120: Cutaneous Pseudolymphoma Flashcards
What is cutaneous pseudolymphoma?
Cutaneous pseudolymphoma is a group of skin diseases characterized as benign lymphoproliferative processes that clinically and/or histologically simulate cutaneous lymphomas.
What are the infectious agents that can cause cutaneous pseudolymphoma?
Infectious agents include spirochetal bacteria (e.g., Borrelia burgdorferi, Treponema pallidum), viruses (e.g., parapoxviruses), infestations (e.g., scabies, insect bites), injection of vaccines and allergens for hyposensitization, foreign bodies (e.g., tattoos, metals), drugs, and idiopathic causes.
What are the classifications of cutaneous pseudolymphoma?
The classifications include: 1. Nodular PSL simulating clinically and histologically T-cell or B-cell lymphoma 2. PSLs mimicking histologically mycosis fungoides (pseudo-MF) 3. Other skin disorders with lymphocyte-rich infiltrates 4. Benign intravascular proliferation of lymphocytes (simulating intravascular lymphoma).
What is the diagnostic approach for cutaneous pseudolymphoma?
The diagnostic approach includes clinical presentation, histologic analysis, molecular studies, and diagnostic workup.
What is the clinical course of cutaneous pseudolymphoma?
The clinical course is highly variable: resolution may occur after biopsy, some lesions may persist for months or years, and recurrences can occur, especially after reexposure to the inducing agent.
What are the treatment options for nodular pseudolymphoma?
Treatment options include complete surgical excision, topical or intralesional corticosteroids, cryotherapy, or laser therapy. If not successful, radiation therapy may be considered.
What are the common clinical features of cutaneous B-cell pseudolymphoma?
- Most commonly presents with a nodule or plaque.
- Commonly involved sites include the face, especially the nose and cheeks, upper trunk, and arms.
- Male-to-female ratio is 2:1.
- Approximately 67% of patients are younger than 40 years, with less than 10% being children and adolescents.
- Most common presentation is a localized form with a solitary nodule measuring up to 4 cm.
What histological features are characteristic of nodular B-cell pseudolymphoma?
- Dense nodular infiltrate predominantly located in the reticular dermis.
- Composed mostly of small lymphocytes with chromatin dense nuclei.
- Presence of reactive germinal centers with tingible body macrophages.
- Lymphocytes do not show nuclear atypia.
- Admixture of plasma cells, which are diffusely scattered.
- Possible presence of eosinophils and a granulomatous component in some cases.
What immunophenotyping characteristics are observed in cutaneous B-cell pseudolymphoma?
- Majority of the infiltrate consists of CD19+, CD20+, and CD79a+ B cells.
- Reactive follicles show (+) bcl-6 and (-) bcl-2.
- Small B cells in the interfollicular area show (-) bcl-6 and (+) bcl-2.
- Networks of CD21+ follicular dendritic cells are sharply demarcated and regularly structured.
What are the differential diagnoses for cutaneous B-cell pseudolymphoma?
Diagnosis | Key Features |
|———–|————–|
| Primary cutaneous marginal zone lymphoma (PCMZL) | - Nodular infiltrates in the reticular dermis and superficial subcutis.
- Plasma cells are more prominent and found in sheets.
- Monotypic expression of Ig light chains with a ratio of at least 5:1. |
| Primary cutaneous follicle center lymphoma (PCFCL) | - Predominance of centrocyte-like differentiated tumor cells.
- Low proliferative activity in neoplastic follicles.
- Clonal B-cell population detected in the majority of cases. |
What are the potential etiological factors associated with cutaneous pseudolymphoma?
- Borrelia burgdorferi infection, insect bites, or injection of vaccines or antigens for hyposensitization.
- Acupuncture treatment, tattoos, metals in piercing rings and earrings, and drugs.
What is the clinical significance of pseudoclonality in B-cell pseudolymphomas?
Pseudoclonality represents a diagnostic pitfall and must be ruled out in lesions with subtle infiltrates to avoid misdiagnosis.
