Necrobiosis Lipoidica: A Histopathological and Histochemical Study*

Vol. 44, No. 6

THE JOURNAL OF INVESTIGATIVE DERMATOLOGY

Printed in U.S.A.

Copyright C 1965 by The Williams & Wilkins Co.

NECROBIOSIS LIPOIDICA: A HISTOPATHOLOGICAL AND HISTOCHEMICAL STUDY* HOWARD R. GRAY, M.D., JAMES H. GRAHAM, M.D. AND WAINE C. JOHNSON, M.D.

Urbach (1), in 1932, described necrobiosis lipoidica diabeticorum as a complication of diabetes nwllitus. Oppenheim (2) later in 1932, reported another patient with diabetes

lipoidica diabeticorum and 17 biopsy specimens from 14 patients with necrobiosis lipoidica were

who had the same cutaneous involvement and used the term dermatitis atrophicans lipoides diabetica. Since then necrobiosis lipoidica diabeticorum has been generally the term used for this skin disease associated with diabetes. Many examples of necrobiosis lipoidica ot associated with diabetes have been reported (3—5) and the incidence of associated diabetes is variously reported from 25 to 87% (6—10). Necrobiosis lipoidica diabeticorum occasionally precedes clinical evidence of diabetes (6, 9). The establishment of definite histopathologic criteria for the differentiation of necrobiosis lipoidica in the diabetic or potential diabetic patient from necrobiosis lipoidica in the non-diabetic patient would be a valuable adjunct in the early diag-

studied. Also, biopsy material from 25 consecutive patients with granuloma annulare was studied. Clinical data was obtained from clinical records, questionaires, personal interviews, and examina-

tion of the patient. All specimens were fixed in 10% neutral buffered formalin and most of the tissue was processed for routine paraffin-blocked sections. Multiple sections stained with hematoxylin and eosin were examined from all patients.

Sections of representative specimens from 5 patients each with necrobiosis lipoidica diaheticorum, necrobiosis lipoidica and granuloma annulare were

prepared by the following methods: periodic acid-Schiff (PAS) reaction, with and without diastase digestion; colloidal iron reaction (12), with and without bovine testicular hyaluronidase digestion for 1 hour at 37° C.; Snook's reticulum stain; Movat's pentachrome I stain (13); Gomori's

aldehyde-fuchsin technic; and the alcian blue method. The pH of the working solutions, and the methods used in the aldehyde-fuchsin and

alcian blue techniques and detailed interpretation of the results were similar to those described by and Helwig (14) and Johnson, Graham Rollins and Winkelman (11) in '1960 re- Johnson and Helwig (15). Frozen, sections were prepared ported identical clinical appearance but differ- from the forinalin-fixed tissue from 1 patient with ent histopathologic patterns in necrobiosis necrobiosis lipoidica diabeticorurn, 3 patients with necrobiosis lipoidica and 1 patient with granulorna lipoidica in diabetic and non-diabetic patients. annulare, and these were stained with the oil red nosis and management of these patients.

The present paper is a report of histopatho- O stain for fat. With the exceptions given, the procedures were carried out as outlined in the material of necrobiosis lipoidica from patients "Manual of Histologic and Special Staining Technics" (16). with and without diabetes. Clinical Data MATERIALS AND METHODS The clinical appearance of the lesions in diaFor purposes of this report the term necrobio- betic and nondiabetic patients was similar and logical and histochemical observations of biopsy

clinical differentiation could not be made (Fig. 1

sis lipoidica diabeticorum is used to designate the cutaneous disease occurring in patients with diabetes, and necrobiosis lipoidica refers to the eruption in patients without diabetes. Twenty-one biopsy specimens from 13 patients with necrobiosis

and 2). The lesions appeared as brownish-red patches with a central yellowish hue and varied in size and shape. The involved skin appeared shiny, waxy, and atrophic and the superficial blood

vessels were usually telangiectatic. Most of the This investigation was supported in part by re- lesions were slightly scaly and a few showed search training grant no. 2A-5289 (C2), from the ulceration and scarring. About half of the patients National Institute of Arthritis and Metabolic had symmetrical involvement of the anterior asDiseases, U. S. Public Health Service, Bethesda, pect of the legs. A few patients had involvement

of only one leg, ankle or dorsal surface of the Presented by title at the Twenty-fifth Annual foot. One patient with diabetes had a solitary leMeeting of The Society for Investigative Derma- sion of the lateral aspect of the right upper arm and tology, Inc., San Francisco, Calif., June 21—23, 1964. another had multiple lesions of the anterior aspects Received for publication June 29, 1964. * From the Skin and Cancer Hospital of Phila- of the legs, left thigh and left hip. Necrobiosis Lipoidica Diabeticorun. The 13 delphia, Department of Dermatology, Temple University School of Medicine, Philadelphia, Pa. patients were all Caucasian. Twelve patients were Maryland 20014.

female and one was male. The age of the pa-

19107.

