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Epidermal mucinosis in mycosis fungoides
Dermatopatholog¥ II
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Epidermal mucinosis in mycosis fungoides Brian J. Nickoloff, M.D., Ph.D., Stanford, CA In many cases of mycosis fungoides there is widening of the epidermal intercellular spaces (i.e., spongiosis) and papillary dermal fibrosis with minimal papillary dermal edema. Twenty biopsies of mycosis fungoides, stained with a modified colloidal iron procedure, were analyzed to substantiate the notion that the spongiosis resulted from the formation of an osmotic gradient because of intercellular acidic mucopolysaccharide deposition. In nineteen of twenty cases of patch-plaque mycosis fungoides, there was positive intercellular deposition of acidic mucopolysaccharides. In addition to the contribution of acidic mucopolysaccharides to the process of spongiosis, the biologic significance of epidermal mucin deposition is discussed. Mycosis fungoides should be added to the growing list of diseases in which there is epidermal mucinosis. (J AM ACAD DERMATOL15:83-86, 1986.)
Spongiosis has been variably defined by dermatopathologists, but basically it can be identified when the intercellular space between keratinocytes is widened (as noted in a review by Stenn et all). There are various causes of spongiosis and varying degrees of spongiosis, which in the extreme form produces microvesicle formation. From a pathophysiologic standpoint, the precise mechanism of spongiosis is unclear, z.a One previous hypothesis implicated the pathogenetic formation of an osmotic gradient toward the epidermis.' In this hypothesis, epidermal cells were suggested to produce extracellular ions or proteins that, by the establishment of a Gibbs-Donnan equilibrium, would draw fluid across the basement membiane zone by osmotic forces, z My colleagues and 13have previously speculated that follicular spongiosis resuits from the intercellular deposition of waterbinding acidic mucopolysaccharides that were recognized by positive colloidal iron staining. We suggested that follicular spongiosis and follicular mucinosis differ by virtue of the degree of follicular mucin deposition but that intercellular mucin could be identified in both cases in which there
was increased widening of the spaces between follicular epithelium. In many cases of the patch-plaque stage of mycosis fungoides, widening of the intercellular space where the atypical lymphocytes are infiltrating has been observed, and this report documents the presence of colloidal iron-positive material in these zones. Thus mycosis fungoides should be added to the list of diseases (basal cell carcinoma, verruca vulgaris, keratoacanthoma, squamous cell carcinoma, and spongiotic dermatitis) in which there is epidermal mucinosis. 4 In contrast to this study's cases of mycosis fungoides, in which the epidermal mucinosis is accompanied by a papillary dermis with coarse or thickened collagen, the allergic contact dermatitis and other types of spongiotic dermatitis, in which there may be general epidermal mucinosis, are accompanied by papillary dermal edema. This differential diagnostic point is emphasized because of the possible diagnostic dilemma that arises in distinguishing mycosis fungoides from other dermatitides that have variable degrees of widened intercellular spaces and lymphocytic infiltrates, s
From the Department of Dermatology, Stanford University Medical Center,
MATERIALS AND METHODS
Reprint requests to: Dr. Brian J. Nickoloff, Director of Dermatopathology, R - t 6 6 , Stanford University Medical Center, Stanford, CA 94305.
The last fourteen consecutive patients (1984 to 1985) with the patch or plaque stage of mycosis fungoides whose biopsies were processed in the Stanford Der83
84
Journal of the American Academyof Dermatology
Nickoloff
Fig. 1. Patch stage of mycosis fungoides. Spongiosis and intercellular colloidal ironpositive material are most prominent in the mid and lower epidermis. The lower epidermis is infiltrated by enlarged hyperchromatic lymphocytes. The papillary dermis is fibrotic, with scattered atypical lymphocytes. ( × 250.) Figs. 2 and 3. Higher magnification confirms the widened intercellular spaces containing colloidal iron-positive material. The infiltrating lymphocytes are markedly hyperchromatic, with irregular nuclear contours. (Fig. 2: × 500; Fig. 3: ×700.)