What histological features differentiate primary cutaneous follicle center lymphoma (PCFCL) from B-cell pseudolymphoma (PSL)?
PCFCL shows predominance of centrocyte-like differentiated tumor cells, low proliferative activity in neoplastic follicles, and irregular networks of CD21+ follicular dendritic cells. B-cell PSLs have high proliferative activity in reactive germinal centers, sharply demarcated CD21+ networks, and readily identifiable tingible body macrophages.
What is the role of hydroxychloroquine in treating multiple pseudolymphoma lesions?
Hydroxychloroquine inhibits the activity of plasmacytoid dendritic cells, which are found in the majority of B-cell pseudolymphomas and may drive the condition.
What is the clinical presentation of lymphocytoma cutis?
Lymphocytoma cutis presents with a solitary nodule or plaque, often on the face, upper trunk, or arms, with a male-to-female ratio of 2:1.
A patient presents with a solitary red to violaceous dome-shaped nodule on the earlobe. What is the likely diagnosis and the associated pathogen?
The likely diagnosis is Borrelia-associated B-cell pseudolymphoma, caused by Borrelia burgdorferi infection.
What is the first-line therapy for Borrelia-associated B-cell pseudolymphomas?
Antibiotics are the first-line therapy for Borrelia-associated B-cell pseudolymphomas, which help prevent other complications from Borrelia infection, such as arthritis and carditis.
What are the clinical features of T-cell and mixed pseudolymphoma?
T-cell and mixed pseudolymphoma usually presents with a solitary or multiple red to violaceous nodules similar to B-cell pseudolymphoma.
What is the significance of clonality studies in T-cell pseudolymphomas?
Clonality studies show a polyclonal infiltrate in the majority of T-cell pseudolymphomas, while clonal pseudolymphomas may progress to overt lymphoma and represent very early stages of lymphomagenesis.
What are the differential diagnoses for cutaneous T-cell pseudolymphoma?
Differential diagnoses include: 1. Cutaneous CD4+ small-/medium-sized T-cell lymphoma - solitary lesion, indolent course. 2. Mycosis fungoides (MF) - presents with patches and plaques preceding tumors. 3. Secondary cutaneous infiltrates of angioimmunoblastic T-cell lymphoma (AITL) - associated with Epstein-Barr virus and B symptoms. 4. Lupus erythematosus (tumidus type) - characterized by vacuolization at the hair follicle epithelium.
What laboratory findings are associated with T-cell pseudolymphoma?
Histological findings include dense nodular infiltrate extending throughout the entire dermis, rare germinal centers and granuloma formation, exocytosis of T lymphocytes into the hair follicle epithelium, and no significant exocytosis of lymphocytes into the overlying interfollicular epidermis.
What is the first-line treatment for Borrelia-associated B-cell pseudolymphoma?
The first-line treatment is antibiotics to prevent complications such as arthritis and carditis.
What is the clinical presentation of nodular T-cell pseudolymphoma?
Nodular T-cell pseudolymphoma presents with solitary or multiple red to violaceous nodules, often with a dense dermal T-cell–rich infiltrate.
What are the histological features of CD30+ T-cell pseudolymphoma?
Histological features include medium-sized to large CD30+ blast-like cells scattered throughout a T-cell–rich infiltrate.
What are the histological features of Pseudolymphomatous Folliculitis?
- 50% with features of nodular B-cell PSLs and 50% with features of nodular T-cell PSLs.
- Lymphocytic infiltrates are located throughout the entire dermis and may extend into the subcutis, arranged around the hair follicles.
- Grenz zone may be present.
- Exocytosis of lymphocytes into the hair follicles often showing broadened epithelia.
- 50% with atypical lymphocytes are found. Half of the cases harbor aggregates of histiocytes.
- Admixture of numerous dendritic cells with expression of CD1a and S-100 was identified in all cases.
What are the clinical manifestations of persistent nodular arthropod bite reactions?
- Longstanding pruritic papules and nodules, red-brown and may be excoriated.
- Areas of predilection include elbows, trunk, genitalia, axillary, and inguinal folds.
- Mites or scybala are rarely found in the epidermis overlying the dense dermal lymphocytic infiltrates.