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Fic. 1. Necrobiosis lipoidica diabeticorum in a 20 year old woman with diabetes for 6

years and skin lesions for 18 months. FIG. 2. Necrobiosis lipoidica in a 49 year old woman with skin lesions for 12 years

tients at the time of the first biopsy examination ranged from 18 to 75 years; the mean age was 44.7 years. The duration of necrobiosis lipoidica diabeticorum from onset to the time of the first biopsy examination varied from 1 month to 5 years; the mean duration was 21 months. Six patients were known to have diabetes prior to the development of the ecrobiosis lipoidica diabeticomm. The duration of diabetes before development of the skin lesions in 4 patients was known and ranged from 1 to 14 years; the mean duration was 6.1 years. Six patients developed cutaneous lesions prior to the onset of clinical symptoms of diabetes mellitus, but laboratory evidence of diabetes was present at the time the diagnosis of necrohiosis lipoidica diabeticorum was established.

The duration of the skin lesion prior to the initial diagnosis of diabetes ranged from 3 months to 11 years; the mean duration was 2.8 years. The pa-

tients were Caucasian and 1 was a Negro. Thir-

teen patients were female and 1 was male.

The age of the patients at the time of the first

biopsy examination ranged from 23 to 60 years. The mean age was 43.5 years. The duration of

necrobiosis lipoidica prior to the first biopsy

examination varied from 9 months to 15 years; the mean duration was 7.9 years. All 14 patients had negative laboratory tests for diabetes and

most patients had been tested at periodic intervals.

The majority of patients had glucose tolerance tests; a few had 2 hour post-prandial blood sugar determinations; one patient not available for further investigation had only a urinalysis. Family history from 11 patients was negative except for 1 patient whose maternal grandmother and maternal aunt had diabetes. Granuloma Annulare. Twenty-two patients were

Caucasian and 3 were Negro. Fifteen patients tient with skin lesions for 11 years had several were female and 10 were male. The age of the biopsy examinations performed before a histo- 25 patients at the time of biopsy examination pathologic diagnosis of necrobiosis lipoidica dia- varied from 2 to 69 years. The mean age was beticorum was made. Nine years after onset a 27.9 years. The disease had been present from borderline fasting blood sugar was reported, but 1 week to 20 years prior to biopsy examination; not investigated. Two years later the patient was the mean duration was 2.4 years. Clinically, all studied and found to have a diabetic type of the patients had lesions characteristic of granu— glucose tolerance curve. Laboratory evidence of loma annulare. The anatomical sites of the biopsy diabetes had probably been present several years. specimens in 23 patients were the lower extremiOne patient noted the onset of cutaneous lesions ties in 9; upper extremities in 10; buttocks in 2; at the time diabetes was initially detected, but the and the posterior aspect of the neck ad external diagnosis of necrobiosis lipoidica diabeticorum ear in 1 each. was ot established until 4 years later. Family HISTOPATHOLOGIC OBSERVATIONS history revealed that 3 of 10 patients had close Hematoxylin- and eosin-stained sections of relatives with diabetes. Necrobiosis Lipoidica. Thirteen of the 14 pa- necrobiosis lipoidica generally showed similar

NECEOBIOSIS LIPOIDICA

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histopathologic changes in the diabetic and the number of small blood vessels in the midnon-diabetic patients, but certain differences corium and deep corium was observed in 9 were observed. In lesions from both diabetic (47%) of the lesions. Groups of 3 to 6 capiland non-diabetic patients the most prominent laries were often observed associated with changes were in the coriurn with areas of nec- fibrosis and a perivascular infiltrate or inflamrobiosis, and a cellular infiltrate composed of matory cells (Fig. 5). The superficial corium, mid-corium and deep variable numbers of lymphocytes, plasma cells,

histiocytes, epithelioid cells and giant cells. corium were all involved in 9 (69%) of the Capillary-endothelial proliferation with thick- 13 specimens in which the entire thickness of ening of the vessel walls and narrowing of the the coriuni was present for evaluation. Six lumina was frequently observed in the mid biopsy specimens were removed too superficially and it was not possible to evaluate all levels corium and deep corium.

