Keloid vs. Hypertrophic scar

Differential Diagnosis

Keloid Hypertrophic Scar 1. Lesion usually elevated markedly above the skin surface; little tendency to regression without therapy 1. Lesion elevated slightly above the skin surface; even without treatment, tends, in time, to become flush with the surface of the skin or depressed below it as an atrophic scar 2. No subepidermal clefts or vesicles 2. Subepidermal clefts or vesicles form occasionally 3. Markedly thickened bundles of collagen with few fibrillary ones in a lesion developed fully 3. Fibrillary bundles of collagen only; no markedly thickened ones 4. Collagen bundles brightly eosinophilic 4. Collagen bundles slightly eosinophilic or amphophilic 5. Collagen bundles in haphazard array 5. Collagen bundles generally oriented parallel to the surface of the skin 6. Plump oval fibrocytes alongside thickened collagen bundles also arrayed in haphazard pattern 6. Oval fibrocytes alongside fibrillary bundles of collagen arranged mostly parallel to the skin surface 7. Widely dilated blood vessels oriented randomly 7. Widely dilated blood vessels oriented somewhat perpendicular to the skin surface 8. Abundant mucin between bundles of collagen often, especially in an early lesion 8. Little mucin between bundles of collagen except in an early lesion when it may be copious 9. Infiltrates of lymphocytes around dilated blood vessels at the periphery of a lesion especially 9. Infiltrates of lymphocytes around dilated blood vessels throughout a lesion

Discussion

Keloids and hypertrophic scars have many findings histopathologic in common (e.g., fibroplasia, telangiectases, infiltrates of inflammatory cells, mucin) and, in some instances, attributes of what seem to be both keloid and hypertrophic scar may be found together in sections from the same biopsy specimen. Almost always such a lesion turns out to be a keloid early in the course of development, i.e., prior to the appearance of thick bundles of collagen. When distinct, brightly eosinophilic, thick bundles of collagen are arrayed haphazardly in a lesion made up entirely of fibroplasia, the diagnosis, by convention, is keloid. No such bundles of collagen are found in a hypertrophic scar.

Hypertrophic scars usually are linear lesions that follow trauma such as those of a surgical incision and an accidental laceration. The scars have no predilection for individuals with any particular intensity of pigmentation, unlike the situation for keloids whose proclivity is for dark-skinned individuals. As a rule, hypertrophic scars tend to flatten without treatment, a process that takes years, whereas keloids do not shrink appreciably on their own.

Both keloids and hypertrophic scars are types of fibrosing dermatitis, i.e., inflammatory processes that resolve with fibroplasia. The entire spectrum of inflammation from granulation tissue to sclerosis may be found in keloids and hypertrophic scars depending on when in their course a biopsy specimen is obtained.

In an early lesion of a keloid, only abundant fibrillary bundles of collagen are present in nodular aggregations that contain numerous plump fibrocytes in random array. No brightly eosinophilic thickened bundles of collagen are found in an early keloid. The clue most valuable to diagnosis of a keloid, even at this early stage, is the presence of fibrillary bundles of collagen like those of a scar but in a lesion whose configuration is distinctly nodular. In time, foci of brightly eosinophilic, markedly thickened collagen bundles arranged haphazardly appear in the mass of fibrillary bundles of collagen. Those thickened bundles of collagen, in that particular setting, are signs of a keloid. The diagnosis histopathologic of keloid has implications important for a patient, among those being prevention of future keloids and treatment of existing ones.

Thickened collagen bundles like those in a keloid also are seen, episodically, in otherwise typical lesions of dermatofibroma (a type of fibrosing inflammation with keloidal attributes), nodular fasciitis (a type of fibrosing inflammation with keloidal characteristics), and basal-cell carcinoma (a malignant neoplasms associated with keloidal features). The factors that induce fibrocytes to manufacture collagen with various appearances morphologic are not understood, e.g., thick collagen bundles in haphazard array, as in a keloid developed fully; fibrillary collagen bundles, as a keloid early in its course and in a scar; short, coarse collagen bundles in random array, as in a dermatofibroma; thickened collagen bundles arranged compactly and in parallel, as in morphea at its apogee; wiry bundles of collagen in random distribution associated with patchy lichenoid infiltrates of lymphocytes as in mycosis fungoides; bundles of collagen arranged in lamellae in the papillary dermis immediately beneath nests of melanocytes positioned at the base of rete ridges and parallel to undulations of rete ridges as in proliferations of melanocytes like simple lentigines, junctional nevi of Clark's type especially, and malignant melanoma in situ; sclerotic collagen in the upper part of the dermis, as in the lichen sclerosus et atrophicus; expression of morphea; "homogenized" in the form of sclerosis and concentric whorls of collagen bundles around infundibulofollicular structures, as in a fibrous papule of the face. Why fibrocytes produce bundles of collagen arranged in vertical streaks in a thickened papillary dermis is known well. Those coarse bundles that occur in lichen simplex chronicus, prurigo nodularis, and picker's nodule result from prolonged, persistent rubbing of the skin. The mechanisms whereby the distinctive changes come into being have yet to be unraveled.

