Skin nontumor

Contributed by Pooja Rambhia, M.D. and Adele Shenoy, M.D.


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• Acute GVHD (Patterson: Weedon's Skin Pathology, 4th Edition, 2015)
  • Mild to moderate superficial perivascular lymphocytic infiltrate with exocytosis of inflammatory cells into the epidermis and basal vacuolation, interface dermatitis
  • Scattered, shrunken, eosinophilic keratinocytes with pyknotic nuclei, at all levels of the epidermis; often accompanied by 2 or more lymphocytes, producing the satellite cell necrosis - lymphocyte associated apoptosis
  • Occasionally, rare eosinophils can be present; melanin incontinence is prominent in patients with darker skin types
  • If severe, subepidermal microvesicles, subepidermal blisters and epidermal necrosis
  • Lymphocytic infiltrate in GVHD after solid organ transplantation is usually brisk in comparison to the sparser inflammation following bone marrow transplantation
• Chronic GVHD (Biol Blood Marrow Transplant 2015;21:589, Patterson: Weedon's Skin Pathology, 4th Edition, 2015)
  • Chronic lichenoid GVHD
    • Acanthosis, orthohyperkeratosis, parakeratosis with hypergranulosis
    • Underlying band-like lymphocytic infiltrate with basal layer vacuolization and apoptotic keratinocytes
    • Periadnexal inflammation can be present
    • May be difficult to distinguish from lichen planus without clinicopathologic correlation; satellite cell necrosis is the most helpful clue in GVHD biopsies to distinguish it from lichen planus
  • Chronic sclerodermoid GVHD
    • Dermal sclerosis (thickened compact collagen with loss of periadnexal fat)
    • Manifests with localized morphea-like features, diffuse sclerosis or lichen sclerosus-like features
    • Localized morphea-like features and diffuse sclerosis are largely confined to the reticular dermis or subcutaneous septa with little or no epidermal involvement
    • Lichen sclerosus-like GVHD: collagen alteration is confined to the papillary dermis (hyalinzation of the papillary dermis), often with residual interface changes characterized by the presence of mild vacuolar alteration, melanophages and sparse superficial perivascular lymphocytic infiltrate
    • In the fasciitis variant, biopsy specimens show only fibrous thickening of the fascia with adjacent inflammation without epidermal or dermal involvement
  • Rare variants: psoriasiform
    • Psoriasiform epithelial hyperplasia
    • Subtle vacuolar interface changes
    • Satellite cell necrosis (Am J Dermatopathol 2018;40:511)

Contributed by Silvija P. Gottesman, M.D. and Ohoud Aljarbou, M.D.

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• Acute GVHD
  • Drug reaction (J Am Acad Dermatol 2011;65:726):
    • Fewer or less conspicuous eosinophils than are seen in acute drug reaction
  • Viral infections (HHV6, HHV7, CMV) (Semin Cutan Med Surg 2007;26:155):
    • Look for viral inclusions (CMV) and other clinical clues
  • Eruption of lymphocyte recovery (Arch Dermatol 1989;125:1512):
    • Self limited; associated with transient fever
    • Unlike GVHD, no gastrointestinal or hepatic abnormalities
    • Histologically similar to acute GVHD
  • Acral erythema (palmoplantar erythrodysesthesia):
    • Complication of chemotherapy; affects palms and soles
    • Painful symmetrical edema and erythema, blistering and desquamation can happen
  • Toxic epidermal necrolysis (J Cutan Pathol 2017;44:857):
    • Very challenging to distinguish between this and severe GVHD - clinical correlation
  • Engraftment syndrome (Bone Marrow Transplant 2001;27:893):
    • Difficult to distinguish from GVHD; there is significant clinical and pathophysiologic overlap - clinical correlation is necessary
  • Radiation dermatitis (acute):
    • Cutaneous erythema, desquamation, blistering or necrosis
    • Histologically similar to acute GVHD - clinical correlation
  • Erythema multiforme:
    • Clinical picture: target and targetoid lesions are helpful to make a diagnosis
    • Histologically similar to acute GVHD
• Chronic GVHD
  • Lichen planus (Clin Dermatol 2005;23:285):
    • Lichenoid inflammatory infiltrate is not as dense
    • Flexural wrists and shins are classic locations for lichen planus
  • Lichenoid drug eruptions (J Cutan Pathol 2021;48:1480):
    • Features that are more predictive of a cutaneous drug eruption over GVHD included spongiosis, confluent parakeratosis and numerous eosinophils
    • Satellite cell necrosis is more common in GVHD
  • Pityriasis lichenoides chronica:
    • Overlapping histologic features - clinical correlation
    • Eosinophils are rare to absent in both conditions (J Cutan Pathol 2012;39:413)
  • Lichen sclerosus (Arch Dermatol 2002;138:924):
    • Overlapping histologic features - clinical correlation
  • Morphea / systemic sclerosis:
    • Distal to proximal progression of cutaneous sclerosis on the extremities is usually not seen in chronic GVHD
  • Eosinophilic fasciitis:
    • Clinical correlation
    • Chronic GVHD presenting as eosinophilic fasciitis is histologically indistinguishable from classic eosinophilic fasciitis (J Clin Rheumatol 2015;21:86)
  • Poikiloderma (dermatomyositis, systemic lupus erythematosus) (Lupus 2008;17:591):
    • Systemic lupus erythematosus and dermatomyositis may show dermal mucin, which is usually not present in GVHD