Necrobiosis Lipoidica Diabeticorun't. Hema- of the corium. The necrobiotic areas were limited toxylin- and eosin-stained sections from 19 of to the superficial coriuni and mid corium in 2 the 21 specimens from the 13 patients with dia- (15%); deep corium in 1 (8%); and to the betes showed histopathologic changes character-

mid-corium and deep corium in 1 (8%).

istic of active lesions (Fig. 3). The other 2 biNecrobiosis Lipoidica. Hernatoxylin- and opsy specimens were from healed lesions, 1 of eosin-stained section of the 17 biopsy specimens which occurred spontaneously and the other from 14 patients without diabetes showed a occurred after intralesional corticosteroid in- characteristic pattern of histopathologic feajections. Both healed lesions showed only fibro- tures. Epidermal changes were often striking. sis of the corium. The epidermis was essentially Atrophy of the epidermis and associated flatnormal in most of the specimens. Parakerotosis tening of the rete ridges was noted in 7 was present in 3 (16%) of the 19 specimens and (41%) of the specimens (Fig. 6). Slight hypera slight acanthosis in 1 (5%). Necrobiotic areas keratosis was present in only 1 (6%) of the were present in all 19 specimens but the degree specimens. Acanthosis and parakeratosis were of necrobiosis varied. The necrobiotic changes not observed. All 17 specimens showed areas of were minimal in 2 (11%) of the specimens. necrobiosis. The degree of necrobiotic change Fragmented nuclei were usually present in the varied but usually was well developed. Fragareas of necrobiosis. A basophilic staining sub- mented nuclei were usually present in the nec— stance was present in the necrobiotic areas in robiotic areas. A basophilic staining substance 11 (58%). A inflammatory infiltrate was often was present in the areas of necrobiosis in only located about areas of necrobiosis and sections 3 (18%) of the 17 specimens. A prominent from 7 (37%) of the specimens showed a prom- palisaded arrangement of the inflammatory inent palisaded arrangement of the cells. Lym- infiltrate about the necrobiotic areas was noted

phocytes were usually abundant in all the sec- in 4 (24%) of the specimens. Lymphocytes tions. A prominent plasma cell infiltrate was were present in all sections, and the subcutanepresent in 5 (26%) of the specimens. Epithelioid ous fat was usually involved with the inflam-. cells were noted in 12 (63%) and tubercle matory infiltrate. A prominent plasma cell information in 8 (42%). Multinucleated giant filtrate was noted in 9 (53%) of the specimens cells were present in 13 (68%) of the specimens, (Fig. 7). Epithelioid cells and well-developed but only 3 of the 13 showed more than a rare tubercles were present in 12 (71%) of the or occasional giant cell. The giant cells were specimens. Giant cells were noted in 15 (88%) of the foreign body, Langhans, and occasion- of the specimens and large numbers were often ally Touton type. Perivascular inflammation present (Fig. 8). Foreign body, Langhans and was usually present and frequently the walls of occasionally Touton type giant cells were obthe blood vessels were involved. In the sec- served. Capillary-endothelial proliferation and tions with subcutaneous fat present, infiltration thickening of the vessel walls with narrowing with inflammatory cells was observed. Narrow- of the lumina was occasionally noted (Fig. 7). ing of capillary lumina with endothelial prolif- A perivascular inflammatory infiltrate was eration and thickening of the vessel walls often present and this frequently involved the frequently occurred in the mid-corium and walls of the blood vessels. A pronounced indeep corium (Fig. 4). A pronounced increase in crease in the number of capillaries in the mid-

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FIG. 3. Necrobiosis lipoidica diabeticorum showing areas of necrobiosis, palisading of inflammatory cells about the necrobiotic areas and capillary-endothelial proliferation. H & E,

x

50.

FIG. 4. Necrobiosis lipoidica diabeticorum showing capillary-endothelial proliferation, thickening of the vessel walls and narrowing of the lumina. H & E, x 620.