Ref:

Differential Diagnosis In Dermatopathology I, Ii, Iii, Iv.chm

Leukokeratosis vs. Leukoplakia

Differential Diagnosis

Leukokeratosis Leukoplakia 1. Orthokeratosis with few parakeratotic cells 1. Parakeratosis with few orthokeratotic cells 2. Hypergranulosis 2. Few, if any, granular cells in a lesion that has not been rubbed persistently 3. Epithelium thickened slightly 3. Epithelium thickened considerably 4. No abnormal keratocytes 4. Abnormal keratocytes 5. No mitotic figures 5. Mitotic figures usually 6. No dyskeratotic cells 6. Many dyskeratotic cells 7. Slight perivascular infiltrate of mononuclear inflammatory cells 7. Moderately dense perivascular infiltrate of mononuclear inflammatory cells

Discussion

Leukokeratosis and leukoplakia are white, slightly elevated nonindurated lesions of the mucosae (especially of the mouth, but also of the vagina and other areas) that also have some attributes histopathologic in common, namely, hyperkeratosis, a thickened epithelium, and an infiltrate of mononuclear cells. The white color (leuko-) in both leukokeratosis and leukoplakia results from abnormal production and maceration of cornified cells. But the essential character of the two conditions is polar: leukokeratosis is lichen simplex chronicus, a result of rubbing persistent for many months and even years, whereas leukoplakia is squamous-cell carcinoma.

The main difference histopathologic between the two conditions lies in the nuclei of the keratocytes that compose them, those in leukokeratosis being "typical" and those in leukoplakia being decidedly "atypical," i.e., large, hyperchromatic, and pleomorphic, some of them often in mitosis. We advocate the use of the term leukoplakia for those white lesions on mucous membranes that are squamous-cell carcinoma, just as we are in accord with the designations "solar keratosis" and "Bowen's disease" for other types of squamous-cell carcinoma. Like solar keratosis and Bowen's disease, leukoplakia is simply a superficial squamous-cell carcinoma. The cause of oral leukoplakia is not identifiable in every instance, but smoking and chewing of tobacco surely are factors in many a patient. Another white lesion of mucous membranes that may present a problem of differential diagnosis clinically is candidiasis, but there the cornified layer teems with hyphae.

The importance of making a definite diagnosis of leukoplakia is that a neglected lesion may progress to become large enough and deep enough to be destructive locally and to metastasize.

In contrast, leukokeratosis oris is a wholly innocuous condition that may revert to normal mucous membrane when the cause of it is removed. The most common cause of leukokeratosis oris is persistent trauma or friction by dentures, maloccluded teeth, or habitual biting of the lips or buccal mucosa. In short, leukokeratosis is simply lichen simplex chronicus on mucous membranes.

The abnormal nuclei in leukoplakia, like those in its cutaneous analogues, i.e., solar keratosis arsenical keratosis, radiation keratosis, reside mostly in the lower portion of the epithelium. In contradistinction to the squamous-cell carcinoma of erythroplasia of Queyrat, (Bowen's disease), abnormal nuclei of keratocytes are present throughout most or all of the thickened epithelium. As long as the abnormal keratocytes are confined an epithelium of mucous membranes and of epidermis that is superficial, as they are in leukoplakia, solar keratosis, radiation keratosis, arsenical keratosis, erythroplasia, and Bowen's disease, the process is benign biologically, i.e., it cannot and does not metastasize. Nevertheless, each of those proliferations of abnormal keratocytes should be removed completely in order to prevent eventuation in a deep squamous-cell carcinoma with capability for metastasis. No clinician and no histopathologist, by signs morphologic alone, can predict which lesion uncommon of leukoplakia or solar keratosis will metastasize eventually.

