Interface dermatitis (Dermatopathology)

Interface dermatitis

1. Interface dermatitis Dr.Shanmathi Sethumadhavan , 2 nd year PG, Dept of DVL , TVMCH Moderator: Dr. P.Sivayadevi, Associate Professor Indian Journal of Dermatology, Venereology, and Leprology | May-June 2013 | Vol 79 | Issue 3

2. I n t r od u ction Primary pathology involves the " interface“ – DEJ Components of the interface- single anatamico – physiological unit Basal layer of epidermis Dermoepidermal junction Adventitial dermis – papillary + periadnexal dermis Cell mediated immunologic reactions whose targets are basal keratinocytes that reside above the dermoepidermal junction

3. Pattern of inflammation in which lymphocytes aggregate around the dermal-epidermal junction  obscuring the junction at scanning magnification . Vacuolar change , necrotic keratinocytes , spongiosis T-cell-mediated cytokine damage is most likely mechanism cytotoxic damage, or apoptosis of keratinocytes become detached from their neighbors, become round, undergo a sequence of events, degradation of nuclear DNA, lysis of nuclei coagulation of proteins in cytoplasm, without spilling enzymes Termed as dyskeratotic cells, When they find their way into papillary dermis, termed as colloid, cytoid or Civatte bodies

4. Morphological changes Primary changes Basal cell vacuolization ( Vacuolar alteration ): Most prominent feature Expansion of cytoplasm  Partial or complete destruction of basal cells  produces tiny vacuoles along DEJ Total absence of basal cell with spinous keratinocytes abutting papillary dermis  squamatization of basal layer -polygonal shape and pink cytoplasm Confluent basal cell damage  clefts and subepidermal vesicles . Vacuolar changes of basal cells with sparse perivascular lymphocytic infiltrate. Morbilliform drug eruption (H and E, ×100)

5. B) Apoptotic keratinocytes (C olloid or Civatte bodies ) : Syn : Individually necrotic keratinocytes Dyskertotic keratinocytes Seen as small, rounded, eosinophilic , hyaline, anucleate structure , Are slightly smaller than basal keratinocyte . May be seen in basal layer, in upper papillary dermis, individually or in clumps, or in mid- and upper spinous layers Figure 2: Colloid ( Civatte ) bodies at the dermo ‐epidermal junction with basal cell vacuolization with melanophages in the upper papillary dermis. Lupus erythematosus (H and E, ×400)

6. C) Obscuring of dermo- epidermal junction by inflammatory cells : Lymphocytes are M / C Eosinophils, neutrophils , mast cells , and histiocytes may be seen. Obliterates clear distinction between epidermis and papillary dermis Density of inflammatory infiltrate is variable Figure 3: Several lymphocytes in the basal cell layer obscuring the DEJ with basal cell vacuolization and few apoptotic keratinocytes in the lower spinous zone. Erythema multiforme (H and E, ×400)

7. 2. Secondary changes Epidermal changes: Depend on disease time of biopsy in course of evolution or devolution of disease site of biopsy Acanthosis, hypergranulosis -LP Thick compact orthokeratotic stratum corneum - LP Thin and atrophic epidermis – LE , atrophic LP Irregular epidermal hyperplasia - verrucous DLE

8. Papillary dermal changes Secondary to basal cell damage Papillary dermis undergoes expansion to accommodate inflammatory infiltrate Fibrosis or sclerosis M elanin Incontinence into papillary dermis Melanophages Other changes Mucin deposits in reticular dermis -LE Perivascular and periadnexal infiltrates of lymphocytes in mid- and deep reticular dermis lymphocytic lobular panniculitis – lupus profundus Sclerosis of thickened papillary dermis with smudging of dermo-epidermal junction. B luish -grey mucin in upper reticular dermis. LE (100X) Thickened papillary dermis with sparse lymphocytic infiltrate and numerous melanophages. persisting basal cell vacuolization. Lichen planus pigmentosus (100X)

9. Classification of Interface Dermatitis Prominent infiltrate in papillary dermis aligned in lichenoid pattern ( Lichenoid-interface dermatitis ): Dense band-like infiltrate in papillary dermis -Polycellular infiltrate Basal cell vacuolization may be inconspicuous or absent. Histologically, classified as: Prominent basal cell vacuolization ( Vacuolar-interface dermatitis ) : Basal cell vacuolization is most prominent Variable perivascular and interstitial infiltrates of lymphocytes . Paucicellular infiltrate