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5. Necrobiosis lipoidica diabeticorum showing groups of capillaries (arrows) near

area of necrobiosis. H & E, X 97. FIG. 6. Necrobiosis lipoidica showing atrophy of the epidermis and flattening of the rete ridges. Elastic fibers stain dark and are absent in the areas of necrobiosis. Aldehyde-fuchsin stain pH 1.7, X 60.

373

374

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a ''r nat waaaaa

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Fi. 7. Necrobiosis lipoidica with a plasma cell infiltrate about a capillary showing endo-

thelial proliferation and thickening of the vessel wall. H & E, X 410. Fx. 8. Necrobiosis lipoidica showing multinucleated giant cells, lymphocytes and plasma cells. H & E, X 410.

NECROBIOSIS LIPOIDICA

375

corium and deep corium was noted in only 2 HISTOCHEMICAL STUDIES (12%) of the specimens. The groups of 3 to 6 Necrobiosis lipoidica diabeticorum, necrobicapillaries in the sections of these 2 specimens were surrounded by an infiltrate of inflamma- osis lipoidica and granulonta annulare showed tory cells.

similar histochemical properties but some varia-

tion in degree of change was observed. The The superficial corium, mid-corium, and necrobiotic areas did not show a significant deep corium were involved in 13 (87%) of the 15 specimens in which the full thickness of amount of glycogen but contained some the coriunt was present in the sections. The PAS-positive diastase-resistant material. This superficial corium and mid-corium were in- latter substance cannot definitely be identified volved in 1 (7%) of these 15 specimens and but may represent a mucopolysaccharide or the other 1 (7%) showed changes limited to the mid-corium and deep corium. Granuloma Annulare. Hematoxylin- and eosin-

stained sections of 25 biopsy specimens from

polysaccharide-protein complex. Capillaries of the mid corium and deep coriurn contained PASpositive diastase-resistant material in the vessel walls and in some examples this substance was

25 patients with granuloma annulare were within the lumina (Fig. 12). This reaction of the capillaries was striking in necrobiosis

studied (Fig. 9). The epidermal changes consisted of a slight hyperkeratosis in 5 (20%) of the specimens, parakeratosis in 1 (4%) and slight acanthosis in 2 (8%). Areas of necrobiosis were present in all 25 specimens, but the changes were minimal in 2 (8%). The degree of the necrobiotic changes present varied from minimal to prominent. Fragmented nuclei were

lipoidica diabeticorum, and less common and less

pronounced in necrobiosis lipoidica and granulorna annulare. The basophilic staining material in areas of necrobiosis was alcian blue positive at pH 2.5 and negative at pH 0.4, and colloidal iron positive and hyaluronidase-labile. These

results indicate that the mucinous substance occasionally present in the areas of necrobiosis. is hyaluronic acid. The reactions were more

Basophilic staining material in the necrobiotic areas was observed in 20 (80%) of the specimens. Palisading of fibrocytic and epithelioid cells about necrobiotic areas was well developed

pronounced and consistently positive in granu-

thelial proliferation and thickening of the

lorna annulare.

loma annulare, less in necrobiosis lipoidica

diabeticorum and least in necrobiosis lipoidica. The aldehyde-fuchsin stain revealed a decrease in 10 (40%) of the examples (Fig. 10). Pen- to absence of elastic fibers in the areas of necvascular inflammation extended throughout the robiosis (Fig. 6). Mast cells were often observed the areas of inflammation. Snook's reticulum corium and involved the subcutaneous fat, in stain showed a network of argyrophilic fibers when present. The cellular infiltrate consisted located in areas of inflammation. The areas of predominantly of lymphocytes and only a rare necrobiosis stained yellow similar to that of plasma cell was observed. Epithelioid cells and collagen with Movat's pentachrome I stain. usually only a few giant cells were noted in 13 Frozen sections for oil red 0 fat stain revealed (52%) of the specimens (Fig. 11). Tubercle formation was observed in 8 (32%) of the positive material in the areas of necrobiosis in specimens. Capillaries in the mid-corium and the tissue examined from necrobiosis lipoidica deep corium occasionally showed slight endo- diabeticorum, necrobiosis lipoidica and granuvessel walls. A prominent increase in the number of capillaries with grouping was observed

