Paget Cells Research Articles

Electron microscopy in in situ and invasive vulvar Paget's disease

Electron microscopic studies of two cases of vulvar Paget's disease (1 invasive and 1 in situ) were undertaken in an attempt to elucidate further the histogenesis of the characteristic Paget cell. Secretory vesicles, mitochondria, ferritin-like granules, and membrane junctional structures are described which are typical of apocrine cells. These findings, plus the location of some cells against the basement membrane, support the hypothesis that the Paget cell is an apocrine cell differentiating within a more generalized epithelial neoplasm.

Ultrastructure of perianal Paget's disease.

The fine structural characteristics of a case of perianal Paget's disease are presented. These include the presence of secretory and nonsecretory Paget's cells forming lumens and intercellular canaliculi, pleomorphic mitochondria, fine cytoplasmic filaments, convoluted plasma membranes containing microvilli, and poorly developed desmosomes. These findings are interpreted as favoring an eccrine sweat gland origin in the extramammary and lactiferous ductal origin in the mammary form of the disease. Insofar as the histogenetic origin of Paget's cells is concerned, the assumption of epidermotropic migration from an underlying carcinoma is favored over the concept of malignant conversion of the intra-epidermal sudoriferous or squamous epithelium.

Ultrastructural Study of a Case of Extramammary Paget's Disease of the Vulva

Extramammary Paget's disease of the vulva was found in a 75-year-old woman. The ultrastructural features of Paget cells include rare desmosomes between two Paget cells as well as between Paget cells and adjacent keratinocytes, occasionally giant mitochondria, abundance of cytoplasmic organelles, microvilli, and thick bundles of filaments not connected with plasma membrane. The keratinocytes frequently showed decreased numbers of desmosomes, moderate numbers of plasma membrane extensions resembling microvilli, rarefaction, and dispersion of tonofilament bundles, and an increase in cytoplasmic vesicles and ribosomes. The keratinocyte alterations and Paget cells ultrastructure suggest that Paget cells may originate from keratinocytes.

Electron microscopical investigation of the morphology of paget cells

Bei einem extramammaren Morbus Paget wurden die elektronenmikroskopische Struktur von Paget-Zellen (Pz) in der Epidermis, besonders im Vergleich mit veranderten Keratinocyten (Kc) untersucht. Es last sich folgendes finden: 1. Die vorwiegend in der unteren Epidermis gewucherten Pz weisen submikroskopisch keine einheitliche Gestalt und einheitliche innere Struktur auf. 2. Die Anzahl, Lange, Dicke, Elektronendichte und Laufart der in Pz erkennbaren feinen Filamente, die gelegentlich angedeutete „Kreuzungsmuster“ ohne echte Tonofibrillenbildung zeigen, sind von Zelle zu Zelle, stellen weise sogar in der gleichen Zelle, verschieden. 3. Zwischen Pz erkennbare, weitgehend kleiner strukturierte Desmosomen weisen gelegentlich, abgesehen von einer schwacheren Elektronendichte, fast normalen Aufbau wie Kc auf. 4. Deutliche Einlagerung von Glykogen, vermehrte Ribosomen, gut entwickeltes endoplasmatisches Reticulum und Golgi-Apparate, mehrere lysosomartige Organellen und langere Mikrotubuli in Pz sind fur die Identifizierung der Zellen nur quantitativ bemerkenswerte Befunde. 5. Melanosomen in Pz sind gewohnlich als grosere „Melanosomenkomplexe“, gelegentlich aber auch einzeln zu erkennen. 6. Der groste Teil der Zellen mit Zellteilungsfiguren in der veranderten Epidermis enthalt mehr oder weniger sichere Tonofibrillen, wahrend diejenigen ohne Tonofibrillen nur selten sind. 7. Intracellulare Tonofilament-Desmosomen-Komplexe (T-D-Komplexe) finden sich haufig in den den Pz benachbarten Kc, sogar bei Zellteilung. Diese T-D-Komplexe lassen sich auch in dyskeratotischen Tonofibrillenmassen in Kc bemerken und ahnlich auch in Pz. 8. Einige Epidermiszellen zeigen, abgesehen von einer kleineren, aber dickeren Tonofibrillenmasse zuweilen Zellstrukturen, die solchen in Pz identisch sind. Eine genaue morphologische Identifizierung dieser Zelle scheint unmoglich zu sein.