10. Parenthetically, a true lichenoid infiltrate is restricted to the papillary dermis seen typically in interface dermatitis, B and ‐like infiltrate often extends into the reticular dermis without any interface changes G ranulomatous conditions T uberculosis verrucosa cutis (TBVC ) L upus vulgaris B enign , premalignant, and malignant conditions L ichenoid keratosis Paget’s disease (both mammary and extramammary ) Bowen’s disease Resolving malignant melanoma

11. 3 . Le Boit’s classification depending on epidermal changes a) Acute cytotoxic type B asal cell vacuolization with L ymphocytes infiltrating lower epidermis Scattered necrotic keratinocytes at various levels in epidermis. Entire process is rapid  Does not interfere with epidermal keratinization Horny layer is unaffected -- maintains its normal basket weave arrangement. EM is prototype. Few necrotic keratinocytes Early EM M orbilliform drug Morbilliform viral eruptions Eruption of lymphocyte recovery Acute GVHD* Numerous necrotic keratinocytes Fully developed EM Acute LE TEN Radiation & chemotherapy -induced skin damage FDE ( eosinophils , neutrophils, & melanophages ) Pityriasis lichenoides et varioliformis ( parakeratosis ).

12. Numerous necrotic keratinocytes scattered in lower spinous zone with lymphocytes obscuring dermo-epidermal junction. Note normal basket weave stratum corneum. EM

13. E M . There is obscuration of the dermoepidermal junction with vacuolar alteration of the basal keratinocytes (A and B). Necrotic keratinocytes may be individual or confluent (B). The process may progress to frank subepidermal vesiculation (C). Toxic epidermal necrosis with confluent, fullthickness epidermal necrosis (D). P reservation of the basket-weave horn. Density of dermal inflammatory infiltrate is inversely proportionate to epidermal damage . Fairly dense in EM, Very sparse or even absent in TEN . Eosinophils are not seen as a rule

14. Erythema multiforme acute nature  orthokeratotic stratum corneum The earliest changes include vacuolization of the basal cell layer, tagging of lymphocytes along the dermoepidermal junction, and a sparse, superficial, perivascular lymphoid infiltrate. Mild spongiosis , papillary edema and RBC extravasation are seen. Necrosis of individual keratinocytes occurs in the basal unit is the hallmark of erythema multiforme . Later – lichenoid lymphohistiocytic infiltrate +/- eosinophils Satellite -cell necrosis- intraepidermal lymphocytes in close association with apoptotic keratinocytes, is frequently present.

15. Drug-induced EM more widespread keratinocyte necrosis, microscopic blister formation , and more pigmentary incontinence Herpes simplex associated erythema multiforme more spongiosis , exocytosis, liquefaction degeneration of the basal layer, and papillary dermal edema. Nuclear dust may be identified in the papillary dermis

16. SJS and TEN in bullous lesions, and in the central portion of target lesions , more epidermal necrosis -Full -thickness - numerous necrotic keratinocytes A subepidermal bulla. Sparse dermal inflammatory infiltrate and exocytosis Extravasated erythrocytes within the blister cavity . Melanophages within the papillary dermis -late lesions Eccrine epithelium – basal cell apoptosis to duct necrosis

17. Fixed drug eruption. There is obscuration of the dermoepidermal junction with a mixed inflammatory cell infiltrate composed of lymphocytes numerous eosinophils and neutrophils (A and B). Necrotic keratinocytes can be identified throughout all levels of the epidermis (A)and may tend toward confluence. A mixed perivascular infiltrate can be present in the deep dermis (C).