A 40 year old woman with a history of AML and status post-bone marrow transplant 2 months ago presented with fever and pruritic maculopapular eruption on palms and soles. Physical exam showed smooth and hyperkeratotic papules. Patient shares that at times she is noncompliant with taking her prescribed medications. Lately she has started using herbal supplements recommended by a friend. Punch biopsy from the foot was taken and microscopic exam showed mild vacuolar interface dermatitis with superficial perivascular lymphocytic infiltrate in the dermis and no eosinophils. Focally in the epidermis, eosinophilic degenerated keratinocytes surrounded by lymphocytes were noted. What is the most likely diagnosis?

1. Acute graft versus host disease
2. Chronic graft versus host disease
3. Drug reaction
4. HHV6 infection

A. Acute graft versus host disease. The patient has a history of bone marrow transplant, medication noncompliance and presents with a rash. Biopsy shows vacuolar interface dermatitis with superficial perivascular lymphocytic infiltrate in the dermis, no eosinophils and rare dyskeratotic keratinocytes. The combined clinical and morphologic features listed above are most consistent with acute graft versus host disease. Answer B is incorrect because chronic graft versus host disease would show lichenoid or sclerodermoid features. Answer C is incorrect because drug eruption would present with tissue eosinophilia. Answer D is incorrect because HHV6 infection shows nonspecific microscopic features.

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Reference: Graft versus host disease

A 30 year old man with a history of hematologic malignancy and bone marrow transplant 1 year prior presents to the dermatology clinic with erythematous and violaceous papules and plaques on the trunk, dorsal hands and forearms. Punch biopsy from the forearm showed vacuolar interface dermatitis with associated lichenoid inflammation in the papillary dermis, pigment incontinence and absence of eosinophils. Interface changes extend down follicular epithelia. What is the most likely diagnosis?

1. Chronic lichenoid graft versus host disease
2. Chronic sclerodermoid graft versus host disease
3. Lichenoid drug eruption
4. Lichen planus

A. Chronic lichenoid graft versus host disease. The patient presents with a rash and has a history of bone marrow transplant. Biopsy shows vacuolar interface dermatitis associated with lichenoid inflammation in the papillary dermis, pigment incontinence and absence of eosinophils. The combined clinical and morphologic features listed above are most consistent with chronic lichenoid graft versus host disease. Answer B is incorrect because chronic sclerodermoid graft versus host disease would show dermal sclerosis, which is absent in this case. Answer C is incorrect because lichenoid drug eruption would show prominent eosinophils, which are not appreciated here. Answer D is incorrect because lichen planus has characteristic clinical presentation of intensely pruritic papules and the inflammatory infiltrate is more prominent than in GVHD.

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Reference: Graft versus host disease

A 15 year old boy, day 47 post-bone marrow transplantation, presented with abrupt onset of diffuse erythematous papular eruption. Which of the following is the most likely diagnosis?

1. Discoid lupus erythematosus
2. Graft versus host disease
3. Pityriasis lichenoides chronica
4. Viral exanthema

B. Graft versus host disease. Biopsy shows epidermis with basal vacuolization and dyskeratotic keratinocytes. There is mild superficial dermal and perivascular lymphocytic infiltrate. The given clinical history along with the pathological findings support the diagnosis of graft versus host disease (GVHD). Answer A is incorrect because while discoid lupus erythematosus histologically can resemble GVHD (basal vacuolar interface change), it shows dermal mucin, which is usually absent in GVHD. Answer C is incorrect because while pityriasis lichenoides chronica and GVHD show similar histologic features, clinical correlation favors GVHD in this case. Answer D is incorrect because viral exanthem has nonspecific histologic findings, including spongiosis, perivascular lymphocytic infiltrate and sometimes lymphoexocytosis and necrotic keratinocytes in epidermis; eosinophils are usually absent. Clinically presents as a morbilliform rash. Clinical correlation and history of bone marrow transplant favors GVHD.

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Reference: Graft versus host disease