanding of the biologic mechanism of the Pagetoid phenomenon, aids in the interpretation of investigative studies of EMP disease. References Becker, S. W., Brennan, H. & Weichselbaum, P. K. (1960) Genital Paget's disease. Archives of Dermatology 82, 857-864. Hashimoto, K. & Lever, W. F. (1968) Appendage Tumors of the Skin, pp. 46-47, Springfield: Charles C. Thomas. Mishima, Y. & Morioka, S. (I960) Oncogenic differentiation of the intraepidermal eeerine sweat duct: eccrine poroma, poroepithelioma and porocarcinoma. Dermatologica 138, 239-250. Montgomery, H. (1967) Deriiuitoixjthology, pp. 1009. New York: Harper Row. Pinkus, H. & Gould, S. E. (1939) Extramammary Paget's disease and intraepithelial carcinoma. Archives of Dertiuitology 39, 479502. Pinkus, H. & Mehi-egun, A. H. (1969) A Guide to Derintitohistopathology, pp. 410. New York: Applelon-Century-Crofts. Yoell, J. H. & Price, W. G. (1960) Paget's disease of the perineal skin with associated adenocarcinoma. Archives of Dermatology 82, 986-991.

Address: Ana M. Eng Dept. of Pathology Hines Veleratis Adnii/iistration Hospital Hines Illinois 60141, U.S.A.