What cutaneous manifestations may be associated with Hodgkin lymphoma and non-Hodgkin lymphoma?

Cutaneous Manifestations Associated with Hodgkin and Non-Hodgkin Lymphoma

The cutaneous manifestations of lymphomas fall into two distinct categories: primary cutaneous lymphomas (which ARE the lymphoma itself presenting in skin) and paraneoplastic/secondary manifestations (which are reactive skin changes associated with systemic lymphoma). Understanding this distinction is critical for proper diagnosis and management.

Primary Cutaneous Lymphomas (Non-Hodgkin)

These represent lymphomas that originate in and remain confined to the skin, distinct from nodal lymphomas. Primary cutaneous lymphomas are the second most common extranodal non-Hodgkin's lymphomas, with 75% being cutaneous T-cell lymphomas (CTCL) and 25% cutaneous B-cell lymphomas (CBCL) 1.

Cutaneous T-Cell Lymphomas (CTCL)

Mycosis fungoides (MF) - The most common CTCL subtype:

• Patches and plaques that progress to tumors
• Variants include folliculotropic MF (follicular mucinosis with alopecia), pagetoid reticulosis (solitary hyperkeratotic patch/plaque), and granulomatous slack skin (diffusely infiltrated skin in groins/axillae) 1

Sézary syndrome (SS):

• Erythroderma (generalized redness of skin)
• Hyperkeratosis of palms and soles
• Lymphadenopathy and alopecia 1

Primary cutaneous CD30+ lymphoproliferative disorders:

• Solitary to localized nodules and tumors with or without ulceration
• Spontaneous regressions occur in 20% of cases
• Lymphomatoid papulosis presents as papular and papulonecrotic lesions that ulcerate during regression and heal with scarring 1

Subcutaneous panniculitis-like T-cell lymphoma:

• Solitary or multiple subcutaneous nodules to indurated plaque-like lesions 1

Extranodal NK/T-cell lymphoma, nasal type:

• Mid-facial destructive tumor
• Multiple plaques and tumors on trunk and extremities 1

Primary cutaneous peripheral T-cell lymphoma, unspecified:

• Disseminated eruptive patches, plaques and nodules with erosions, ulceration and necrosis 1

Cutaneous B-Cell Lymphomas (CBCL)

Primary cutaneous marginal zone B-cell lymphoma:

• Multiple red papules, plaques or nodules 1

Primary cutaneous follicle center lymphoma:

• Solitary or grouped plaques and tumors 1

Primary cutaneous diffuse large B-cell lymphoma, leg type:

• Red to bluish-red tumors, typically on legs in elderly patients 1

Primary cutaneous intravascular large B-cell lymphoma:

• Net-like reddish patches and plaques 1

Paraneoplastic/Secondary Cutaneous Manifestations

These are reactive skin changes associated with systemic Hodgkin or non-Hodgkin lymphoma, not direct lymphomatous infiltration.

Hodgkin Lymphoma Paraneoplastic Manifestations

The most common paraneoplastic manifestations in Hodgkin lymphoma are pruritus and eczema 2:

• Generalized pruritus - Present in 17 of 88 patients (19%) evaluated by dermatology in one series 2
• Eczema - The most common finding, present in 18 of 88 patients (20%) 2
• Erythema nodosum - Observed in 3 patients 2
• Exfoliative erythroderma - Can occur as part of the spectrum 3

Critical clinical point: Although pruritus is the most commonly recognized presenting symptom of Hodgkin lymphoma, new-onset eczema in adults should also be considered a warning sign deserving full lymph node examination, CBC with differential, and chest X-ray 2. Complete resolution of paraneoplastic syndromes is associated with significantly improved overall survival, and recurrence of cutaneous manifestations may indicate lymphoma relapse 3.

Non-Hodgkin Lymphoma Paraneoplastic Manifestations

Based on a study of 32 NHL patients, the statistically significant paraneoplastic manifestations were 4:

• Acquired ichthyosis - Present in 10 of 32 patients (31%)
• Generalized pruritus - Present in 5 of 32 patients (16%)
• Superficial fungal infections (7/32)
• Viral infections (2/32)
• Insect bite reactions and drug eruptions (less common)

Mycosis Fungoides Association with Hodgkin Lymphoma

An important and underrecognized association: mycosis fungoides was observed in 11 of 1049 patients (1%) with Hodgkin lymphoma, which is more than 290 times more common than in the general population 2. This represents a significant paraneoplastic phenomenon that clinicians must recognize.

Direct Cutaneous Extension (Rare)

Direct cutaneous involvement by extension from bulky lymphadenopathy is extremely rare and historically more common in Hodgkin disease than NHL 5. When it occurs in NHL, it's typically in aggressive subtypes like diffuse large B-cell lymphoma 5. This can even occur at sites of concurrent inflammation like cellulitis 6.

Clinical Algorithm for Evaluation

For patients with adult-onset pruritus or eczema:

1. Perform full lymph node examination
2. Order CBC with differential
3. Obtain chest X-ray
4. Consider additional imaging if lymphadenopathy detected 2

For patients with suspected cutaneous lymphoma:

1. Obtain detailed history and clinical observation
2. Perform skin biopsy with histologic analysis and appropriate immunohistochemical studies
3. Prove clonality in lesional skin (or peripheral blood if Sézary syndrome suspected)
4. Exclude other extranodal manifestations 1

Common pitfall: Many inflammatory skin diseases may reveal clonality by PCR, so clinical correlation is essential 1. The diagnosis requires extensive clinical experience and cannot rely on molecular testing alone.