Identification of Basic Patterns - Skin - Nodular and Diffuse Dermatitis

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Identification of Basic Patterns: Skin: Nodular and Diffuse Dermatitis
See Fig. 5.174 A&B.
Figure 5.174: A&B. Nodular dermatitis and diffuse dermatitis.
Nodular dermatitis is distinguished from perivascular dermatitis (see Fig. 5.16 A&B) by the density of the infiltrate of inflammatory cells.
In the perivascular dermatitides, the infiltrates can be described roughly as being sparse to moderately dense, whereas in nodular
dermatitides the infiltrates are dense, i.e., they form nodules many times more replete with cells than are the infiltrates of a perivascular
dermatitis. The nodules, just like their much less robust counterparts in perivascular dermatitis, are centered around venules, usually
throughout the reticular dermis (Fig. 5.175 A&B), but sometimes also in septa of the subcutaneous fat and at other times restricted to the
upper part of the dermis (Fig. 5.176 A&B). Very often, endothelial cells of venules in nodular dermatitides are plump, as they may be in
any inflammatory disease; no significance for diagnosis should be attached to "swollen" endothelial cells. In short, nodular dermatitis is a
caricature of perivascular dermatitis, one that tends to be both superficial and deep, but, at times, is superficial mostly. As was stated
previously in regard to a "bottom heavy" infiltrate of lymphocytes of a perivascular "dermatitis," especially one that also affects the
subcutaneous fat, a nodular "dermatitis" of lymphocytes that is distinctly "bottom-heavy" almost certainly is not a dermatitis but a
lymphoma.
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Figure 5.175: A&B. A nodule made up of epithelioid histiocytes: sarcoidosis. The nodular infiltrate throughout the dermis and
in subcutaneous fat is composed mostly of epithelioid histiocytes, which qualifies this process as granulomatous, the actual
disease being sarcoidosis.
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Figure 5.176: A&B. A nodule made up of epithelioid histiocytes: lichen nitidus. A nodule, in this instance composed mostly of
epithelioid histiocytes and, therefore, granulomatous, may be confined to the upper part of the dermis, as in this example of
lichen nitidus.
Although, as a rule, nodular dermatitis is characterized by notable collections of inflammatory cells—lymphocytes alone (Fig. 5.177 A&B),
epithelioid histiocytes alone (Fig. 5.178 A&B), or epithelioid histiocytes surrounded by lymphocytes and/or plasma cells (Fig. 5.179 A&B)
and, episodically, neutrophils mostly. On occasion a nodular dermatitis (or panniculitis) may consist of but a single large nodule made up
of neutrophils almost exclusively (an abscess) (Fig. 5.180 A&B) or of smaller nodules made up mostly of neutrophils (Fig. 5.181 A&B). At
times, a nodular dermatitis (or panniculitis) may be formed of epithelioid histiocytes mostly (a granuloma) (Fig. 5.182 A&B) or a
mixed-cell infiltrate punctuated by large foamy histiocytes with predilection for emperipolesis (Fig. 5.183 A&B), that is, Destombes-Rosai-
Dorfman disease. In one particular circumstance, a nodule is very small and very superficial, the stereotype of that unique presentation
being lichen nitidus which first is recognizable histopathologically as a nodule formed mostly of lymphocytes in a focus in the uppermost
part of the dermis (Fig. 5.184 A&B), progresses to a but slightly larger collection composed of both lymphocytes and epithelioid
histiocytes (Fig. 5.185 A&B), and reaches its apogee, while still remaining rather small, as an aggregation (Fig. 5.186 A&B) constituted
of epithelioid histiocytes overwhelmingly.
Figure 5.177: A&B. Nodules made up of lymphocytes: lymphocytoma cutis. The nodules throughout the dermis and in the
upper part of the subcutaneous fat are composed nearly entirely of lymphocytes, lymphoid follicles being formed by some of
them. When the cause of an inflammatory process with these particular attributes morphologic is not known, as was the
situation here, the name given to it is "lymphocytoma cutis."
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Figure 5.178: A&B. Sarcoidal granuloma in sarcoidosis. Nodules composed entirely of epithelioid histiocytes, devoid of
lymphocytes and plasma cells, are findings expected in a stereotypical example of sarcoidosis such as this one.