Triple Extramammary Paget's Disease

Bilateral axillary and genital Paget's disease occurred in a 77-year-old man. All three lesions were histologically confirmed. Both axillary lesions were surgically excised and the genital lesion was subjected to topical chemotherapy with 5% fluorouracil cream under occlusion. The therapy was only partially successful because the reepithelializing follicular or apocrine duct epithelium contained the Paget's cells. The remaining lesion was treated with radiation. Simultaneous occurrence of Paget's disease in more than two separate regions appears quite exceptional.

Fine structure of the extramammary Paget's cell.

The ultrastructural features of extramammary Paget's cells were examined with a view to elucidating their nature and origin. Extramammary Paget's cells are clearly involved in producing a secretory product which is “packaged” via the Golgi apparatus. Their subcellular organelles were compared with those found in cells of the skin appendages that are involved in active secretion. The two types of cells found in eccrine sweat glands, light and dark, did not basically resemble the extramammary Paget's cell. The light cells produce an aqueous secretion which is not packaged, whereas the membrane-bound product of the dark cells is contained within large vacuoles and is generally very electron dense. The sebaceous gland cells differed quite strikingly also. The basic aspects of the apocrine gland cell compare most favorably with the extramammary Paget's cell, even though some differences still exist. The key comparison lay in the striking similarity of the secretory mechanisms of the two cell types. Both produced the secretory product as a small vacuole, with generally clear contents. The accompanying features of such activity, namely an extensive Golgi apparatus and endoplasmic reticulum, also compared closely. The unusual catabolic vacuoles seen in the apical cap of apocrine cells were not evident in the extramammary Paget's cells, although modest numbers of autophagic vacuoles were present. In spite of the differences that can be noted between these Paget's cells and apocrine cells, it is felt that they are minor, and that the greatest similarity exists between these two.

Further Observations on Paget's Cell

Electron microscopic features of both mammary and extramammary Paget's cells were described as well as findings of cultured extramammary Paget's cell. From the findings, it was concluded that: There were no differences between findings of mammary and extramammary Paget's cells. There were a few or no kertionsome in the kerationocyte of the lesions. Poor differentiation of tonofilament, desmosome and keratohyalin were also encountered in Paget's cells. The Paget's cell is one of dedifferentiated cells rather than degenerated one. The origin of Paget's cell could not be determined only by its morphological findings.

Paget's disease of the breast

More than a hundred years ago Velpeau first described the nipple lesion we now know as Paget’s disease of the breast. However, it was James Paget who in 1874 observed the association between the nipple erosion and breast cancer. Since then, in almost a century, the pathologic aspects of the disease have been the subject of considerable discussion. There is general agreement today that the Paget cell, first described by Darier in 1889, and seen in the nipple epidermis, is a carcinoma cell invading the epidermis of the nipple and originating from an intraductal carcinoma of the underlying duct system of the nipple or breast. Uncertainty still exists, however, about the clinical behavior of this type of carcinoma and its treatment. Poor over-all survival, even with radical mastectomy, has been reported by Colcock and Sommers [I], Helman and Kliman [2], Maier et al [3], and Kay [4]. These generally unfavorable results are particularly disturbing in view of the fact that Paget’s disease is one of the most slowly evolving forms of cancer. Possible explanations of this paradox may be found in the smallness of the reported series of cases and lack of precise information as to the classification and stage of advancement of the disease. The purpose of this report is to elucidate the behavior of Paget’s disease in correlation with its clinical classification, stage, and pathologic extent in a large series of patients treated uniformly and followed up for a long period of time.

Further investigation of extramammary Paget's disease with special reference to electron microscopically discernible granular substances in Paget cells

Further investigation of extramammary Paget's disease with special reference to electron microscopically discernible granular substances in Paget cells

Histochemical study of the alcianophilia of Paget cells in extramammary Paget's disease.