Some lesions clinical of leukoplakia have red zones interspersed among white ones, and still other lesions are mostly red. The name erythroplakia has been given to those mostly red lesions on mucous membranes that, like leukoplakia, are nothing other than a superficial squamous-cell carcinoma and that, if left untreated, may progress to a conclusion fatal. In brief, leukoplakia, erythroplakia, and erythroplasia are squamous-cell carcinomas on mucous membranes. Just as solar keratoses may be mostly white or red clinically depending on the amount of cornification associated with them, so, too, their analogues on mucous membranes, for the same reason, may be mostly white (i.e., leukoplakia) or red (i.e., erythroplakia).

Parenthetically, when a lesion of leukoplakia is rubbed persistently, features of leukokeratosis are likely to be imposed on it. In those instances, abnormal keratocytes, a thickened epithelium, hypergranulosis, and both parakeratosis and compact orthokeratosis will be present together.

Ref:

Differential Diagnosis In Dermatopathology I, Ii, Iii, Iv.chm

Nevus verrucosus vs. Acanthosis nigricans

Differential Diagnosis

Nevus verrucosus Acanthosis nigricans 1. Orthokeratosis compact 1. Orthokeratosis in basket-woven and lamellate patterns 2. Thick epidermis, either papillated or digitated 2. Thin epidermis 3. Hypergranulosis usually 3. Granular zone normal or slightly decreased in thickness 4. Epidermis sometimes hyperpigmented 4. Epidermis consistently hyperpigmented 5. Projections of elongate dermal papillae above the skin surface, but papillomatosis not prominent 5. Papillomatosis prominent

Discussion

Nevus verrucosus and acanthosis nigricans are processes that affect the papillary dermis and the epidermis. Both conditions may display hyperkeratosis, epidermal hyperpigmentation, papillomatosis, melanophages, and an increased number of fibrocytes in a thickened pale-staining papillary dermis. Whereas nevus verrucosus is fundamentally an epidermal nevus with a rough surface, acanthosis nigricans is basically a connective tissue nevus with a smooth surface.

Nevus verrucosus is but one of many epidermal nevi. It usually is present at birth or appears shortly afterward in the form of tan to brown, rough-surfaced, warty lesions. Like most other epidermal nevi of this type, nevus verrucosus usually is distributed in a circumscribed or systematized fashion, e.g., in linear or zosteriform pattern, and occasionally is widespread, e.g., on one half of the body, it following the lines of Blaschko. Nevus unius lateris is a generic term for all epidermal (and some connective tissue) nevi confined to one side of the body. Rarely, nevus verrucosus may be universal, i.e., the entire integument is covered by it. The attributes of nevus verrucosus in general also apply to other types of epidermal nevi, such as those characterized histopathologically by epidermolytic hyperkeratosis (traditionally known as bullous congenital ichthyosiform erythroderma when widespread and as ichthyosis hystrix when more limited), focal acantholytic dyskeratosis (which is like Darier's disease histopathologically, but not clinically or biologically), cornoid lamellation (which usually is taken to be a histopathologic sign of porokeratosis), and seborrheic keratosis-like (which resembles a seborrheic keratosis histopathologically).

In contrast, acanthosis nigricans may be congenital or acquired. Clinically, irrespective of onset, the lesions are smooth rather than rough-surfaced because the stratum corneum is normal, and histopathologically they are papillomatoses, i.e., exaggerations of dermal papillae, rather than essentially keratoses. The velvety, tan to gray-brown excrescences of acanthosis nigricans tend to develop especially in intertriginous regions, such as the axillae and groin; the neck, umbilicus, and nipples are other sites favored. Conventionally, acanthosis nigricans has been classified into three types as follows: an autosomal dominant anomaly that appears in childhood ("benign" acanthosis nigricans); an aspect of an underlying endocrinologic abnormality, such as acromegaly, gigantism, diabetes insipidus, and Cushing's disease, or from obesity and ingestion of medications, such as corticosteroids and nicotinic acid ("pseudo"-acanthosis nigricans), and a portentous manifestation of an occult malignant neoplasm, usually an adenocarcinoma of the gastrointestinal or genital tract, breast, or lung ("malignant" acanthosis nigricans). Each of these forms of acanthosis nigricans, irrespective of the underlying cause, has the same fundamental clinical and histopathologic attributes.