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Figure 5.179: A&B. Tuberculoid granuloma in tuberculoid leprosy. Nodules composed of epithelioid histiocytes enveloped by
lymphocytes and plasma cells are findings expected in a variety of infectious processes, including lupus vulgaris, the
recidivans form of leishmaniasis, and tuberculoid leprosy, the latter being the diagnosis here.
Figure 5.180: A&B. A nodule formed by an abscess. A nodule constituted entirely of neutrophils is an abscess, in this instance
brought into being by rupture of an infundibular cyst, the cornified cells (squames) of which are evident among the
neutrophils.
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Figure 5.181: A&B. Nodules made up mostly of neutrophils: dermatophytosis (Majocchi's granuloma). Some of the nodules
composed of polymorphonuclear leukocytes are punctuated by a hair that contains dermatophytic hyphae, thereby
establishing the condition as a manifestation of Majocchi's granuloma relatively early in the course of it.
Figure 5.182: A&B. A nodule in the form of a foreign body granuloma. This large solitary nodule represents a foreign body
reaction consequent to rupture of an infundibular cyst, the cornified contents of which were expelled and now are surrounded
by epithelioid histiocytes, many of them multinucleate.
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Figure 5.183: A&B. A nodule composed of a distinctive mixture of inflammatory cells: Destombes-Rosai-Dorfman disease. In
the nodule is a potpourri of inflammatory cells, among them large foamy histiocytes with an inclination irrepressibly to
emperipolesis. The nodule pictured is characteristic of Destombes-Rosai-Dorfman disease and is a pattern so singular
histopathologically that it can be recognized at scanning magnification, as is the case here.
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Figure 5.184: A&B. Life of a nodule (early): lichen nitidus. The nodule made up mostly of lymphocytes joined by relatively few
histiocytes presented itself as a papule of lichen nitidus at an early stage of that process.
Figure 5.185: A&B. Life of a nodule (fully developed): lichen nitidus. The nodule composed of epithelioid histiocytes and
lymphocytes in almost equal numbers formed a papule of lichen nitidus at a stage more advanced than that pictured in Figure
5.184.
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Figure 5.186: A&B. Life of a nodule (late): lichen nitidus. The nodule that consists almost entirely of epithelioid histiocytes is
representative of a papule of lichen nitidus at a stage still later than that shown in Figure 5.185.
Infiltrates that make up nodules in nodular dermatitis, such as those that form a solitary large aggregation, may be monomorphous or
polymorphous, i.e., mixed. A monomorphous infiltrate of neutrophils in a discrete collection and associated often with signs of destruction
of tissue is that of an abscess; a nodule composed of epithelioid histiocytes is a granuloma. When a granuloma is unaffiliated with a
readily discernible infiltrate of lymphocytes (and, at times, plasma cells), designated, memorably, "naked tubercle," it is considered to be
"sarcoidal" (Fig. 5.187), and when a granuloma is encircled by a mantle of lymphocytes (and sometimes plasma cells), it is deemed to be
"tuberculoid" (Fig. 5.188). A granuloma in which epithelioid histiocytes are arranged in the manner of a fence of stakes like that
constructed for defense militarily is called "palisaded" (Fig. 5.189) (the "palisaded" histiocytes representing a "reaction" to various
"foreign bodies" that range from degenerated collagen [e.g., in necrobiosis lipoidica] to fibrin [e.g., in rheumatoid nodule], the changes in
the center of a palisade presumably resulting from a "mini-infarct"), and one in which epithelioid histiocytes appear to be splayed
between bundles of collagen is termed "interstitial" (Fig. 5.190). A granuloma joined by neutrophils in number (Fig. 5.191), or even a
single cluster of them, is regarded as "suppurative." A granuloma in which epithelioid histiocytes have engulfed matter extraneous to a
given tissue is called "foreign body," but the term "foreign body granuloma" communicates cause only; the pattern of it may be "sarcoidal"
(Fig. 5.192), "tuberculoid," "palisaded" (Fig. 5.193 A&B), "interstitial," or "suppurative." The commonest granulomatous dermatitis, which
happens also to be a "foreign body reaction," results from rupture of an infundibular cyst, the contents of it having been spewed into the
dermis (Fig. 5.194 A&B). Paradoxically, sarcoidosis may present itself as tuberculoid granulomas (Fig. 5.195 A&B). Parenthetically, no
specificity is conveyed by any of the "types" of multinucleate histiocytic giant cells such as foreign body, Langhans', and Touton. That
which is said to be a foreign body or a Langhans' giant cell often is the very same kind of multinucleate histiocyte whose appearance
varies because of where and at what angle it was traversed by the blade of a microtome. What is called a Touton giant cell, named for a
German pathologist of the 19th century who first described it, may be encountered in such dissimilar conditions as dermatofibroma and
malignant fibrous histiocytoma, not only in "juvenile xanthogranuloma."
