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SPOT THE DIAGNOSIS |
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| Year : 2013 | Volume
: 58
| Issue : 4 | Page : 290-293 |
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| Psoriasiform dermatoses: Microscopic approach |
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Rajalakshmi Tirumalae
Department of Pathology, St. John's Medical College, Bangalore, Karnataka, India
| Date of Web Publication | 25-Jun-2013 |
Correspondence Address:
Rajalakshmi Tirumalae
Associate Professor, Department of Pathology, St. John's Medical College, Bangalore - 560 034, Karnataka
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/0019-5154.113945
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 Abstract | | |
Psoriasiform dermatoses often pose challenges to both dermatologists and pathologists alike. With proper clinicopathologic correlation and a systematic approach, it is possible to arrive at a specific diagnosis in most cases. This article attempts to outline a practical, step-wise method of looking at these cases and highlights some important clues in individual conditions.
Keywords: Histopathology, psoriasiform dermatoses, psoriasis
How to cite this article:
Tirumalae R. Psoriasiform dermatoses: Microscopic approach. Indian J Dermatol 2013;58:290-3 |
What was known?
1. Psoriasiform dermatoses comprise of a wide variety of diseases that resemble each other both at clinical and histologic levels.
2. Correct diagnosis is reached with good clinico.pathologic correlation
2. Stratum corneum holds a lot of subtle, but important clues, which should
be elicited carefully.
| Introduction | |  |
Psoriasiform dermatoses (PD) encompass a wide array of diseases, some of which show both clinical and histologic overlap. It is an intimidating task even to experienced microscopists to give a precise diagnosis every time and one relies heavily on clinical correlation. However, it is possible to assign specific diagnoses in most cases with a logical, systematic approach. Many textbooks give detailed descriptions about individual diseases and this review does not attempt to replicate them. [1],[2] This article outlines the microscopic approach and emphasizes certain important principles and clues that should always be at the back of one's mind when evaluating these cases.
Psoriasis literally mean "itchy condition," derived from Greek. [3] Psoriasiform pattern is defined histologically by the finding of elongated rete ridges of roughly equal length, which alternate with long dermal papillae. According to Ackerman et al., psoriasiform pattern forms a major subset of perivascular dermatitis, the largest group of inflammatory skin diseases. [3] Perivascular dermatitis can be associated with epidermal changes such as psoriasiform, interface/lichenoid, ballooning or spongiotic patterns. Often, these changes are found in combination and the components of this mixture give important clues to the correct diagnosis. PD can be broadly classified as:
- Psoriasiform only: Even or uneven psoriasiform
- Combinations: Psoriasiform lichenoid, Spongiotic psoriasiform, Spongiotic psoriasiform lichenoid
These can be further deciphered based on the dominant inflammatory cell infiltrate i.e., lymphocytes only or admixture with other cells such as eosinophils, histiocytes or plasma cells. These, coupled with a detailed, stepwise analysis of findings beginning right from the top of the stratum corneum, help one arrive at the right diagnosis.
| Scanning Magnification | | |
Examination of microscopic sections under scanning (×2 or ×4) magnification forms the first step, which is under-rated. The presence of evenly elongated, thin rete ridges with equally long dermal papillae can imply only one condition i.e., psoriasis. All other diseases exhibit an uneven psoriasiform pattern, i.e., rete ridges are of uneven lengths and thickness with thick supra-papillary plates. One should also observe at this juncture, the depth (superficial or both superficial and deep) and pattern of the dermal infiltrate i.e., perivascular, lichenoid or nodular.
| Changes in Stratum Corneum | | |
Stratum corneum often holds the most important but often subtle features that aid diagnosis. It mirrors the temporal evolution of a disease. The normal basket-weave pattern is lost in most PD and it is common to find parakeratosis. Parakeratosis refers to the presence of nuclei within the cornified layer and is the consequence of a rapid turnover of the epidermal keratinocytes, instead of the usual 4 weeks. [3] The presence of a normal basket-weave pattern above this indicates a recent onset.