18. Acute GVHD typically occurs between 7 and 21 days after transplantation but may be seen as late as 3 months; classic triad skin lesions, hepatic dysfunction, and diarrhea . C hronic GVHD generally arises after a mean of 4 months, but may occur as soon as 40 days post transplantation usually generalized, rarely localized early lichenoid stage – cutaneous and oral lesions clinically similar to LP the skin may show extensive erythema and irregular hyperpigmentation late sclerodermoid stage Each stage can occur without the other. A poikiloderma may precede the eventual sclerodermoid stage GVHD

19. Graft versus host disease, acute. Lymphocytes tagging at the dermoepidermal junction and eliciting satellite -cell necrosis ( pathognomic )

20. Spongiosis Satellite cell necrosis

21. Acute graft versus host reaction (GvHR). There is a sparse lymphocytic infiltrate obscuring the dermoepidermal junction (A). Lymphocytes are present in the epidermis (exocytosis) with adjacent 2 or more individually necrotic keratinocytes in spinous layer ( satellite cell necrosis) ( B ). Chronic GvHR. There is acanthosis of the epidermis with hypergranulosis and a patchy band-like lymphocytic infiltrate. The dermis is fibrotic (C).

22. Grade 3 graft versus host reaction, subepithelial separation has resulted from confluent vacuolar change. Endothelial cell swelling and narrowing of endothelial lumen

23. b) Premature terminal differentiatio n Refers to an early development of a thick granular layer and compact stratum corneum A/w dense lichenoid infiltrates of lymphocytes. LP is prototype Mixed infiltrates: Lichenoid drug reaction(eosinophils) K eratosis lichenoides chronica (plasma cells) Few lymphocytes: Dermatomyositis L ichenoid GVHD Dense lymphocytic infiltrates: LP L ichenoid keratosis Lichenoid drug reaction especially Photolichenoid Acute GVHD DLE Lichen striatus

24. c) Irregular epidermal hyperplasia variant of permature terminal differentiation Show marked irregular epidermal hyperplasia Seen in H ypertrophic LP V errucous DL E S ome long- standing lichenoid drug eruptions

25. d) Interface dermatitis with psoriasiform hyperplasia Show interface changes as a secondary pathological feature Not classified as primary interface dermatitis. Lymphocytes and siderophages: Lichenoid variant of pigmented purpur ic dermatoses Eosinophils predominant: Urticarial pemphigoi d S ome drug eruptions Lymphocytes mostly: Mycosis fungoides L ichen striatus (True interface dermatitis ) Fully developed lesions of P ityriasis lichenoides (True interface dermatitis ) L ichen sclerosus C enter of porokeratosis Plasma cells : Secondary syphilis E arly acrodermatitis chronica atrophicans

26. e) Interface dermatitis with epidermal atrophy Represents late atrophic phase of several dermatoses Plasma cells: Late stage of acrodermatitis chronica atrophicans. Band of melanophages : Regressing malignant melanoma L ate pigmented patches of FDE. Lymphocytic infiltrate: Atrophic LP L ong -standing lesions of LE, d ermatomyositis P oikiloderma L ichen sclerosus et atrophicus C enter of old lesions of porokeratosis

27. Lichen planus

28. Lichen planus. There is compact orthokeratosis with no parakeratosis, wedgeshaped hypergranulosis, jagged acanthosis of the epidermis, and a band-like lymphocytic infiltrate obscures the dermoepidermal junction (A–C) . Necrotic keratinocytes are in the lower one-third of the epidermis with colloid bodies in the superficial papillary dermis (D)

29. Max Joseph Space/ Caspini Joseph space artifactual separation between the epidermis and the lichenoid infiltrate in dermis Lichen planus . Closer view shows lymphocytes and melanophages in the papillary dermis, vacuolar alteration of the basal layer, necrotic keratinocytes ( Civatte bodies), and enlarged keratinocytes with eosinophilic cytoplasm

30. Lichen planus Thick compact orthokeratosis Focal wedge-shaped hypergranulosis - tips of orifices of acrosyringia and base of follicular infundibula Broad irregular jagged acanthosis Dome-shaped dermal papillae Pointed or saw- toothed rete ridges – angulated hyperplasia Basal cell -vacuolar degeneration and Squamatisation(pale glassy cytoplasm ) B and-like dermal lymphocytic infiltrate -composed almost entirely of lymphocytes intermingled with macrophages. Pigment incontinence – melanophages in upper dermis , near base of lichenoid infiltrate Apoptotic , dyskeratotic ,colloid, hyaline, cytoid , or Civatte bodies 20 micron diameter Necrotic keratinocytes in lower epidermis and upper papillary dermis H omogenous round eosinophilic PAS positive , Diastase resistant