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Figure 5.187: Sarcoidal granuloma. A collection such as this one of epithelioid histiocytes devoid of lymphocytes and plasma
cells qualifies as a "sarcoidal granuloma," known colloquially as a "naked tubercle."
Figure 5.188: Tuberculoid granuloma. A collection such as this one of epithelioid histiocytes surrounded by numerous
lymphocytes and plasma cells is termed a "tuberculoid granuloma."
Figure 5.189: Palisaded granuloma. Epithelioid histiocytes aligned in a palisade around a zone that contains mucin, a tad of
fibrin, and some degenerated collagen constitute a type of granuloma referred to as "palisaded."
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Figure 5.190: Interstitial granuloma. Epithelioid histiocytes insinuated between bundles of collagen make up a type of
granuloma named "interstitial."
Figure 5.191: Suppurative granuloma. The combination of collections of epithelioid histiocytes and of neutrophils, no matter
the number of those polymorphs, constitutes a "suppurative granuloma."
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Figure 5.192: A&B. Foreign body granuloma, sarcoidal. This sarcoidal granulomatous dermatitis is "foreign body" in type, the
cause being pellets of metal that contain iron, that material being highlighted by polarized light.
Figure 5.193: A&B. Foreign body granuloma, palisaded. The palisaded granulomatous dermatitis is "foreign body" in type, the
cause being crystals of gout that were lost in the preparation of the specimen en route to sectioning of it, the blue-gray
material in the center of the palisade being proteinaceous matrix.
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Figure 5.194: A&B. Foreign body granuloma, sarcoidal. A nodule of epithelioid histiocytes, many of them multinucleate, within
which are clefts that previously housed cholesterol, some of those spaces now containing one or more squames, is diagnostic
of granulomatous inflammation secondary to rupture of an infundibular cyst. Because the granuloma is made up nearly
entirely of epithelioid histiocytes, it qualifies as sarcoidal.
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Figure 5.195: A&B. Tuberculoid granulomas in sarcoidosis. This quintessential example of tuberculoid granulomatous
inflammation, characterized as it is by collections of epithelioid histiocytes surrounded by formidable numbers of
lymphocytes, in this instance happens to be an expression of sarcoidosis. In short, sarcoidosis, stereotypically, consists of
sarcoidal granulomas, but, at times, of tuberculoid ones.
At times, a nodular and/or diffuse infiltrate of mycosis fungoides may be punctuated by zones of granulomatous inflammation, that
circumstance being termed, misleadingly, "granulomatous mycosis fungoides" (Fig. 5.196 A&B); the mycosis fungoides is not
granulomatous, but rather that lymphoma has been joined by granulomatous inflammation. The influx of epithelioid histiocytes, some of
them multinucleate often, into a lesion of mycosis fungoides is consequent to the effects of products of neoplastic lymphocytes on elastic
fibers, those fibers becoming altered and serving as "foreign bodies" that then induce a granulomatous response. In the caricature of that
scenario, namely, "granulomatous slack skin" (another misnomer for mycosis fungoides with associated granulomatous inflammation),
elastic fibers, many of them seen to be calcified in sections of some specimens, are noted to be lodged in the cytoplasm of multinucleate
histiocytes (the extraordinary number of nuclei of those histiocytes tending to be riveting). A clue to diagnosis of this special presentation
of mycosis fungoides, namely, that affiliated with extensive granulomatous inflammation, is the observation, at scanning magnification, of
a dense patchy infiltrate of lymphocytes distributed more haphazardly than in any authentic granulomatous inflammatory disease.