COMMENT

in 9 (36%) of the examples of granuloma

Lesions of necrobiosis lipoidica diabeticorum

annulare. The superficial coriurn, mid-corium and deep

and necrobiosis lipoidica appeared clinically identical. The present study revealed no significant differences in the age of the patients at the time of the first biopsy examination. Patients with necrobiosis lipoidica had their skin lesions for a mean of 7.9 years prior to the first biopsy examination compared to a mean

corium were all involved in 11 (65%) of 17 specimens in which the entire thickness of the corium was present. The superficial corium was involved in 1 (6%) of these 17 specimens; the superficial corium and mid-corium in 4 (24%);

and the changes were limited to the deep of 21 months in patients with necrobiosis corium in 1 (6%).

lipoidica diabeticorum. Therefore, it appears

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Fia. 9. Granuloma annulare showing areas of necrobiosis and a perivascular lymphocytic infiltrate. H & E, X 50. Fia. 10. Granuloma annulare showing an area of necrobiosis with basophilic staining substance within a necrobiotic area. Prominent palisading of the cellular infiltrate about the necrobiotic area is present. H & E, X 50.

377

NECROBIOSIS LIPOIDICA

ft I

Fw. 11. Granuloma annulare showing giant cells. H & E, >< 135 FIG. 12. Necrobiosis lipoidica diabeticorum showing PAS-positive and diastase-resistant

material in the capillary wall and lumen. PAS with diastase digestion, >< 510.

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TABLE I Comparative histo pathologic changes Histopathologic Changes

Epidermal atrophy Involvement of superficial corium and

NecjbisipLioidica

Necrobiosis Lipoidica

Granuloma Annulare

None

41% 7%

None

15%

mid corium only Mucinous substance in necrobiotic areas 58% Prominent in 37% Palisading about necrobiotic areas Prominent in 26% Plasma cells Giant cells 68% Tubercle formation 42% Capillary-endothelial proliferation and Often pronounced thickening of vessel wall changes Increased number of capillaries in mid Prominent in 50% corium and deep corium

that the oiset of the skii lesiois occurred at a slightly yonnger age in patients without diabetes. This differs from the observatiois of Rollins and Wirikelmari (11) who rioted a younger age at onset in patients with diabetes. our study, the sex iriciderice was the same

30%

18% 80% Prominent in 24% Prominent in 40% Prominent in 53% Prominent in 0% 88% 52% 71% 32% Usually slight Usually slight changes changes Prominent in 12% Prominent in 36%

in riecrobiotic areas of tissue specirneris from diabetic arid riori-diabetic patients. Promirient palisaded arrangement of inflammatory cells

about areas of riecrobiosis was observed iri specimeris removed from 37% of patients with

diabetes, as compared to 24% from patients

with orily 1 male patient in each group. Rollins without diabetes. A prominent plasma cell iriand Wirikelmari (11) rioted 43% of the patients filtrate, tubercles arid giant cells were more studied with diabetes to be males and 7% of commori in riecrobiosis lipoidica thari iri riecthe patients without diabetes to be males. robiosis lipoidica diabeticorum. Capillary-endoOur observatioris revealed definite quantita- thelial proliferatiori arid thickening of the tive histopathologic and histochemical differ- vessel wall arid groups of small blood vessels

erices between riecrobiosis lipoidica diabeti- present in the mid-corium arid deep corium corum and riecrobiosis lipoidica (Table I). were more proriouriced in riecrobiosis lipoidica Significant epidermal atrophy was noted in sec- diabeticorum as compared to the vascular tions from 7 (41%) of the specimeris of riecro- chariges in riecrobiosis lipoidica. biosis lipoidica. Sectioris of riecrobiosis lipoidica We fourid the histopathologic differerices iri diabeticorum showed rio sigriificarit epidermal riecrobiosis lipoidica diabeticorum arid riecrobichanges. Rollins and Wirikehnari (11) reported osis lipoidica to be fairly coristant, and objecrio sigriificarit differerices in the epidermis in tive determiriatiori of the preserice of abserice of riecrobiosis lipoidica diabeticorum and riecrobio- diabetes was ordinarily possible. Material from sis lipoidica, although they rioted that an oc- 1 patient with diabetes showed the pattern casiorial specimen from rioridiabetic patients usually seeri iri riecrobiosis lipoidica arid secti&ns showed a slight degree of atrophy. Our obser- from a specimeri of 1 riori-diabetic patient prevations revealed no sigriificarit differerices in the