- Delayed-type hypersensitivity reaction is considered to be the underlying trigger factor for the formation of the T-cell–rich infiltrates.
What is the differential diagnosis for persistent arthropod bite reactions?
- Persistent arthropod bite reactions have to be differentiated from exaggerated bite reactions, which occurs in B-cell CLL and other leukemias.
- Lymphomatoid papulosis (Type A), Hodgkin lymphoma, and nodular secondary syphilis are histologically differential diagnoses.
- Lesions may be longstanding and persist for several months.
- Antiscabietic treatment is ineffective.
What treatment options are available for nodular arthropod bite reactions if spontaneous regression does not occur?
- Excision.
- Intralesional corticosteroids.
- Topical immunomodulators may be considered if spontaneous regression does not occur or topical steroids are ineffective.
What are the histological features of nodular scabies?
Histological features include a wedge-shaped dermal infiltrate predominantly composed of small lymphocytes, eosinophils, and occasional plasma cells, with features of pruriginous reaction in the epidermis.
A patient presents with longstanding pruritic papules and nodules on the elbows and trunk. Histology shows a wedge-shaped dermal infiltrate with eosinophils. What is the diagnosis?
The diagnosis is persistent nodular arthropod bite reactions.
What histological features are characteristic of pseudolymphomatous folliculitis?
Histological features include lymphocytic infiltrates throughout the dermis, exocytosis of lymphocytes into hair follicles, and broadened epithelia.
What is the clinical presentation of pseudolymphomatous folliculitis?
Pseudolymphomatous folliculitis presents with a solitary nodule on the face, measuring less than 1.5 cm, or a miliarial form with papules.
What is the clinical presentation of persistent nodular arthropod bite reactions?
Persistent nodular arthropod bite reactions present with longstanding pruritic papules and nodules, often on the elbows, trunk, and genitalia.
A patient with a history of tattooing develops papules limited to areas with red tattoo dye. What is the likely diagnosis and the causative agent?
The likely diagnosis is pseudolymphoma associated with tattoos, caused by a delayed-type hypersensitivity reaction to cinnabar (mercuric sulfide) in the red tattoo dye.
What is the treatment for pseudolymphoma caused by leech therapy?
Treatment involves addressing the underlying cause, such as bacterial transfer from leeches, and may include antibiotics or other supportive measures.
What are the histological features of pseudolymphoma at drug and vaccine injection sites?
Histological features include B-cell–rich infiltrates with reactive germinal centers and histiocytes with granular gray-blue cytoplasm.
What are the histological features of pseudolymphoma caused by drugs?
Histological features include typical nodular T-cell or B-cell patterns with subtle nuclear atypia and low proliferation rates.
What are the histological features of cutaneous pseudolymphoma?
- Lichenoid component with a band-like superficial infiltrate.
- Interface changes and exocytosis of lymphocytes.
- Deeper lymphocytic infiltrate in the mid and deep dermis with a mixture of eosinophils, leading to a pseudolymphomatous appearance.
What are the differential diagnoses for cutaneous pseudolymphoma?
Diagnosis | Characteristics |
|———–|—————–|
| CD8+ MF | Predominantly CD8+ infiltrate |
| Sézary syndrome | Similar features to cutaneous pseudolymphoma |
| Cutaneous CD8+ aggressive epidermotropic T-cell lymphoma | Loss of pan T-cell markers |
| Lymphomatoid papulosis | Types D and E with specific features |
What is lymphomatoid contact dermatitis (LCD) and its clinical features?
LCD is a chronic contact dermatitis that histologically simulates mycosis fungoides (MF). Clinical features include pruritic eczematous erythematous and scaly papules, patches, plaques, and, in rare cases, erythroderma.
What are the treatment options for lymphomatoid contact dermatitis?
- Avoidance of exposure to the allergen.
- Topical corticosteroids or topical immunomodulators.
- UV light–based strategies.
- Systemic immunosuppression may be effective.
What is the significance of CD30+ lymphocytes in the context of infections that simulate lymphoma?