Figure 5.196: A&B. Secondary granulomatous inflammation: A pitfall in diagnosis of a nodular infiltrate of mycosis fungoides.
Because the granulomatous inflammation is so striking, the entire process pictured could be misread as non-neoplastic. Even
at scanning power, however, the patchy infiltrate of lymphocytes throughout the dermis and in the uppermost part of the
subcutaneous fat should alert to the possibility of this process, fundamentally, being mycosis fungoides.
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When small lymphocytes predominate in a nodular dermatitis, particularly one that is "top heavy," but in which the entire reticular dermis
and the upper part of the subcutaneous fat may be caught up in the process, the condition is referred to by a variety of names, among
those being "lymphocytoma cutis" (see Fig. 5.177 A&B), which is the one we employ when no cause is demonstrable, and
"lymphadenosis benigna cutis" when the cause is shown to be Borrelia burgdorferi. An ill-advised generic term for changes like those just
described, and one that should be eschewed scrupulously, is "pseudolymphoma," a word and concept that lacks specificity in all
respects. In every instance of a nodular infiltrate composed mostly of small lymphocytes, an effort must be made deliberately to
recognize the individuality of it and to diagnose it with specificity in the language of dermatology. For example, a wedge-shaped nodular
infiltrate composed mostly of lymphocytes, but also of numerous eosinophils, should be diagnosed, with precision, for what it is, to wit, a
response to a bite of a tick (Fig. 5.197 A&B). In some instances, an infiltrate that takes the form of nodules is mixed, i.e., in addition to
the preponderant small lymphocytes, there may be various combinations, and quantities, of larger lymphocytes, plasma cells, and
eosinophils, as is the case in nodular scabies (Fig. 5.198). Not uncommonly in that particular manifestation of scabies in which no sign of
the mite, her progeny, or her detritus is apparent in the stratum corneum, large lymphocytes, as well as small ones, are represented. It is
important that a histopathologist not "overcall" the changes in nodular scabies "lymphomatoid papulosis" because of the presence of
large lymphocytes in the nodular mixed-cell infiltrate; unlike the situation in nodular scabies, the large lymphocytes in lymphomatoid
papulosis (Fig. 5.199) are decidedly atypical, that is, the nuclei not only are large but distinctly pleomorphic, and some of them usually
are in mitosis. The inclination to "over-read" slightly large lymphocytes as being those of lymphoma led coworkers to the conclusion
erroneously that a longstanding photoallergic dermatitis ("persistent light eruption") on which had been imposed signs of lichen simplex
chronicus might be a neoplastic process they termed "actinic reticuloid," "reticulosis" in those years being employed as a synonym for
lymphoma (Fig. 5.200 A&B).
Figure 5.197: A&B. Response to the "bite" of a tick, not "pseudolymphoma." At scanning magnification, the findings can be
told to be those of an inflammatory process, rather than a lymphomatous one, because the infiltrate is wedge-shaped,
"top-heavy," made up mostly of small lymphocytes, and, at the center of the lesion, associated with pseudocarcinomatous
proliferation, these findings being a response to a tick "bite." At high power are many eosinophils.
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Figure 5.198: A&B. Nodular scabies, not "pseudolymphoma." At scanning magnification, the infiltrate can be told to be that of
an inflammatory, rather than of a lymphomatous, process by virtue of the wedge shape of it and the focus of spongiosis in the
center of it. At higher magnification, the infiltrate is seen to be made up of small and large lymphocytes, as well as many
eosinophils. The atypia of the lymphocytes is not nearly enough to prompt consideration of lymphomatoid papulosis or any
other lymphoma.
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Figure 5.199: A&B. Lymphomatoid papulosis, not "pseudolymphoma." Although the "top-heavy" nodular infiltrate shown here
is somewhat wedge-shaped, it is not that of a response to the "bite" of a tick because atypical lymphocytes predominate
compellingly over small lymphocytes and no eosinophils are accompanying. In short, these are the findings of one of many
expressions of lymphomatoid papulosis, a CD 30 lymphoma.