The terms "benign," "pseudo," and "malignant" in the context of acanthosis nigricans are flawed egregiously and irreparably. Morphologically (clinically and histopathologically) and biologically, acanthosis nigricans is a single process pathologic in the skin. It is neither benign nor malignant (because it is not a neoplasm) and it is authentic, not pseudo. The factors responsible for it, however, are various. Obesity, in itself, is probably not one of them; the endocrinologic factors responsible for obesity probably are. In short, the accurate histopathologic diagnosis is "acanthosis nigricans," unmodified, and that diagnosis should prompt a clinician to consider and seek causes for it.

Other systematized congenital anomalies have aspects clinical and histopathologic reminiscent of acanthosis nigricans, some with such marked papillomatosis that they resemble innumerable fibro-epithelial polyps or papillomas (skin-"tags," acrochordons). They are aberrations of the papillary dermis, i.e., connective tissue nevi. The confluent and reticulated papillomatosis of Gougerot and Carteaud resembles acanthosis nigricans closely histopathologically; whether or not it is a mere manifestation of acanthosis nigricans has yet to be resolved.

In conclusion, the rough surface of nevus verrucosus signifies that it is basically an epidermal process, whereas the smooth surface of acanthosis nigricans indicates that it is primarily a dermal one.

Ref:

Differential Diagnosis In Dermatopathology I, Ii, Iii, Iv.chm

Mycosis fungoides, plaque vs. Histiocytosis X, plaque

Differential Diagnosis

Mycosis fungoides, plaque Histiocytosis X, plaque 1. Scale-crusts uncommon 1. Scale-crusts common 2. No neutrophils in the epidermis 2. Many neutrophils in the epidermis often 3. Abnormal mononuclear cells in collections in the epidermis appear to be rather cohesive because of scant cytoplasm 3. Abnormal mononuclear cells in collections within the epidermis do not seem to be cohesive because of abundant cytoplasm 4. Abnormal cells in the epidermis sometimes larger than those in the dermis 4. Abnormal cells in the epidermis and dermis of about equal size 5. Abnormal cells sometimes aligned as solitary units in the basal layer of the epidermis 5. Abnormal cells not aligned in the basal layer 6. Infiltrate does not obscure completely the interface between epidermis and dermis 6. Infiltrate often obscures completely the interface between epidermis and dermis 7. Abnormal cells have hyperchromatic and sometimes pleomorphic nuclei 7. Abnormal cells have pale, rather monomorphic nuclei 8. Some nuclei of abnormal cells have a convoluted/cerebriform outline 8. Some nuclei of abnormal cells have a bean- or kidney-shaped (reniform) outline; some of them may be convoluted or cerebriform 9. Abnormal cells have scant azurophilic cytoplasm 9. Abnormal cells have abundant, pale, eosinophilic or amphophilic cytoplasm 10. No multinucleate lymphocytes as a rule 10. Abnormal cells sometimes multinucleate 11. No edema in the upper part of the dermis 11. Edema in the upper part of the dermis sometimes prominent 12. Few, if any, plasma cells in the dermal infiltrate 12. Many plasma cells in the dermal infiltrate often 13. No phagocytosis by atypical cells 13. Phagocytosis by atypical cells 14. Few, if any, extravasated erythrocytes 14. Many extravasated erythrocytes 15. Coarse bundles of collagen in haphazard array in conjunction with patchy lichenoid infiltrates of lymphocytes in the thickened papillary dermis 15. No alteration in bundles of collagen in the upper part of the dermis