matopathology Laboratory were participants in this study. All specimens were initially fixed in 10% neutral buffered formalin and processed in a Technicon, which included an initial postformalfn fixation for 1 hour in Van de Grift's fixative (diluted 1 : 4 with formaldehyde; Anachemia, Champlain, NY). In addition to routine hematoxylin-and-eosin stains, acidic mucopolysaccharides were identified with the use of the colloidal iron reaction in combination with a periodic acid-Schiff stain plus diastase (modified Mowry's colloidal iron stain utilizing 10% potassium ferrocyanide solution with 20% hydrochloric acid: All patients had discontinued the use of any topical or systemic medication for at least 4 weeks prior to their biopsy. Cases of follicular mucinosis with mycosis fungoides, S6zary syndrome, or lymphomatous panniculitis were not in-
cluded in this series. A total of twenty shave biopsies from fourteen patients comprised this study. The patients included nine women and five men with an age range of 29 to 86 years. Sites of biopsies included the cheek (one case), upper extremity (three cases), trunk (eleven cases), and buttocks (five cases). RESULTS The criteria for the assessment of mycosis fungoides included those previously published by several previous investigators. 79 In all cases diagnosed as mycosis fungoides there was a moderately dense, superficial, bandlike infiltrate composed of atypical-appearing lymphocytes with enlarged hyperchromatic nuclei with irregular nu-
Volume 15 Number 1 July, 1986 clear contours accompanied by variable numbers of plasma cells and eosinophils. The atypical lymphocytes infiltrated the epidermis as single cells, with rare clusters in the epidermis. All twenty biopsies interpreted as representing mycosis fungoides had widening of the intercellular spaces and a spongiotic appearance that was generally more pronounced in the lower and mid epidermis than in the upper, more superficial epidermis. No microvesicles were identified in the epidermis, and there were varying degrees of spongiosis that did not necessarily, correspond to the degree of epidermotropism by atypical-appearing lymphocytes. In nineteen of twenty biopsies, colloidal ironpositive material was clearly identified in the epidermal areas of widened intercellular spaces (Figs. 1 to 3). The appearance of the acidic mucopolysaccharides varied from fine and evenly coated, elongated intercellular bridges to small droplets. No large pools of acidic mucopolysaccharide were identified. The adjacent normal-appearing epidermis had only rare focal areas in which a faint blue reaction product could be identified outlining the keratinocyte cell membrane. The basement membrane zone did not appear thickened, and although there was papillary dermal fibrosis, only scanty acidic mucopolysaccharides were seen in the subbasement membrane zone of the papillary dermis without prominent edema. In the lower papillary dermis and upper reticular dermis, there were patchy focal areas of acidic mucopolysaccharide deposition. The degree of epidermal mucin deposition appeared to parallel the degree of spongiosis, and in the one case in which colloidal iron-reactive material was not seen, there was only slight widening of the intercellular spaces. It should be noted that in cases of mycosis fungoides with widening of the intercellular spaces, in which colloidal iron stains were performed before 1983, less positivity was seen. This variation could have been due to differences in fixation (no exposure to Van de Grift's fixative) or the use of the unmodified colloidal iron staining procedure. DISCUSSION Although it has been appreciated for some time that acidic mucopolysaccharides (hyaluronic acid)
Epidermal mucinosis in mycosis fungoides
85
are present in normal and diseased skin, t° recognition of these acidic mucopolysaccharides as contributing mechanistically to spongiosis has not been previously proposed. In nineteen of twenty biopsies of mycosis fungoides in which there were widened intercellular spaces, intercellular mucin deposition was identified by the colloidal iron reaction. It is doubtful that the widened intercellular spaces result from excessive water or hydrostatic pressure in the papillary dermis that expands through the basement membrane zone, since minimal papillary dermal edema and, often, dense fibrosis are present, but there are no apparent vascular abnormalities in the superficial vascular plexus. ~ Rather, the water is drawn by osmotic forces toward the epidermis, 1 and we believe that keratinocyte-derived acidic mucopolysaccharides are responsible for this osmotic gradient. The histologic findings in these twenty shave biopsies of the patch-plaque stage