Figure 5.200: A&B. Psoriasiform nodular dermatitis: actinic reticuloid. This pattern, namely, psoriasiform nodular, is
uncommon and should call to mind a longstanding photoallergic dermatitis complicated by the effects of persistent rubbing
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(lichen simplex chronicus), a condition designated "actinic reticuloid" because it was thought by those who described it first
to resemble a "reticulosis" (lymphoma), consisting as it does of a few large lymphocytes in a mixed-cell infiltrate of small
lymphocytes, plasma cells, and eosinophils.
Two snares are worthy of note in regard to nodular infiltrates of lymphocytes: (1) At times, epithelioid histiocytes predominate in a locus
of nodular infiltration by lymphocytes in what otherwise would be deemed, reflexly, to be lymphocytoma cutis, that particular finding of
epithelioid histiocytes in a collection, no matter whether solitary and small, qualifying the process as being granulomatous of tuberculoid
type (Fig. 5.201 A&B). (2) A pure population of small lymphocytes in nodular array may be a manifestation of chronic lymphocytic
leukemia or of the lymphomatous analogue of it (Fig. 5.202 A&B).
Figure 5.201: A&B. Granulomatous dermatitis, not "pseudolymphoma." At scanning power, a "top-heavy" nodular infiltrate
seemingly made up of lymphocytes only could be construed as what is termed, conventionally, "pseudolymphoma,"
"lymphocytoma cutis," and "cutaneous lymphoid hyperplasia." At higher power, however, it becomes apparent that, in at least
one locus, epithelioid histiocytes predominate, making this granulomatous.
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Figure 5.202: A&B. Leukemia cutis, not "pseudolymphoma." This "top-heavy" nodular infiltrate of monomorphous lymphocytes
is that of chronic lymphocytic leukemia.
Acknowledgment must be made here frankly that the criteria in vogue for distinguishing what, at the time of publication of the first edition
of this work in 1978, and even at the time of the second edition in 1997, was called, nearly universally, pseudolymphoma from authentic
lymphoma, are passé because they were wrong. In those days, it was believed, we among the believers, that a "pseudolymphoma"
differed from true lymphoma by being "top heavy," sparing epithelial structures of adnexa, consisting of a mixed-cell infiltrate, exhibiting
"tingible bodies" (nuclear "dust" of lymphocytes) in germinal centers of lymphoid follicles, and being composed mostly of small
lymphocytes. Each of those five criteria are flawed irreparably. As but one example of such serious limitation is that encountered in a
slightly raised papule of a B-cell lymphoma, namely, a nodular infiltrate of lymphocytes that is "top heavy" (Fig. 5.203 A&B). Nonetheless,
a decidedly "bottom-heavy" infiltrate made up of lymphocytes, for practical purposes, is lymphoma (Fig. 5.204 A&B). In general,
irrespective of the architectural pattern or the makeup of a nodular (or diffuse) infiltrate of lymphocytes mostly, a requisite for diagnosis
of lymphoma is predominance, in some high-power fields, of lymphocytes whose nucleus is unquestionably atypical. That situation does
not obtain in a nodular infiltrate of an inflammatory disease. But just as atypical melanocytes are not a province of melanoma alone, they
being found in various nevi, Spitz's nevus being the prime example of that, so, too, it is for atypical lymphocytes, which not only are seen
in lymphomas, but may be met with in a lymphomatoid inflammatory process, such as a drug eruption, and in an infiltrate generated in
response to infection by herpesvirus, not necessarily one concurrent with a vesicle of that eruption, but in a papule prodromal to it and
devoid of any of the usual cytopathic effects of the virus. In the latter circumstances, however, the infiltrates that house atypical
lymphocytes are not usually nodular and diffuse.
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Figure 5.203: A&B. Lymphoma, not "pseudolymphoma." A "top-heavy" infiltrate of lymphocytes does not militate against
lymphoma! Just because this dense infiltrate of lymphocytes is "top-heavy" does not mean that it is an inflammatory process
that simulates a lymphoma. Scrutiny of attributes cytopathologic of lymphocytes reveals each of them to have a decidedly
atypical nucleus whose outline is convoluted, diagnostic of lymphoma.
Figure 5.204: A&B. Lymphoma, not "pseudolymphoma." A "bottom-heavy" infiltrate of lymphocytes nearly always signifies
lymphoma! These photomicrographs were published in the second edition as an example of "pseudolymphoma." That
diagnosis was wrong. The "bottom-heavy" character of the infiltrate, ill-defined aggregations of pale cells that are not true
germinal centers, and predominance of atypical lymphocytes in many loci make this lymphoma.