Parakeratosis can be present in small mounds or may be broad and confluent. [3] Often, it is associated with collections of neutrophils and/or plasma, called "scale crust." Mounds of parakeratosis can be present throughout the epidermis in conditions like psoriasis and dermatophytosis, confined to the infundibular ostia (Seborrheic dermatitis) or seen in both locations, like in pityriasis rubra pilaris (PRP). [1],[2],[3] The classic "checkerboard" pattern of PRP i.e., parakeratosis staggered in both vertical and horizontal fronts is often difficult to find, even on multiple sections [Figure 1]a. [1] Confluent parakeratosis is seen in dermatophytosis, syphilis, pityriasis lichenoides chronica and most importantly, in mycosis fungoides (MF). Sharply defined, thick zones of parakeratosis alternating with orthokeratosis and mild papillomatosis is a feature of inflammatory linear epidermal nevus (ILVEN). [3] Crowding and atypia of parakeratotic nuclei is seen in Bowen's disease. [4] | Figure 1: (a) Checkerboard pattern of parakeratosis in PRP (H and E, ×200) (b) Parakeratosis in tiers in eruptive psoriasis (H and E ×100) (c) Marked pallor of keratinocytes in the upper layer in acrodermatitis enteropathica (H and E, ×200) (d) Hairy palm sign in LSC (H and E, ×40)
Click here to view |
When parakeratosis with neutrophils is seen beneath a basket-weave cornified layer, one has to look carefully for the presence of fungal hyphae. One must remember that large amounts of plasma and a rapidly proliferating epidermis are hostile to fungi, which prefer the comfort of the niche just below the orthokeratotic zone, constituting the "sandwich" sign. [5] It is useful to lower the condenser of the microscope when attempting this, as the hyphae are better seen. Parakeratosis with neutrophils is seen alternating with zones of orthokeratosis vertically, reflecting the periodicity of eruptive/guttate psoriasis [Figure 1]b. Significant amounts of plasma in the scale crust go against a diagnosis of psoriasis, except on volar skin. Debris and fragments of mites are frequently seen in Norwegian scabies. [1]
Stratum corneum is completely absent in diseases with a markedly accelerated epidermal turnover, clinically presenting as erythroderma. This is commonly seen in psoriasis, MF, and sometimes, in PRP. [1],[3]
| Changes in the Rest of Epidermis | | |
Diminished or absent granular layer is seen in classic psoriasis. But, classic psoriasis is rarely biopsied. What one sees under the microscope are clinically atypical or treated, unresponsive lesions. In such instances, the granular layer may be normal or thickened, as in other diseases like pityriasis rosea (PR), lichen simplex chronicus or allergic contact/nummular dermatitis. [1],[6] Too much stress should not be placed on this feature.
Pallor of keratinocytes in the upper epidermal layers is seen in psoriasis, PR and most importantly, in certain nutritional deficiency diseases [Figure 1]c. [1],[3],[7] In psoriasis, pallor is mediated by neutrophils that migrate through the epidermis into the stratum corneum. [3] Presence of neutrophils in between keratinocytes with early spongiosis indicates either psoriasis or dermatophytosis. In diseases like pellagra, acrodermatitis enteropathica and glucagonoma syndrome, the keratinocytes appear extremely pale due to accumulation of glycogen.
Although psoriasis is primarily spongiotic, it never eventuates in the formation of spongiotic vesicles. The finding of spongiotic vesicles in a PD are seen in allergic contact/nummular dermatitis and seborrheic dermatitis. These begin as purely spongiotic diseases in the early phase and psoriasiform hyperplasia develops in the subacute and chronic phases. In seborrheic dermatitis, the finding of scale crusts at the dilated infundibular openings accompanied by spongiosis points to the diagnosis. [1],[3] Spongiotic psoriasiform pattern is also encountered in patch-stage MF. [3] [Table 1] summarizes some of the important differentiating microscopic features in common PD. | Table 1: Histopathologic features useful in differentiating common psoriasiform dermatoses
Click here to view |
| Changes in the Papillary Dermis | | |
Psoriasis is characterized by thinning of supra-papillary plates and elongated dermal papillae that contain dilated, tortuous capillaries. This is in keeping with the "squirting papilla" concept that explains its pathogenesis. [8] The presence of extravasated erythrocytes is a sign of acuteness and is seen in eruptive psoriasis and PR. [3]
Vertical streaks of collagen with uneven psoriasiform acanthosis and compact orthokeratosis is diagnostic of lichen simplex chronicus (LSC). [1],[3] In fact, the biopsy resembles volar skin on scanning magnification, except for the presence of pilosebaceous structures, giving rise to the "hairy palm" sign [Figure 1]d. [9] Changes of LSC can be superimposed on any chronic, itchy dermatitis including psoriasis. In contrast, thin haphazard, wiry bundles of collagen are seen in the papillary dermis in PLC and MF. This finding reflects the chronicity of the infiltrate and one should look carefully for other features of early MF.