CD30+ lymphocytes can appear enlarged and atypical in infections like herpes virus and varicella zoster virus, which can be mistaken for lymphoma infiltrates.
How can lymphomatoid contact dermatitis be differentiated from mycosis fungoides (MF)?
Lymphomatoid contact dermatitis shows variable spongiosis, lack of significant lymphocyte atypia, inconspicuous CD4-to-CD8 ratio, and absence of T-cell marker loss, unlike MF.
What histological features are seen in cutaneous leishmaniasis that mimic lymphoma?
Histological features include a nodular infiltrate composed of numerous lymphocytes, plasma cells, and histiocytes, but lack nuclear atypia.
What are the histological features of lymphomatoid contact dermatitis?
Histological features include a superficial band-like infiltrate with variable exocytosis of lymphocytes, spongiosis, and pseudo-Pautrier collections.
What are the histological features of pseudolymphoma caused by tattoos?
Histological features include a lichenoid component with a band-like superficial infiltrate, interface changes, and exocytosis of lymphocytes.
What are the histological features of lymphomatoid drug eruptions?
- Band-like infiltrate in the upper dermis
- Variable degrees of exocytosis of lymphocytes
- Possible vacuolar alteration at the DEJ and apoptotic keratinocytes
What are the clinical findings associated with actinic reticuloid?
- Middle-aged and older men
- Persistent erythematous lichenoid papules and plaques on light-exposed skin areas
- Intense pruritus
- Affected areas include face and neck, leading to a facies leonina-like aspect
- Progression into erythroderma and possible lichenification and erosions over time
What is the differential diagnosis for lymphomatoid drug eruptions?
- Epidermotropic CTCL, particularly MF and Sézary syndrome
- Distinction from CD8+ MF (patches and plaques)
- CD8+ lymphomatoid papulosis (especially Type D or Type E)
- PLEVA
- Lymphoma with remarkable nuclear atypia
What are the treatment options for lymphomatoid drug eruptions?
- Withdrawal of the drug
- Systemic, intralesional, or topical steroids for treatment
- Lymphomatoid drug eruption can persist for several months
- Reexposure to the drug may elicit a relapse of the PSL
What laboratory tests are used to diagnose actinic reticuloid?
- Histology shows:
- Psoriasiform hyperplasia of the epidermis
- Slight spongiosis and compact orthokeratosis with focal parakeratosis
- Upper dermis with perivascular and interstitial infiltrate
- Papillary dermis with coarse bundles of collagen arranged in vertical streaks
- Lymphocytes may show slightly atypical nuclei and exocytosis into the overlying epidermis
- Immunohistochemistry shows predominance of CD8+ T cells and increased CD8+ T cells in peripheral blood
What are the histological features of actinic reticuloid?
Histological features include psoriasiform hyperplasia, slight spongiosis, compact orthokeratosis, and a dermal infiltrate with CD8+ T cells.
What is the clinical presentation of lymphomatoid drug eruptions?
Lymphomatoid drug eruptions present with nodular, maculopapular, or papular eruptions, often persisting for months after drug withdrawal.
What are the clinical features of actinic reticuloid, and how does it differ from Sézary syndrome?
Actinic reticuloid presents with persistent erythematous lichenoid papules and plaques on light-exposed areas, intense pruritus, and a facies leonina-like aspect. It differs from Sézary syndrome by lacking nuclear atypia of lymphocytes and circulating atypical lymphocytes.
What is the clinical course and prognosis of CD8+ T-cell pseudolymphoma in immunodeficiency?
- Longstanding highly chronic course.
- Bad overall prognosis: severe lymphopenia of CD4+ T cells.
- Indolent course in most patients.
- Remission can occur with highly active antiretroviral therapy and methotrexate in moderately immunosuppressed patients.
What are the histological features of papuloerythroderma Ofuji?
- Eczematous features with acanthosis, spongiosis, and hyperparakeratosis.
- Dermal lymphocytic infiltrate with admixture of plasma cells, eosinophils, and neutrophils.
- Exocytosis of neutrophils and eosinophils may be observed.