The emphasis in this endeavor devoted to diagnosis with specificity of inflammatory skin diseases is on analysis of patterns formed by
cells, rather than on attributes cytopathologic. That, however, in no way is meant to minimize the importance of paying attention carefully
to characteristics cytopathologic, especially in certain situations, among those being the changes wrought in nuclei by the viruses of
herpes and cytomegalic inclusion disease, and by whatever is responsible for the findings that give to nuclei of lymphocytes of
lymphomatoid papulosis and of Langerhans' cells of histiocytosis X a distinctiveness so special that diagnosis of those diseases cannot
be accomplished without notice having been taken of them.
The stereotypical example of a nodular dermatitis with predominance of neutrophils is Sweet's syndrome (Fig. 5.205 A&B), which may be
simulated histopathologically by bowel-bypass syndrome and one of the presentations of pyoderma gangrenosum (Fig. 5.206 A&B).
Sometimes mononuclear cells that, in fact, are immature neutrophils, outnumber mature neutrophils in Sweet's syndrome, they being an
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indication that the "syndrome" in that particular patient is an expression of granulocytic leukemia. Although scattered particles of nuclei of
neutrophils, i.e., nuclear "dust," may be abundant in Sweet's syndrome, no signs are detectable of indubitable vasculitis of small vessels,
to wit, fibrin in the wall of venules and/or thrombi within lumen of them. Signs of leukocytoclastic vasculitis in a nodular dermatitis, namely,
fibrin in the wall of venules and nuclear "dust" of neutrophils, in conjunction with eosinophils, plasma cells, and lymphocytes, are indicative
of granuloma faciale (if the biopsy specimen came from a face) (Fig. 5.207 A&B) or erythema elevatum diutinum (if the biopsy specimen
was taken from an extremity). As may be inferred from that peculiarity in nomenclature, granuloma faciale and erythema elevatum
diutinum are two names for a single pathologic process situated on different anatomic sites, that process, fundamentally, being a
longstanding leukocytoclastic vasculitis and not granulomatous.
Figure 5.205: A&B. Nodular dermatitis of Sweet's syndrome. The nodular infiltrate of neutrophils can be told at scanning
magnification to be that of Sweet's syndrome (or its sometimes lookalike, pyoderma gangrenosum) and not that of granuloma
faciale by virtue of the extensive edema of the papillary dermis. At higher magnification, the extraordinary quantity of nuclear
"dust" of neutrophils also is in favor of Sweet's syndrome.
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Figure 5.206: A&B. Nodular dermatitis of pyoderma gangrenosum. The nodular infiltrate of neutrophils of pyoderma
gangrenosum is marked by edema of the papillary dermis, as was the case, too, for the example of Sweet's syndrome pictured
in Figure 5.205. In this instance, however, neutrophils are mostly intact; nuclear "dust" is scant.
Figure 5.207: A&B. Nodular dermatitis of granuloma faciale. Nodules in the upper half of the dermis composed of a potpourri
of inflammatory cells, neutrophils and nuclear "dust" of them included, as well as a hint of fibrin in the wall of a venule, are
signs diagnostic of granuloma faciale when the lesion is on the face and of erythema elevatum diutinum when on an extremity.
Although nuclear "dust" of inflammatory cells in diseases of skin (and subcutaneous fat) usually derives from fragmentation (karyorrhexis)
of nuclei of neutrophils (Fig. 5.208 A&B), at times disintegration of nuclei of lymphocytes (Fig. 5.209 A&B) is observed in sections of
tissue of diseases as unalike as lymphocytoma cutis and lupus profundus.
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Figure 5.208: A&B. Differential diagnosis of a superficial infiltrate of neutrophils and nuclear "dust" of them: "early" Sweet's
syndrome versus leukocytoclastic vasculitis. Sweet's syndrome, even at an early stage of it, is distinguishable
histopathologically from leukocytoclastic vasculitis by the density of the superficial infiltrate pictured here and the
extraordinary amount of nuclear "dust" of neutrophils.