| Nature of the Infiltrate | | |
Most PD are dominated by lymphocytes in the dermis. When one meets eosinophils among them, it indicates allergic/contact dermatitis or a drug eruption. However, eosinophils are not a pre-requisite for diagnosis of either of these conditions. [1],[3] Histiocytes and plasma cells in a PD with scale crusts should ring a bell for secondary syphilis. [1],[3] It is also common to find some ill-formed granulomas in such instances and special stains for spirochaetes must be employed. However, plasma cells are absent in early lesions. [3]
Superficial and deep infiltrates are seen in syphilis and lichen striatus (LS). [3] In LS, there is a psoriasiform lichenoid pattern with deep infiltrates of lymphocytes along the adnexae, specially so around the eccrine glands.
| Psoriasis-Variants and Caveats | | |
Classic psoriasis is rarely biopsied, as stated earlier. Problems arise in interpretation of treated lesions. In a study of treated psoriasis by Boer, et al., dilated, tortuous capillaries emerged as the most reliable sign of psoriasis in all its stages and forms. [6] This is retained even when the granular layer and supra-papillary plates have returned to normal. On the scalp, psoriasis is accompanied by papillomatosis, atrophy of sebaceous glands and necrotic keratinocytes in the epidermis, features helpful in distinction from seborrheic dermatitis. [10]
Psoriasis on volar skin shows large amounts of plasma in the scale crust and is difficult to tell apart from allergic contact/dyshidrotic dermatitis. In such an instance, one should look for the tortuous dermal capillaries and presence of neutrophils in the epidermis. Neutrophils are not seen in allergic contact dermatitis, unless the lesions are secondarily infected due to excoriation. [3] But, in practice, it is not very easy to render a specific diagnosis every time. One must recall that finding significant numbers of eosinophils is not a feature of psoriasis and is absent, even when it is triggered by a drug. [11] Pustular psoriasis is also a teaser, especially when occurring de novo and classic changes may not be found. Finding neutrophils amidst the keratinocytes at the periphery of the pustule is helpful, together with tortuous dermal vessels. [12]
In patients with a predisposition to psoriasis, its histologic changes are seen even with other dermatologic conditions, the most important being with MF. It is important to recognize both the conditions. This process is a result of Koebnerization. [3]
| Histologically Indistinguishable Diseases | | |
There are some diseases that appear identical under the microscope, but can be told apart clinically. The most important group includes allergic contact dermatitis, nummular dermatitis, id reaction, dyshidrotic dermatitis (pompholyx) and photoallergic dermatitis. [3] Allergic contact dermatitis corresponds to the site of its trigger. Nummular dermatitis appears as discoid/coin-shaped lesions. Pompholyx occurs on acral skin, at the side of the digits while photoallergy is seen in sun-exposed sites like the V of the neck. "Actinic reticuloid" histologically is photoallergic dermatitis with superimposed LSC-like changes.
PR and erythema annulare centrifugum are histologic twins and one has to go back to the clinical presentation. [3]
| Neoplasms with Psoriasiform Pattern | | |
The most important condition in this category is MF. Virtually every combination of patterns, i.e., psoriasiform, spongiotic psoriasiform, psoriasiform lichenoid and spongiotic psoriasiform lichenoid is seen in MF. [3] Mild to moderate amounts of spongiosis is seen, but never to the extent ending in vesiculation. The most important feature is the presence of lymphocytes in the epidermis disproportionate to the amount of spongiosis. These are disposed in a linear fashion along the basal layer and may also be present in a pagetoid fashion, reaching almost up to the granular layer. [13] Other signs like dermal papillae stuffed with lymphocytes, wiry collagen, absence of dermal edema also help. [12] It cannot be overemphasized that this diagnosis should be made in the right clinical context and never on a single biopsy specimen. If there are features suspicious for MF, it is prudent to request repeat biopsies from multiple, preferably non-sun exposed sites for a specific diagnosis. Ancillary tests like immunostains and T-cell gene rearrangements are often futile in early lesions.
Psoriasiform hyperplasia can occur over a dermatofibroma [Figure 2]a. [3] Bowen's disease also shows psoriasiform acanthosis and is generally not difficult to pick up as the keratinocyte atypia is striking. Clear cell acanthoma is a rare tumor with a psoriasiform appearance [Figure 2]b. There are broad, uneven rete ridges with marked pallor of the keratinocytes throughout the epidermal thickness. [14] One may also find some neutrophils and nuclear debris in the spinous layer. | Figure 2: (a) Psoriasiform hyperplasia overlying a dermatofibroma (H and E, ×40) (b) Clear cell acanthoma showing broad, fused rete ridges and pallor throughout the epidermis (H&E, ×100 Image courtesy: Dr. Almut Boer)
Click here to view |
| Key Points | | |
- Use a step-wise, logical approach.