of mycosis fungoides are in agreement with those previously published, 9 in that there was epidermal spongiosis without microvesiculation, as well as little or no edema of the papillary dermis. By contrast, in spongiotic dermatitis there also may be epidermal mucinosis, with the epidermis containing microvesiculation and prominent papillary dermal edema. In spongiotic dermatitis, hydrostatic pressure forces in the dermis may play a more important pathophysiologic role in the development of spongiosis than in mycosis fungoides. Finally, what is the possible biologic significance of widened intercellular spaces containing acidic mucopolysaccharides? First, the widened intercellular spaces result in less keratinocyte cellto-cell surface contact. In psoriasis this alteration of cell surfaces with decreased "contact inhibition" has been suggested to be responsible for the increased mitotic rate in psoriasis. ~ It is of interest that in this study, colloidal iron-positive material has been observed in the widened intercellular spaces of many psoriatic plaques, and the mycosis fungoides biopsies displayed varying degrees of acanthosis. Second, the mucinous epithelial interstitium has been previously suggested to have important metabolic exchange properties and to mask surface antigens, t2 Alteration in the degree of acidic mucopolysaccharide deposition may pro-
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Journal of the American Academy of Dermatology
Nickoloff
vide p a t h w a y s for migrating inflammatory and malignant cells and m a y facilitate metabolic exchange and/or r e m o v a l o f internal products to the external milieu. 12 T h e i m m u n o l o g i c and biochemical properties o f the epithelial m u c i n o u s interstitium need further clarification. It s h o u l d be r e m e m b e r e d that one hypothesis regarding the cause o f mycosis fungoides is that it results f r o m chronic antigenic stimulation. 13 In this context the i m m u n o m o d u l a t o r y role o f acidic m u c o p o l y s a c c h a r i d e s with respect to either the initiation or maintenance o f an epid e r m a l - l y m p h o c y t e interaction takes on new significance. The i m p o r t a n c e o f glycosaminoglycans and extraeellular matrix interaction in embryology, physiology, and neoplasia has only recently been emphasized. 14.~5With new k n o w l e d g e o f the mechanism o f spongiosis and clarification o f the r o l e o f epidermal acidic m u c o p o l y s a c c h a r i d e s in benign dermatitides and m y c o s i s fungoides, it is to be h o p e d that new insight into the cause and treatment o f these conditions will emerge.
REFERENCES 1. Stenn KS, Balin AK, Higgins T, Stenn JO: Spongiosis. J AM ACAD DERMATOL5:213-214, 1981. 2. Ackerman AB: More about spongiosis. Am J Dermatopathol 6:419-420, 1984. 3. NickoloffBJ, Wood C, Farber EM: Follicular spongiosis with intercellular deposition of mucin: Observations and speculations. Am J Dermatopathol 7:302-303, 1985.
4. Hempstead RW, Ackerman AB: Follicular mucinosis: A reaction pattern in follicular epithelium. Am J Dermatopathol 7:245-257, 1985. 5. Ackerman AB, Breza TS, Capland L: Spongiotic simulants of mycosis fungoides. Arch Dermatol 109:218220, 1974. 6. Luna LG, editor: Manual of histologic staining methods of the Armed Forces Institute of Pathology, ed. 3. Washington, DC, 1968, the Institute, pp. 167-168. 7. Rappaport H, Thomas LB: Mycosis fungoides: The pathology of extracutaneous involvement. Cancer 34:11981229, 1974. 8. Samman PD: Mycosis fungoides and other cutaneous reticuloses. Clin Exp Derrnatol 1:197-214, 1976. 9. Sanchez JL, Ackerman AB: The patch stage of mycosis fungoides. Am J Dermatopathol 1:5-26, 1979. 10. Johnson WC, Helwig EB: Histochemistry of the acidic mucopolysaccharides of skin in normal and in certain pathologic conditions. Am J Clin Pathol 40:123-131, 1963. 11. Orfanos CE, Schaumburg-Lever G, Mahrle G, Lever WF: Alterations of cell surfaces as a pathogenetic factor in psoriasis. Arch Dermatol 107:38-46, 1973. 12. Reed RJ: The T-lymphocyte, the mucinous epithelial interstitium and immunostimulation. Am J Dermatopathol 3:207-314, 1981. 13. Cohen SR, Stenn KS, Braverman IM, Beck GJ" Mycosis fungoides: Clinicopathologic relationships, survival and therapy in 59 patients with observations on occupation as a new prognostic factor. Cancer 46:2654-2659, 1985. 14. Bemfield M, Rapraeger A, Jalkanen M, Banerjee SD: Matrix interactions in epithelial morphogenesis involve a cell surface proteoglycan, in Shibata S, editor: Biology and chemistry of basement membranes. Amsterdam, Elsevier. (In press.) 15. Irelstad RL: Glycosaminoglycans: Mortar, matrix, mentor, Lab Invest 53:1-4, 1985.