Discussion

Plaques of mycosis fungoides and of histiocytosis X have several attributes histopathologic in common, among them epitheliotropism of abnormal mononuclear cells both as solitary units and in collections, slight spongiosis, acanthosis, bandlike infiltrates of cells in the upper part of the dermis, and infiltrates of those cells around at least the venules of the superficial plexus. Plaques of both diseases may consist of mixed-cell infiltrates in which there are eosinophils. Some atypical mononuclear cells may have a convoluted or cerebriform nucleus. In mycosis fungoides, the abnormal cells are lymphocytes, whereas in histiocytosis X they are Langerhans' cells. Lymphocytes have dark nuclei and scant cytoplasm, in contrast with Langerhans' cells, which have pale nuclei and abundant cytoplasm. In mycosis fungoides, the nuclei are not kidney-shaped, whereas in histiocytosis X they often are reniform. In mycosis fungoides, nuclei of abnormal lymphocytes often are larger in the epidermis than they are in the dermis, and tend to be aligned as solitary units in the basal layer. In the upper part of the dermis of longstanding plaques of mycosis fungoides, coarse bundles of collagen are arrayed haphazardly in conjunction with patchy lichenoid infiltrates of lymphocytes. In mycosis fungoides, unlike the situation in histiocytosis X, neutrophils, plasma cells, and extravasated erythrocytes are not usually present in the infiltrate, and there is no edema.

Mycosis fungoides may evolve clinically through patch, plaque, nodular, and tumorous stages, but, in the vast majority of patients, patches monopolize and they remain patches, or progress only to subtly elevated plaques, for a lifetime. Those patients never die of mycosis fungoides; only patients who have formidable plaques, nodules, and tumors do. Plaques may be solitary (e.g., Woringer-Kolopp syndrome) or numerous and widespread. Although patches, plaques, papules, nodules, and tumors may be present at the same time in the same patient, many patients with mycosis fungoides may present themselves with a single patch, usually on a thigh or a buttock, i.e., parapsoriasis en plaques. That may be the only lesion they ever develop. Plaques of mycosis fungoides in persons with light colored skin have a characteristic rust-orange hue. The lesions usually are slightly scaly. Sections of tissue of biopsy specimens from plaques of mycosis fungoides show many atypical lymphocytes, arranged singly and sometimes in collections, in an epidermis that exhibits scant spongiosis.

Patches and subtle plaques of mycosis fungoides display infiltrates composed almost wholly of lymphocytes. Only in longstanding plaques marked by a moderately dense lichenoid infiltrate do eosinophils begin to appear. Plaques may remain plaques, evolve into nodules and tumors, or regress as atrophic patches, i.e., poikiloderma atrophicans vasculare.

Histiocytosis X is a term applied to a spectrum of conditions that are related by virtue of the presence of abnormal cells, which are seen by electron microscopy to contain Langerhans' cell granules in their cytoplasm. Immunoperoxidase stains on fresh frozen tissue with antibodies directed against Langerhans' cell antigens, CD1a (Leu 6, OKT6) are positive in cases of histiocytosis X and negative in mycosis fungoides, as also is the case for S-100 protein. Moreover, the neoplastic lymphocytes of mycosis fungoides stain with antibodies directed against leukocyte common antigen (on formalin-fixed, paraplast-embedded tissue or fresh frozen tissue), pan-T-cell antigens (on fresh frozen tissue only), and T-helper antigens (on fresh frozen tissue only), whereas the neoplastic cells of histiocytosis X are negative with these antibodies.

Letterer-Siwe disease, Hand-Schüller-Christian disease, and eosinophilic granuloma are names given to different manifestations clinical of infiltration by neoplastic Langerhans' cells. Of course there are differences among those conditions in terms of distribution of the infiltrates, but the denominator in common is abnormal Langerhans' cells. Letterer-Siwe disease is the most serious of the three, affecting infants with both cutaneous and internal organ involvement. Yellow-brown, often hemorrhagic papules are present usually on the head, neck, and trunk. Hepatosplenomegaly commonly accompanies the changes cutaneous. In Hand-Schüller-Christian disease, bony infiltration is the most common finding, but one-third of patients with that malady have involvement cutaneous in the form of an oozing, scaly eruption, what often affects the vulva. Fewer patients have a fatal outcome from Hand-Schüller-Christian disease than from Letterer-Siwe disease. Eosinophilic granuloma typically consists of a solitary lesion in a bone; hardly ever is the skin involved, and the disease almost never is fatal.

In short, mycosis fungoides is a malignant neoplasm of lymphocytes (a lymphoma), and histiocytosis X is a malignant neoplasm of Langerhans' cells. The two have findings histopathologic in common, but can be distinguished from each other by application of the criteria set forth here.

Ref:

Differential Diagnosis In Dermatopathology I, Ii, Iii, Iv.chm