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Figure 5.209: A&B. Nuclear "dust" of lymphocytes: no more specific than nuclear "dust" of neutrophils, but an expected
accompaniment of lupus profundus. Lupus profundus is nothing other than discoid lupus erythematosus that affects the
subcutaneous fat, usually in addition to involvement of the reticular dermis and, not uncommonly, the dermoepidermal
junction and epidermis. The patchy lymphoplasmacytic infiltrate characteristic of a fully developed lesion of lupus profundus
almost always is joined by nuclear "dust" of lymphocytes, as is shown here.
"Diffuse dermatitis" may evolve from confluence of nodules or become a sheet of inflammatory cells seemingly from near the outset, and,
just as is the case for nodular dermatitis, diffuse dermatitis may be restricted to the upper half of the dermis, extend throughout the entire
width of the dermis, and, in some instances, affect septa, and even lobules, in the subcutaneous fat.
When a bandlike infiltrate, continuous or discontinuous, i.e., patchy, is present in the upper part of the dermis, as exemplified by
acrodermatitis chronica atrophicans and nodular scabies, it may be difficult to decide whether it qualifies as "lichenoid" or "superficial
diffuse." In short, no crisp boundary exists between "lichenoid dermatitis" and "superficial diffuse dermatitis," as is so, too, for
"perivascular dermatitis" and "nodular dermatitis"; it is not possible, with utter repeatability, to state where one ends and the other
begins. Confluence of nodules occurs, for example, in Sweet's syndrome (see Fig. 5.205), in nodular scabies (see Fig. 5.198), and,
episodically, in lymphocytoma cutis, as well as in a lymphoma such as mycosis fungoides (see Fig. 5.196). Dense infiltrates arranged
diffusely throughout the reticular dermis, without formation first of nodules perceptible overtly, may consist entirely of neutrophils, as in
rheumatoid neutrophilic dermatitis; of lymphocytes, as in lymphocytoma cutis; of plasma cells mostly, as in some infectious processes,
like acrodermatitis chronica atrophicans; of plasma cells, lymphocytes, nonepithelioid histiocytes (macrophages), and, at times, a
smattering of neutrophils in acute leishmaniasis (Fig. 5.210 A&B); of foamy histiocytes mostly, as in noninfectious conditions such as
xanthogranuloma (Fig. 5.211 A&B), and in infectious processes, such as lepromatous leprosy or infection by atypical mycobacteria (Fig.
5.212 A&B). A dense diffuse infiltrate made up nearly exclusively of abnormal lymphocytes occurs in a lymphoma or a leukemia,
malignant neoplasms, and of mast cells in the juvenile (nodular) type of urticaria pigmentosa (Fig. 5.213 A&B), a benign neoplasm. A
dense diffuse mixed-cell infiltrate of abnormal Langerhans' cells, eosinophils, neutrophils, lymphocytes, and plasma cells appears in that
expression of histiocytosis X known as Hand-Schüller-Christian disease, presumably a benign neoplastic process (Fig. 5.214 A&B).
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Figure 5.210: A&B. Specific diagnosis of a diffuse dermatitis: leishmaniasis, acute. This dense diffuse dermatitis made up
mostly of histiocytes, but also of scattered lymphocytes, can be identified as that of acute leishmaniasis by dot-like organisms
visible in the cytoplasm of macrophages.
Figure 5.211: A&B. Specific diagnosis of a diffuse dermatitis: xanthogranuloma. This dense diffuse dermatitis can be
recognized as that of xanthogranuloma because it is composed of innumerable foamy histiocytes, many of which are
multinucleate of Touton type.
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Figure 5.212: A&B. Specific diagnosis of a diffuse dermatitis may require a specialized stain: atypical mycobacteria revealed by
Fite stain in a patient immunosuppressed. This dense diffuse dermatitis made up mostly of histiocytes, among which
lymphocytes are scattered, can be suspected of being mycobacterial in cause because of the grayish hue of cytoplasm of
macrophages. The specialized stain reveals countless organisms.
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Figure 5.213: A&B. Specific diagnosis of a dense, diffuse infiltrate of a non-inflammatory disease: urticaria pigmentosa. This
dense diffuse infiltrate of mononuclear cells can be told to be that of urticaria pigmentosa because each one of them is a mast
cell.