- Start with scanning magnification: Uneven vs. even psoriasiform, purely psoriasiform or combination of epidermal patterns.
- Spend time in examining the stratum corneum, especially to elicit subtle changes.
- Observe changes in the rest of the epidermis, particularly the follicular infundibula.
- Determine the nature of the inflammatory cell infiltrate and its depth.
- Pay attention to the changes in dermal vasculature.
- Don't forget that MF and drugs can mimic any of these patterns.
- Be aware of the temporal evolution of lesions, their pitfalls and simulators.
- Never sign out a PD without employing fungal stains.
- Look at the clinical findings AFTER you have made a preliminary impression and note the site of the biopsy, this is the simplest tool for clinico-pathologic correlation.
- If one is unable to arrive at a specific diagnosis despite all this, give descriptive reports using language understood by the dermatologist. This should include the epidermal pattern and nature of the infiltrate, at least.
- Remember that the terms acute, subacute and chronic are clinical and their use in histopathology reports do not reflect specificity. For example, psoriasiform spongiotic pattern with lymphocytes is far better than saying "chronic dermatitis." To the clinician, who has access to the complete history and clinical findings, this implies allergic/contact dermatitis and he will proceed accordingly.
- When in doubt, ask. Incomplete requisition forms are a major problem faced by pathologists world over and it is important to pick up the phone and obtain that missing piece of information that will solve the puzzle.
| Conclusion | | |
The features described above are neither complete nor exhaustive. The approach outlined here is simple, practical and repeatable. It cannot be emphasized too much that the bottom-line of a good histopathology report is clinico-pathologic correlation and the pathologist should take the onus of signing out meaningful reports.
| References | | |
| 1. | Weedon D. The psoriasiform reaction pattern. In: Weedon D, editor. Skin pathology. 3 rd ed. London: Churchill Livingstone; 2009. p. 75-81. 
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| 2. | Mobini N, Toussaint S, Kamino H. Noninfectious erythematous, papular and squamous diseases. In: Elder DE, Johnson BL, Elenitsas R, editors. Lever's histopathology of the skin. 4 th ed. Philadelphia, PA: Lippincott Williams and Wilkins; 2005. p. 183-91.
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| 3. | Ackerman AB, Boer A, Bennin B, Gottlieb G. Histologic diagnosis of inflammatory skin diseases. An algorithmic method based on pattern analysis. 3 rd ed. New York: Ardor Scribendi; 2005.
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| 4. | Khopkar U, Ackerman AB. Diagnosis from the stratum corneum alone. Dermatopathology Practicla and conceptual 1996;2:2.
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| 5. | Ackerman AB. Clue 24 in Clues to diagnosis in dermatopathology. 2 nd ed. New York: Ardor Scribendi; 2001.
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| 6. | Werner B, Böer A. Treated Psoriasis: Clues to a difficult diagnosis. Dermatopathology Practical and conceptual 2006;12:3.
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| 7. | Gonzalez JR, Botet MV, Sanchez JL. The histopathology of acrodermatitis enteropathica. Am J Dermatopathol 1982;4:303-11.
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| 8. | Pinkus H, Mehregan AH. On the evolution, maturation and regression of lesions of psoriasis. Am J Dermatopathol 1980;2:287-8.
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| 9. | Ackerman AB. Clue 27 in Clues to diagnosis in dermatopathology. 2 nd ed. New York: Ardor Scribendi; 2001.
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| 10. | Werner B, Brenner FM, Boer A. Histopathologic study of scalp psoriasis: Peculiar features including sebaceous gland atrophy. Am J Dermatopathol 2008;30:93-100.
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| 11. | Laga AC, Vleugels RA, Qureshi AA, Velazquez EF. Histopathologic spectrum of psoriasiform skin reactions associated with tumor necrosis factor-a inhibitortherapy. A study of 16 biopsies. Am J Dermatopathol 2010;32:568-73.
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| 12. | Ackerman AB. Clue 39 in Clues to diagnosis in dermatopathology. 2 nd ed. New York: Ardor Scribendi; 2001.
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| 13. | Inchara YK, Rajalakshmi T. Early Mycosis Fungoides vs. Inflammatory mimics: How reliable is histology? Indian J Dermatol Venereol Leprol 2008;74:462-6.
[PUBMED]  |
| 14. | Kerl H. Clear-cell acanthoma Hautarzt 1977;28:456-62.
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What is new?
1. A stepwise, systematic histopathologic approach enables one to arrive at
a specific diagnosis in most cases of PD.
2. Stratum corneum holds a lot of subtle, but important clues, which should
be elicited carefully.
[Figure 1], [Figure 2]
[Table 1] |
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