By applying the concept of critical salt concentration to the differentiation of polyanions, the alcianophilia of the cytoplasm of Paget cells was compar-ed with that of melanoma cell cytoplasm. Methylation, saponification, and hyaluronidase, sialidase, ribonuclease and desoxyribonuclease digestions were employed in a further attempt to identify histochemically various polyanions. The results suggest that the alcianophilia of the cytoplasm of Paget cells is mainly due to carboxyl group-containing polyanions, while that of melanoma cell cyto-plasm is related to nucleic acid.

A histochemical study of lactic dehydrogenase in Paget cells.

By the use of a modified incubating medium, lactic dehydrogenase in Paget cells was histochemically examined. The addition of phenazine methosulfate to the substrate solution decreased the reaction intensity of lactic dehydrogenase in Paget cells. In the presence of potassium cyanide, however, phenazine methosulfate caused increased reaction. When urea was introduced into the substrate solution, the lactic dehydrogenase reaction of malpighian cells was strikingly decreased, while the reaction of Paget cells was not decreased so much. The reaction in the sections, which were incubated in the excess lactate-containing solution, was slightly decreased in these two cells. On the basis of biological and biochemical considerations, these facts appear to indicate that there was a metabolic difference between normal malpighian cells and Paget cells.

Observations on intradermal migration of paget cells

1.1. A case of Paget's disease of the vulva is presented documented by histochemical studies.2.2. An observation lending credence to the theory of intradermal migration as the mode of spread of Paget's disease is reported here.3.3. Principles regarding surgical management of this entity are discussed in this report.

Histochemical Study of Mucin Occurring in the PAGET Cell of Extramammary PAGET's Disease

An investigation into the histochemistry of a mucin occurring in the PAGET cell was made of extramammary PAGET's disease of 3 cases.1. The mucin was identified by its positive periodic acid-SCHIFF, periodic acidphenylhydrazine-SCHIFF, alcian blue and toluidine blue staining abilities. The periodic acid-SCHIFF reaction was decreased by methylation as well as sialidase digestion and by mild acid hydrolysis, and the periodic acid-phenylhydrazine-SCHIFF reaction was completely blocked by these treatments. The alcianophilia and toluidine blue metachromasia were blocked by methylation and largely decreased by mild acid hydrolysis and sialidase digestion.2. The mercuric bromphenol blue reaction was moderately found in the cytoplasm of the PAGET cell.3. From the evidence presented, it is concluded that the mucin occurring in the PAGET cell is a sialic acid-containing mucopolysaccharide-protein complex.

HISTOCHEMICAL DEMONSTRATION OF TRANSGLYCOSYLASES AND OXIDATIVE ENZYMES IN THE PAGET CELLS OF EXTRAMAMMARY PAGET'S DISEASE.

1. An enzymohistochemical study of the PAGET cells in extramammary PAGET's disease has been presented. The enzymes examined included uridinediphosphate glucose-glycogen transferase, phosphorylase, and the enzymes of the EMBDENMEYERHOF pathway, the pentose shunt, the TCA cycle and the cytochrome system.2. Each enzyme of the EMBDEN-MEYERHOF pathway, the pentose shunt, the TCA cycle, and the cytochrome systemm was increased or unchanged in the PAGET cells, in comparison with that in the malpighian cells. In contrast, no phosphorylase activity was found in the PAGET cells, although uridinediphosphate glucose-glycogen transferase reaction and glycogen were demonstrated.

EPIDERMOTROPIC ECCRINE CARCINOMA. A CASE COMBINING FEATURES OF ECCRINE POROMA AND PAGET'S DERMATOSIS.