31. Colloid bodies Apoptotic , dyskeratotic ,colloid, hyaline, cytoid , or Civatte bodies 20 micron diameter Necrotic keratinocytes in lower epidermis and upper papillary dermis Homogenous round eosinophilic PAS positive , Diastase resistant Also seen in GVHD Lichen nitidus LE Drug reactions Inflammed keratoses Lichenoid acitinic keratoses Lichen planus like keratoses – focal parakeratosis and adjacent solar lentigenes Normal epidermis

32. Wickham's striae - focal increase in the thickness of the granular layer and of the total epidermis. Max-Joseph spaces- Occasionally, small areas of artifactual separation between the epidermis and the lichenoid infiltrate in dermis In some instances, the separation occurs in vivo and subepidermal blisters form - vesicular LP -due to extensive damage to the basal cells . DIF : Necrotic keratinocytes - stain in about 87% of the cases mainly for IgM but often also for IgG , IgA, C3, and fibrin. ” In old lesions the cellular infiltrate decreases in density, but the number of macrophages increases. In areas in which a basal cell layer has reformed, the dermal infiltrate no longer lies in close approximation to the epidermis. Chronic lesions may show considerable acanthosis , papillomatosis , and hyperkeratosis (hypertrophic LP).

33. Oral LP Parakeratosis Absent granular layer Epithelium – atrophic Necrosis of epithelium – oral ulcer

34. Lichenoid dermatitis involving contiguous follicular infundibula ( 40X) Orthokeratosis Acanthosis Papillomatosis Wedge shaped hypergranulosis , lichenoid lymphocytic infiltrate at base of infundibulum, few colloid bodies at dermo- epidermal junction (400X) Hypertrophic LP

35. Lichen planopilaris.flask like dilated follicular infuldibula with compact keratin - Follicular plugging, hypergranulosis , and dense , bandlike perifollicular lymphocytic infiltrate (destroys bulge cells ) that obscures the infundibular epithelium . Lichen planopilaris , developed lesion. Perifollicular fibrosis and inflammation with epithelial atrophy at the infundibuloisthmic portion give rise to an hourglass configuration. loss of follicles

36. Clumps of numerous colloid bodies in upper papillary dermis with numerous M elanophages ,vacuolar interface dermatitis - Lichen planus pigmentosus

37. DD for LP Lichenoid drug eruptions Lichenoid GVHD - Langehans cells decreased , cytotoxic T infiltate in epidermis Early - perivascular sparse infiltrate Late – dermal sclerosis Lichenoid LE Lichen planus like keratoses -“Focal parakeratosis and adjacent solar lentigines ” Early SCC in situ – dysplastic keratinocytes

38. Lichenoid drug eruption : histologic presentation can be identical to LP Differentiating features F ocal pararkeratosis Absence of granular layer necrotic keratinocytes in all layers of the epidermis Deeper perivascular infiltate with numerous e osinophils ,sometimes plasma cells

39. Lichenoid LE a ) atrophy of the epidermis in addition to acanthosis , ( b) absence of eosinophilia of the keratinocytes in the spinous layer, ( c) a superficial bandlike infiltrate with a superficial and deep perivascular and periadnexal infiltrate, ( d) the presence of a thickened, PAS-positive basement membrane , and ( e) dermal mucin deposits. Direct immunofluorescence findings LE - linear or granular deposits of immunoglobulins and C3 predominate in lesional skin, LP - clusters of necrotic keratinocytes with absorbed immunoglobulins and complement are found Langerhans cells decreased in number – DLE and SLE increased in early lichen planus

40. Lichenoid pigmented purpura. There is a band-like lymphocytic infiltrate that does not obscure the dermoepidermal junction (A). Extravasated erythrocytes and/or hemosiderin-laden macrophages are a prominent feature (B and C).