serited the pattern of riecrobiosis lipoidica

extent rior in the locatiori of the riecrobiotic diabeticorum. The diabetic patient was a 61 areas preserit iri the diabetic and riori-diabetic year old female and the skin disease had been patients. Rollins arid Wirikelmari (11) observed preserit for 1 year. Diabetes was first detected more prominent areas of riecrobiosis iri diabetic patierits Basophilic stairiirig material, with histochemical properties of hyaluroriic acid, was observed in riecrobiotic areas from 58% of the

at the time the skin disease was diagnosed. The riori-diabetic patierit was a 53 year old female with riecrobiosis lipoidica of 4 years' duratiori arid rio laboratory evidence of diabetes mellitus. specimeris from diabetic patients and iri orily There was no family history of diabetes. 18% from riori-diabetic patients. Tfsirig selective It must be emphasized that experience gained staining technics Rollins and Wirikelman (11) by studying sectians of the 2 cutaneous disreported a general absence of mucinous material eases is riecessary iri order to histologically

NECROBIOSIS LIPOIDICA

379

differentiate the lesiois ii the diabetic aid respectively are reported. The cutaieous lesiois ioi-diabetic patieIt. Some overlap of histo- ii diabetic aid ioi-diabetic patieits are clinipathologic patteits occur aid at times the dif- cally identical but show quantitative histoferentiatioi is difficult. Biopsy examinatioi and

pathologic aid histochemical differences. Prom-

determination of the preseice of the diabetic iIeit palisading of inflammatory cells about or ioi-diabetic histopathologic pattern cai othy necrobiotic centers, mucinous material ii areas

serve as an adjuict to a complete medical of iecrobiosis, aid alterations of the capilhistory, physical examinatioi and appropriate laries ii the mid-corium and deep corium were laboratory studies. more commothy observed in iecrobiosis lipoidNecrobiosis lipoidica diabeticorum and iec- ica diabeticorum. Epidermal atrophy, giant robiosis lipoidica may represent 2 different dis- cells, tubercle formatioi and a prominent ease processes, but the ideitical clithcal pic- plasma cell infiltrate were observed more oftei ture, similar clinical course aid overlapping of ii necrobiosis lipoidica. Histopathologic differhistopathologic features indicate that the 2 coi'- entiatioi of the cutaneous lesions in the diaditiops probably represent the same basic proc- betic or potential diabetic patient from the ess. The histopathologic differeices observed are irnn-diabetic patient can usually be made. Exprobably due to factors ii the host response of ceptiois to the usual histopathologic pattern diabetic or potential diabetic patients aid non- occur aid microscopic differeitiation does not diabetic patients. The chaiges noted in the replace the medical history, physical examinacapillaries in necrobiosis lipoidica diabeticorum tioi and appropriate laboratory tests, but cai are known to occur ii the skin (17—19) and serve as ai important adjuict in evaluating other orgai systems ii patients with diabetes the patient's disease. (10, 20, 21). Alteratiois ii the compositioi of REFERENCES serum proteins have beei reported ii patieits 1. tJrbach, E.: Beitrage zu einer physiologischen with diabetes and are thought to play a role und pathologischen Chemie der Haut: X. Mitteilung. Eine neue diabetische Stoffii the development of the vascular changes (10, 22). It is probable that granulomatosis disciformis

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2. Oppenheim, M.: TJber eine bisher nicht

Meischer aid Leder (23) and necrobiosis lipoidica are the same disease process (11). A number of extensive studies of granuloma

tose bei Diabetes mellitus (Dermatitis

airnulare have been reported (7, 24—26) and comparisons of microscopic features with necrobiosis lipoidica have also beei made (7, 26— 27). The histo pathologic changes present in graiuloma aimulare closely resemble those seen ii iecrobiosis lipoidica diabeticorum, aid histopathologic differentiatian betweei the two may not be possible (Table I). The more common

superficial involvement of the corium and mucinous material ii areas of necrobiosis ii grarniloma airnulare were features of value ii making a histopathologic differentiatioi from iwcrobiosis lipoidica diabeticorum. Aiother dif-

ferential feature was the pronouiced capillary change ii the mid-corium aM deep corium in necrobiosis lipoidica diabeticorum.

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