Ordinarily it is not profitable to use single atypical cases for deductions of general nature. However, once in a while, a freak case illuminates a confused and debated field just because it presents singular and ruledefying features. A case of this kind, in the experience of one of us (H.P.), was the man who had a mucin-producing adenocarcinoma of the rectum in the usual location, 8 cm from the anus, which had metastasized widely in the body. It also was associated with clinically typical Paget's disease of the perianal skin, much in the fashion in which the skin around a carcinomatous milk duct becomes affected in the mammary form of Paget's dermatosis. Mucin-bearing cells, resembling Paget cells, were present in the anal and perianal epidermis 1 and were thought to have originated in the rectal carcinoma as suggested earlier by Muir 2 and others. The case lent support to the

Extramammary Paget's disease. A report of two cases.

The initial case report in the United States of extramammary Paget's disease, by Hartzell, foretold the confusion and controversy which was to follow. Hartzell's 1 case was not one of the disease, and a number of similar papers subsequently appeared in the literature. Weiner, 2 Pinkus, 3 and others have contributed much to clarify the subject both clinically and pathologically. The purpose of this paper is to present the clinical appearance, the pathology and therapy, of one mild and one fatal case of extramammary Paget's disease. The autopsy findings which revealed widespread metastases in the latter case will be presented, and the histogenesis of the Paget cell will be discussed. Report of Cases Case 1.— A white male, age 75, was seen on Aug. 18, 1959, complaining of an eruption of one year's duration in the groin. On examination there was an erythematous exudative plaque measuring 2×3 cm. located in the

Extramammary Paget's disease

A case of extramammary Paget's disease of the perianal skin with widespread metastases in a fifty-nine year old white man is presented. This represents approximately the twentyninth recorded example of this disease, and only the second in which widespread metastatic disease has been unequivocally demonstrated. Analysis of previous examples of extramammary Paget's disease reveals it to represent a primary carcinoma of the sweat glands associated with epidermal changes with cutaneous manifestations similar to those of Paget's disease of the breast. The occurrence of the epidermal involvement represents the only morphologic and clinical feature differentiating this disease from other examples of metastasizing carcinoma of the sweat glands. Morphologic evidence is presented which indicates that the primary tumor in this case was derived from apocrine glands, and that the so-called “Paget cells” represent its epidermal metastases.

Paget's disease of the nipple.

Summary(1) macroscopically, paget's disease of the nipple may present a variable picture. in the majority of cases the lesion is red, raw and granular in appearance, but in others, it may be eczematous or dry andscaling. paget's disease should be suspected when any nipple lesion persists for more thanthree to four weeks.(4) microscopically characteristic changes are seen. typical paget cells occur around the edge of the lesion, whilst centrally the superficial layers of the epidermis may be lost.(5) carcinoma is present in the underlying breast in 75 per cent. of cases when first seen.(6) in those cases without a palpable tumour, treatment should be as for carcinoma of the breast.

PAGET'S DISEASE OF THE VULVA

THE CLINICAL picture that Paget¹described in 1874 as a disease of the mammary areola preceding cancer of the mammary gland was soon known to have not only characteristic clinical features but also a peculiar microscopic picture, which entitled it to be classified in a separate group of cutaneous epitheliomatoses. When it was observed that similar pathologic changes could be diagnosed in regions of the skin other than the mammary areola, there began a prolonged controversy as to the precise nature and site of origin of Paget's disease and its peculiar cells (to which the term Paget's cells has been applied), which still persists. The disease is rare. The nipple is the commonest site; women are more commonly affected than men. However, among the 33 published cases of extramammary Paget's disease, 14 have been described as affecting the external genital organs; only 8 cases have been accepted, as far

Paget's disease of the nipple

1. 1. Paget's disease is a malignant disease from its onset even when there is only an isolated involvement of the nipple, the disease having the potentialities of any other malignant tumor. It starts at the junction of the lactiferous duct with the epidermis and spreads toward the skin and into the duct system. A deep seated scirrhous carcinoma is part and parcel of the same disease. 2. 2. A specimen for biopsy should be obtained in all doubtful cases. The characteristic intra-epithelial Paget cells in the epidermis and in the ducts and the characteristic subepithelial inflammatory reaction are diagnostic. 3. 3. Local treatment to the nipple is useless. Radical mastectomy offers the best opportunity for cure.