ABSTRACTS RU486 inhibits peripheral effects of glucocorticoids in humans Gaillard RC, Poffet D, Riondel AM, et al: J Clin Endocrinol Metab 61:1009-1011, 1985 Steroid blockers are being studied, possibly for use in adrenal disorders. This one blocks the vasoconstrictive effect of steroids in skin. Philip C. Anderson, M.D.
Aging decreases the capacity of human skin to produce D3 MacLaughtin J, Holick MF: J C]in Invest 76:15361538, 1985 D3 is a 7-dehydrocholesterol and 80% of it is produced in the epidermis. Twofold reductions in capacity to pro-
duce D3 may occur with aging but can be corrected easily in the diet. Philip C. Anderson, M.D.
Post-laryngectomy pharyngo-cutaneous fistulae Kent SE, Liu KC, Das Gupta AR: J Laryngol Otol 99:1005-1008, 1985 Dermatologists are experts who must know it all. Fistulas deceive most physicians. About 7% of all laryugectomy patients, as reported in this study, developed a pharyngocutaneous fistula. Watch for these. Philip C. Anderson, M.D.
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Epidermal mucinosis in mycosis fungoides Brian J. Nickoloff, M.D., Ph.D., Stanford, CA In many cases of mycosis fungoides there is widening of the epidermal intercellular spaces (i.e., spongiosis) and papillary dermal fibrosis with minimal papillary dermal edema. Twenty biopsies of mycosis fungoides, stained with a modified colloidal iron procedure, were analyzed to substantiate the notion that the spongiosis resulted from the formation of an osmotic gradient because of intercellular acidic mucopolysaccharide deposition. In nineteen of twenty cases of patch-plaque mycosis fungoides, there was positive intercellular deposition of acidic mucopolysaccharides. In addition to the contribution of acidic mucopolysaccharides to the process of spongiosis, the biologic significance of epidermal mucin deposition is discussed. Mycosis fungoides should be added to the growing list of diseases in which there is epidermal mucinosis. (J AM ACAD DERMATOL15:83-86, 1986.)