41. D ense lymphohistiocytic infiltrate filling the expanded dermal papillae with thin suprapiallary epidermis with basal cell vacular alteration and focal parakeratosis . At each lateral margin of the infiltrate, rete ridges tend to bend downward and inward and seem to clutch the infiltrate Claw clutching ball sign Cluster of round, flat-topped, flesh-colored papules of a few millimeters in diameter . Lichen nitidus

42. Lichen striatus. There is a dense superficial and deep perivascular , perieccrine and periadnexal lympho histiocytic infiltrate with a band-like component that obscures the dermoepidermal junction (A). Shows psoriasiform hyperplasia of epidermis Foci of mild to moderate spongiosis and may show exocytosis of lymphocytes (B). Linear band of confluent “small papules following a Blaschko line

43. Lichen striatus Closer view shows an infiltrate of lymphocytes and histiocytes , exocytosis of lymphocytes, acanthosis , spongiosis , and focal parakeratosis Superficial and deep perivascular, perieccrine , and perifollicular infiltrate of lymphocytes and histiocytes that extends to the epidermis, which shows acanthosis and spongiosis .

44. Lichen sclerosus et atrophicus (LS et A), atrophy, follicular plugging, papillary dermal edema, and sclerosis with a patchy, band-like predominantly lymphocytic infiltrate interposed between the altered collagen of the upper dermis and normal collagen of lower dermis (A and B). Fully developed LS et A. There is effacement of rete ridge pattern of epidermis with vacuolar alteration of basal keratinocytes and sclerosis of dermis (C)

45. Superficial and deep perivascular and periadnexal lymphocytic infiltrates . T hin epidermis, basal cell vacuolization with subepidermal clefts that involve follicular infundibular epithelium, follicular plugging at one end of the sections. LE Pools of bluish-grey mucin between bundles of collagen in reticular dermis. LE

46. Systemic lupus erythematosus. There is obscuration of the dermoepidermal junction with vacuolar alteration of the basal keratinocytes with a sparse lymphocytic infiltrate (A and B). Dermatomyositis. This may appear identical to systemic lupus erythematosus. There is a sparse lymphocytic infiltrate with vacuolar alteration of the basal keratinocytes & less dermal mucin C ). Abundant mucin interposed between the dermal collagen bundles -SLE (D )

47. Discoid lupus erythematosus. There is a superficial and deep perivascular and periadnexal lymphocytic infiltrate with vacuolar alteration of the basal keratinocytes (A and B). A dense lymphocytic infiltrate surrounds the follicular adnexae with obscuration of the epithelial-stromal junction(C). Note the marked thickening of the basement membrane (D)

48. Tumid LE – D/D Differentiating features 1.Lymphocytic lymphoma atypical lymphocytes interstitial distribution (“ Indian filing ”), and Do not surround pilosebaceous units 2.Lymphocytoma cutis Heavier infiltrate Interstitial component, Do not surround pilosebaceous units Often contains an admixture of larger, paler lymphocytes arranged in lymphoid follicles, mimicking germinal center formation 3.plaque type of polymorphous light eruption prominent band of papillary dermal edema. The infiltrate is more intense in the superficial dermis than in deep dermis and is occasionally admixed with neutrophils. No folliculocentric arrangement and No stromal mucin deposition 4.Jessner lymphocytic infiltration of the skin plasma cells and mucin are absent. presence of increased numbers of B lymphocytes in the infiltrate 5.Lues 6.Lyme’s disease IHC , silver stain No mucin deposition

49. Pityriasis lichenoides et varioliformis acuta (PLEVA). There is a superficial and deep perivascular lymphocytic infiltrate that obscures dermoepidermal junction (A ) , vacuolar basal cell degeneration . Neutrophils are in stratum corneum admixed with degenerated necrotic keratinocytes and parakeratotic corneocytes , intra and intercellular edema necrosis ( B). Necrotic keratinocytes are scattered throughout epidermis and melanophages and erythrocytes are interposed between keratinocytes (C).

50. Superficial perivascular lymphocytic infiltrate, SUBTLE VACUOLAR ALTERATIONS, +/- EXTRAVASTED RBC . Note the thick wafer-like scale containing flat parakeratosis and flecks of melanin. Pityriasis lichenoides chronica

51. D/D for PLEVA and PLC Pityriasis rosea Vesicular insect bites Numerous eosinophils i n a vertically oriented dermal infiltrate are more commonly seen in insect bites Subacute eczematous dermatitis PLEVA vs PR, subacute eczema The presence of a deeper inflammatory infiltrate, extensive epidermal necrosis, and the absence of intraepidermal spongiotic microvesicles Guttate psoriasis Lymphomatoid papulosis

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