How can papuloerythroderma Ofuji be distinguished from Sézary syndrome?
Papuloerythroderma Ofuji lacks nuclear atypia of the lymphocytes and circulating atypical lymphocytes, which are present in Sézary syndrome.
What are the treatment options for papuloerythroderma Ofuji?
- UV light treatment including psoralen and ultraviolet A (PUVA).
- Bath PUVA, UV-B in combination with topical steroids, retinoids, Re-PUVA, oral steroids, and cyclosporine.
- Good prognosis if there is no underlying malignancy.
What are the clinical manifestations of Borrelia-associated T-cell pseudolymphoma?
- Most commonly manifests with B-cell–predominant infiltrates.
- Lymphocytoma cutis with plasma cells.
- Dermal T-cell infiltrate may be band-like or diffuse.
- Displayed focal epidermotropism with lining-up of lymphocytes along the junctional zone.
What is the significance of detecting clonal T-cell populations in inflammatory skin diseases?
Clonal T-cell populations may represent a predominance of T-cell clones in an immunologic reaction and are not sufficient to diagnose cutaneous T-cell lymphoma (CTCL).
What are the histological features of papuloerythroderma of Ofuji?
Histological features include eczematous features with acanthosis, spongiosis, hyperparakeratosis, and a dermal lymphocytic infiltrate with plasma cells, eosinophils, and neutrophils.
What is the clinical presentation of papuloerythroderma of Ofuji?
Papuloerythroderma of Ofuji presents with disseminated solid papules, often coalescing into flat-topped brownish plaques, sparing abdominal furrows (deckchair sign).
What percentage of clonal T cells is found in lichen planus?
6% clonal T cells are found in lichen planus.
What is the histological feature of lymphocytic infiltration of the skin Jessner-Kanof (LIS)?
LIS is characterized by an infiltrate composed of CD8+ lymphocytes.
What are the clinical features of acral pseudolymphomatous angiokeratoma?
It manifests as a unilateral eruption of clustered red to violaceous angiomatous papules (1 to 5 mm) on acral sites, with coalescing lesions and possible longitudinal splitting of nails, onycholysis, and nail deformities.
What is the management approach for lymphoplasmacytic plaque?
Management includes destruction of the lesions by curettage, intralesional corticosteroids, or high-potency topical corticosteroids under occlusion.
What is the tendency for relapses in lymphocytic infiltration of the skin and palpable arciform migratory erythema?
There is a tendency for relapses in both conditions.
What is the clinical presentation of palpable arciform migratory erythema of Clark (PAME)?
PAME presents as infiltrated annular erythema developing into large migrating lesions, predominantly on the trunk.
What is the clinical presentation of Jessner-Kanof lymphocytic infiltration of the skin?
Jessner-Kanof presents with infiltrates composed of CD8+ lymphocytes, often responding to topical steroids, oral antibiotics, and UVA1 therapy.
What is the clinical presentation of acral pseudolymphomatous angiokeratoma of childhood (APACHE)?
APACHE manifests as a unilateral eruption of clustered red to violaceous angiomatous papules on acral sites, with possible nail deformities.
What are the clinical features of cutaneous plasmocytosis?
- Multiple, brownish, small plaques and nodules occurring all over the body.
- Histology shows dermal infiltrates composed predominantly of mature polyclonal plasma cells.
- In some patients, signs of systemic involvement may include lymphadenopathy, hepatosplenomegaly, and hypergammaglobulinemia.
What is the histological finding in inflammatory pseudotumor?
- Circumscribed nodular infiltrate of small lymphocytes.
- Numerous plasma cells arranged in sheets.
- Histiocytes found in plasma cell granuloma.
- Reactive germinal centers may be found.
- Prominent spindle-cell component of myofibroblasts with expression of ALK (anaplastic lymphoma kinase).
What is the differential diagnosis for cutaneous plasmocytosis?
- Primary cutaneous plasmocytosis
- Lymphocytoma cutis
- Cutaneous marginal zone lymphoma
- Primary and secondary cutaneous plasmocytoma
- Infections (e.g., fungal, mycobacterial, treponemal)
What are the characteristics of angiolymphoid hyperplasia with eosinophilia?