Spongiosis has been variably defined by dermatopathologists, but basically it can be identified when the intercellular space between keratinocytes is widened (as noted in a review by Stenn et all). There are various causes of spongiosis and varying degrees of spongiosis, which in the extreme form produces microvesicle formation. From a pathophysiologic standpoint, the precise mechanism of spongiosis is unclear, z.a One previous hypothesis implicated the pathogenetic formation of an osmotic gradient toward the epidermis.' In this hypothesis, epidermal cells were suggested to produce extracellular ions or proteins that, by the establishment of a Gibbs-Donnan equilibrium, would draw fluid across the basement membiane zone by osmotic forces, z My colleagues and 13have previously speculated that follicular spongiosis resuits from the intercellular deposition of waterbinding acidic mucopolysaccharides that were recognized by positive colloidal iron staining. We suggested that follicular spongiosis and follicular mucinosis differ by virtue of the degree of follicular mucin deposition but that intercellular mucin could be identified in both cases in which there
was increased widening of the spaces between follicular epithelium. In many cases of the patch-plaque stage of mycosis fungoides, widening of the intercellular space where the atypical lymphocytes are infiltrating has been observed, and this report documents the presence of colloidal iron-positive material in these zones. Thus mycosis fungoides should be added to the list of diseases (basal cell carcinoma, verruca vulgaris, keratoacanthoma, squamous cell carcinoma, and spongiotic dermatitis) in which there is epidermal mucinosis. 4 In contrast to this study's cases of mycosis fungoides, in which the epidermal mucinosis is accompanied by a papillary dermis with coarse or thickened collagen, the allergic contact dermatitis and other types of spongiotic dermatitis, in which there may be general epidermal mucinosis, are accompanied by papillary dermal edema. This differential diagnostic point is emphasized because of the possible diagnostic dilemma that arises in distinguishing mycosis fungoides from other dermatitides that have variable degrees of widened intercellular spaces and lymphocytic infiltrates, s
From the Department of Dermatology, Stanford University Medical Center,
MATERIALS AND METHODS
Reprint requests to: Dr. Brian J. Nickoloff, Director of Dermatopathology, R - t 6 6 , Stanford University Medical Center, Stanford, CA 94305.
The last fourteen consecutive patients (1984 to 1985) with the patch or plaque stage of mycosis fungoides whose biopsies were processed in the Stanford Der83
84
Journal of the American Academyof Dermatology
Nickoloff
Fig. 1. Patch stage of mycosis fungoides. Spongiosis and intercellular colloidal ironpositive material are most prominent in the mid and lower epidermis. The lower epidermis is infiltrated by enlarged hyperchromatic lymphocytes. The papillary dermis is fibrotic, with scattered atypical lymphocytes. ( × 250.) Figs. 2 and 3. Higher magnification confirms the widened intercellular spaces containing colloidal iron-positive material. The infiltrating lymphocytes are markedly hyperchromatic, with irregular nuclear contours. (Fig. 2: × 500; Fig. 3: ×700.)
matopathology Laboratory were participants in this study. All specimens were initially fixed in 10% neutral buffered formalin and processed in a Technicon, which included an initial postformalfn fixation for 1 hour in Van de Grift's fixative (diluted 1 : 4 with formaldehyde; Anachemia, Champlain, NY). In addition to routine hematoxylin-and-eosin stains, acidic mucopolysaccharides were identified with the use of the colloidal iron reaction in combination with a periodic acid-Schiff stain plus diastase (modified Mowry's colloidal iron stain utilizing 10% potassium ferrocyanide solution with 20% hydrochloric acid: All patients had discontinued the use of any topical or systemic medication for at least 4 weeks prior to their biopsy. Cases of follicular mucinosis with mycosis fungoides, S6zary syndrome, or lymphomatous panniculitis were not in-
cluded in this series. A total of twenty shave biopsies from fourteen patients comprised this study. The patients included nine women and five men with an age range of 29 to 86 years. Sites of biopsies included the cheek (one case), upper extremity (three cases), trunk (eleven cases), and buttocks (five cases). RESULTS The criteria for the assessment of mycosis fungoides included those previously published by several previous investigators. 79 In all cases diagnosed as mycosis fungoides there was a moderately dense, superficial, bandlike infiltrate composed of atypical-appearing lymphocytes with enlarged hyperchromatic nuclei with irregular nu-