Figure 5.214: A&B. Specific diagnosis of a dense, diffuse infiltrate of a non-inflammatory disease: Hand-Schüller-Christian
disease. The large, pale-staining, bean-shaped nuclei and the abundant amphophilic cytoplasm of the cells that dominate this
dense, diffuse infiltrate establish them as Langerhans' cells and the diagnosis as Hand-Schüller-Christian disease. The
abnormal Langerhans' cells are positive for S-100 protein.
Two extraordinary hazards are presented by dense diffuse infiltrates of xanthogranuloma at different stages of that inflammatory
process. The first is the incredibly inviting trap posed at a very early stage when the cells that make up the infiltrate display oval nuclei
that are crowded because cytoplasm is so scant, the histiocytes not yet having become lipidized, and many of the nuclei of them being in
mitosis (Fig. 5.215 A&B). It is easy to misread those changes as ones of a malignant neoplasm, especially a sarcoma. Clues to the
correct diagnosis are recognition of a hint of foamy cytoplasm in any cell, the presence of scattered eosinophils, lymphocytes, plasma
cells, and, sometimes, neutrophils, and the monomorphous quality of the nuclei of the histiocytes themselves. Even at a slightly later
stage when histiocytes have become lipidized overtly, a xanthogranuloma still may be misread as a malignant fibrous histiocytoma
because nuclei of them may be large, heterochromatic, and pleomorphic, and some may be in mitosis (Fig. 5.216 A&B). The second lure
is the finding of "monster cells," like those of dermatofibroma during the macrophagic stage of that latter inflammatory process (Fig.
5.217 A&B), in foamy histiocytes of xanthogranuloma when a lesion of it still is evolving. That phenomenon can be misinterpreted easily
as malignant fibrous histiocytoma. Clues that enable the inflammatory process to be distinguished from the malignant neoplastic one are
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far fewer mitotic figures, the virtual absence of abnormal mitotic figures, and eosinophils, lymphocytes, plasma cells, and, at times,
neutrophils sprinkled among the lipidized histiocytes.
Figure 5.215: A&B. Specific diagnosis of a diffuse dermatitis: xanthogranuloma. This dense diffuse dermatitis could be
misconstrued as a neoplastic process, even a sarcoma, because oval nuclei of cells are crowded and somewhat pleomorphic.
In fact, the changes are typical of xanthogranuloma at an early stage of that process, that is, before histiocytes have become
lipidized.
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Figure 5.216: A&B. Dense diffuse dermatitis that may simulate a malignant neoplasm: xanthogranuloma. This dense diffuse
infiltrate could be misinterpreted as that of a sarcoma because nuclei are atypical and mitotic figures are spotted readily. In
actuality, this is a xanthogranuloma at a stage later than that pictured in Figure 5.215, the evidence for that being the foamy
cytoplasm of histiocytes. The ulcer is secondary to trauma.
Figure 5.217: A&B. Specific diagnosis of a diffuse dermatitis: dermatofibroma. This dense diffuse fibrosing dermatitis (and
panniculitis) can be told to be a dermatofibroma because plump oval fibrocytes, arranged haphazardly, are associated with
coarse bundles of collagen arrayed randomly. Moreover, the epidermis is acanthotic. The finding of strikingly atypical nuclei of
mesenchymal cells prompted the name "dermatofibroma with 'monster' cells."
The finding of cells with startling nuclear atypia, as is the case for "monster cells," does not exclude an inflammatory disease from
consideration for diagnosis histopathologic, any more than does absence totally of nuclear atypia, as is the case invariably for
dermatofibrosarcoma protuberans, eliminate from consideration a malignant neoplasm.
The following algorithm is designed to lead histopathologists to specific diagnosis of nodular and diffuse dermatitides:
ALGORITHM: Nodular and Diffuse Dermatitis
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Identification of Basic Patterns - Skin - Nodular and Diffuse Dermatitis

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Identification of Basic Patterns: Skin: Nodular and Diffuse Dermatitis

See Fig. 5.174 A&B.

Figure 5.174: A&B. Nodular dermatitis and diffuse dermatitis.

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ALGORITHM: Nodular and Diffuse Dermatitis

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