- Represents a proliferation of blood vessels with prominent endothelia.
- Accompanied by a dense infiltrate of T-cells and B-cells in conjunction with eosinophils.
- Angioproliferative process resulting from the presence of bizarrely shaped blood vessels and epithelioid endothelia, leading to its alternative designation as epithelioid hemangioma.
What is the first-line treatment for longstanding plaque in cutaneous pseudolymphoma?
Surgical excision is the first-line treatment for longstanding plaque in cutaneous pseudolymphoma.
What are the histological features of Kimura disease?
Histological features include lymphoid components with germinal centers predominating over vessel proliferation, accompanied by peripheral blood eosinophilia.
What are the histological features of inflammatory pseudotumor?
Histological features include a circumscribed nodular infiltrate of small lymphocytes, numerous plasma cells, and histiocytes, with reactive germinal centers.
What are the histological features of lymphoplasmacytic plaque (LPP)?
Histological features include a dense dermal lymphohistiocytic infiltrate with numerous polyclonal plasma cells and interstitial histiocytic granulomas.
What are the clinical features of cutaneous plasmacytosis?
Cutaneous plasmacytosis presents with multiple brownish plaques and nodules, often associated with systemic involvement like lymphadenopathy and hypergammaglobulinemia.
What are the histological features of inflammatory pseudotumor?
Histological features include a nodular infiltrate of small lymphocytes, numerous plasma cells, and histiocytes, with reactive germinal centers.
What are the clinical features of ALHE in cutaneous pseudolymphoma?
- Angiomatous pink to red-brown papules or nodules
- Most commonly found on the head, neck, face, and ears, but also occurring at the extremities and genital area
- Lesions may be asymptomatic or associated with pruritus, pain, or bleeding
What histopathological features are associated with ALHE and Kimura disease?
- Dermal and/or subcutaneous nodules composed of a proliferation of postcapillary vessels and a dense lymphocytic infiltrate
- Endothelial cells with a round or oval nucleus and abundant eosinophilic cytoplasm
- Clonal T cells detected in both ALHE and Kimura disease
- Immunohistochemistry shows expression of CD31 and ERG by the endothelium, but no reactivity for podoplanin/D2-40
What is the prognosis and treatment for ALHE lesions?
- No spontaneous regression of ALHE lesions
- Recurrences are common, particularly after surgical resection
- Treatment options include surgery, cryotherapy, laser ablation, MTX, and IFN-α
- Arteriovenous shunt may be removed via embolization
What are the two variants of Castleman disease?
- Hyaline vascular type
- Plasma cell variant (associated with POEMS syndrome)
Hyaline vascular type:
- Small lymphocytes surrounding germinal centers in a concentrically whorled pattern
Plasma cell variant:
- Large follicles and an interfollicular zone rich in blood vessels and plasma cells
What differentiates benign intravascular proliferation of lymphocytes from intravascular lymphoma?
- Benign intravascular proliferation of lymphoid blasts occurs with or without expression of CD30 and arises in areas with inflammatory skin diseases or trauma.
- Intravascular lymphoma is an aggressive lymphoma with various phenotypic forms (B cell, T cell, or natural killer/T cell).
- Clonality studies reveal the polyclonal nature of benign intravascular proliferation, while intravascular lymphoma shows different characteristics.
What are the clinical features of Castleman disease?
Castleman disease presents with benign lymphoproliferative disorders, including hyaline vascular and plasma cell variants, and may involve lymph nodes or extranodal sites.
What are the clinical features of angiolymphoid hyperplasia with eosinophilia (ALHE)?
ALHE presents with angiomatous pink to red-brown papules or nodules, commonly on the head, neck, face, and ears, and may be associated with pruritus, pain, or bleeding.
What is the treatment for angiolymphoid hyperplasia with eosinophilia (ALHE)?
Treatment options include surgery, cryotherapy, laser ablation, methotrexate, interferon-alpha, and removal of arteriovenous shunts via embolization.