Volume 15 Number 1 July, 1986 clear contours accompanied by variable numbers of plasma cells and eosinophils. The atypical lymphocytes infiltrated the epidermis as single cells, with rare clusters in the epidermis. All twenty biopsies interpreted as representing mycosis fungoides had widening of the intercellular spaces and a spongiotic appearance that was generally more pronounced in the lower and mid epidermis than in the upper, more superficial epidermis. No microvesicles were identified in the epidermis, and there were varying degrees of spongiosis that did not necessarily, correspond to the degree of epidermotropism by atypical-appearing lymphocytes. In nineteen of twenty biopsies, colloidal ironpositive material was clearly identified in the epidermal areas of widened intercellular spaces (Figs. 1 to 3). The appearance of the acidic mucopolysaccharides varied from fine and evenly coated, elongated intercellular bridges to small droplets. No large pools of acidic mucopolysaccharide were identified. The adjacent normal-appearing epidermis had only rare focal areas in which a faint blue reaction product could be identified outlining the keratinocyte cell membrane. The basement membrane zone did not appear thickened, and although there was papillary dermal fibrosis, only scanty acidic mucopolysaccharides were seen in the subbasement membrane zone of the papillary dermis without prominent edema. In the lower papillary dermis and upper reticular dermis, there were patchy focal areas of acidic mucopolysaccharide deposition. The degree of epidermal mucin deposition appeared to parallel the degree of spongiosis, and in the one case in which colloidal iron-reactive material was not seen, there was only slight widening of the intercellular spaces. It should be noted that in cases of mycosis fungoides with widening of the intercellular spaces, in which colloidal iron stains were performed before 1983, less positivity was seen. This variation could have been due to differences in fixation (no exposure to Van de Grift's fixative) or the use of the unmodified colloidal iron staining procedure. DISCUSSION Although it has been appreciated for some time that acidic mucopolysaccharides (hyaluronic acid)
Epidermal mucinosis in mycosis fungoides
85
are present in normal and diseased skin, t° recognition of these acidic mucopolysaccharides as contributing mechanistically to spongiosis has not been previously proposed. In nineteen of twenty biopsies of mycosis fungoides in which there were widened intercellular spaces, intercellular mucin deposition was identified by the colloidal iron reaction. It is doubtful that the widened intercellular spaces result from excessive water or hydrostatic pressure in the papillary dermis that expands through the basement membrane zone, since minimal papillary dermal edema and, often, dense fibrosis are present, but there are no apparent vascular abnormalities in the superficial vascular plexus. ~ Rather, the water is drawn by osmotic forces toward the epidermis, 1 and we believe that keratinocyte-derived acidic mucopolysaccharides are responsible for this osmotic gradient. The histologic findings in these twenty shave biopsies of the patch-plaque stage of mycosis fungoides are in agreement with those previously published, 9 in that there was epidermal spongiosis without microvesiculation, as well as little or no edema of the papillary dermis. By contrast, in spongiotic dermatitis there also may be epidermal mucinosis, with the epidermis containing microvesiculation and prominent papillary dermal edema. In spongiotic dermatitis, hydrostatic pressure forces in the dermis may play a more important pathophysiologic role in the development of spongiosis than in mycosis fungoides. Finally, what is the possible biologic significance of widened intercellular spaces containing acidic mucopolysaccharides? First, the widened intercellular spaces result in less keratinocyte cellto-cell surface contact. In psoriasis this alteration of cell surfaces with decreased "contact inhibition" has been suggested to be responsible for the increased mitotic rate in psoriasis. ~ It is of interest that in this study, colloidal iron-positive material has been observed in the widened intercellular spaces of many psoriatic plaques, and the mycosis fungoides biopsies displayed varying degrees of acanthosis. Second, the mucinous epithelial interstitium has been previously suggested to have important metabolic exchange properties and to mask surface antigens, t2 Alteration in the degree of acidic mucopolysaccharide deposition may pro-
86
Journal of the American Academy of Dermatology
Nickoloff
vide p a t h w a y s for migrating inflammatory and malignant cells and m a y facilitate metabolic exchange and/or r e m o v a l o f internal products to the external milieu. 12 T h e i m m u n o l o g i c and biochemical properties o f the epithelial m u c i n o u s interstitium need further clarification. It s h o u l d be r e m e m b e r e d that one hypothesis regarding the cause o f mycosis fungoides is that it results f r o m chronic antigenic stimulation. 13 In this context the i m m u n o m o d u l a t o r y role o f acidic m u c o p o l y s a c c h a r i d e s with respect to either the initiation or maintenance o f an epid e r m a l - l y m p h o c y t e interaction takes on new significance. The i m p o r t a n c e o f glycosaminoglycans and extraeellular matrix interaction in embryology, physiology, and neoplasia has only recently been emphasized. 14.~5With new k n o w l e d g e o f the mechanism o f spongiosis and clarification o f the r o l e o f epidermal acidic m u c o p o l y s a c c h a r i d e s in benign dermatitides and m y c o s i s fungoides, it is to be h o p e d that new insight into the cause and treatment o f these conditions will emerge.
REFERENCES 1. Stenn KS, Balin AK, Higgins T, Stenn JO: Spongiosis. J AM ACAD DERMATOL5:213-214, 1981. 2. Ackerman AB: More about spongiosis. Am J Dermatopathol 6:419-420, 1984. 3. NickoloffBJ, Wood C, Farber EM: Follicular spongiosis with intercellular deposition of mucin: Observations and speculations. Am J Dermatopathol 7:302-303, 1985.
4. Hempstead RW, Ackerman AB: Follicular mucinosis: A reaction pattern in follicular epithelium. Am J Dermatopathol 7:245-257, 1985. 5. Ackerman AB, Breza TS, Capland L: Spongiotic simulants of mycosis fungoides. Arch Dermatol 109:218220, 1974. 6. Luna LG, editor: Manual of histologic staining methods of the Armed Forces Institute of Pathology, ed. 3. Washington, DC, 1968, the Institute, pp. 167-168. 7. Rappaport H, Thomas LB: Mycosis fungoides: The pathology of extracutaneous involvement. Cancer 34:11981229, 1974. 8. Samman PD: Mycosis fungoides and other cutaneous reticuloses. Clin Exp Derrnatol 1:197-214, 1976. 9. Sanchez JL, Ackerman AB: The patch stage of mycosis fungoides. Am J Dermatopathol 1:5-26, 1979. 10. Johnson WC, Helwig EB: Histochemistry of the acidic mucopolysaccharides of skin in normal and in certain pathologic conditions. Am J Clin Pathol 40:123-131, 1963. 11. Orfanos CE, Schaumburg-Lever G, Mahrle G, Lever WF: Alterations of cell surfaces as a pathogenetic factor in psoriasis. Arch Dermatol 107:38-46, 1973. 12. Reed RJ: The T-lymphocyte, the mucinous epithelial interstitium and immunostimulation. Am J Dermatopathol 3:207-314, 1981. 13. Cohen SR, Stenn KS, Braverman IM, Beck GJ" Mycosis fungoides: Clinicopathologic relationships, survival and therapy in 59 patients with observations on occupation as a new prognostic factor. Cancer 46:2654-2659, 1985. 14. Bemfield M, Rapraeger A, Jalkanen M, Banerjee SD: Matrix interactions in epithelial morphogenesis involve a cell surface proteoglycan, in Shibata S, editor: Biology and chemistry of basement membranes. Amsterdam, Elsevier. (In press.) 15. Irelstad RL: Glycosaminoglycans: Mortar, matrix, mentor, Lab Invest 53:1-4, 1985.
ABSTRACTS RU486 inhibits peripheral effects of glucocorticoids in humans Gaillard RC, Poffet D, Riondel AM, et al: J Clin Endocrinol Metab 61:1009-1011, 1985 Steroid blockers are being studied, possibly for use in adrenal disorders. This one blocks the vasoconstrictive effect of steroids in skin. Philip C. Anderson, M.D.
Aging decreases the capacity of human skin to produce D3 MacLaughtin J, Holick MF: J C]in Invest 76:15361538, 1985 D3 is a 7-dehydrocholesterol and 80% of it is produced in the epidermis. Twofold reductions in capacity to pro-
duce D3 may occur with aging but can be corrected easily in the diet. Philip C. Anderson, M.D.
Post-laryngectomy pharyngo-cutaneous fistulae Kent SE, Liu KC, Das Gupta AR: J Laryngol Otol 99:1005-1008, 1985 Dermatologists are experts who must know it all. Fistulas deceive most physicians. About 7% of all laryugectomy patients, as reported in this study, developed a pharyngocutaneous fistula. Watch for these. Philip C. Anderson, M.D.