Other Lymphoproliferative and Myeloproliferative Diseases

• A benign skin-limited disorder that overlaps with other entities, including dermal lupus erythematosus, cutaneous lymphoid hyperplasia, and polymorphic light eruption (PMLE).

• Males = females; onset typically during middle age; very rare in children.

• Most commonly appears on the head, neck, and upper back as one or several asymptomatic, erythematous papules, plaques (often annular) > nodules (Fig. 99.1); no secondary or surface changes (such as scale or crust).

• May last several weeks to months and will typically resolve spontaneously over months to years without sequelae.

• No systemic manifestations.

• DDx: see Fig. 99.2.

• Rx: watch-and-wait approach is often acceptable; if Rx desired, consider topical (class I) or intralesional CS; less often hydroxychloroquine is used.

• A benign, reactive lymphocytic proliferation that is thought to represent an exaggerated local immunologic reaction to a trigger that is usually unidentified.

• Females > males; adults > children.

• Inciting agents that have been reported include arthropod bites, tattoos, vaccinations, medications (e.g. antihistamines, antidepressants, angiotensin II receptor blockers), and in Europe, Borrelia burgdorferi infection.

• Presents most often on the head, neck, and upper extremities as one or several firm, erythematous to violaceous papules, plaques, or nodules (Fig. 99.3); usually no surface changes.

• Often spontaneously resolves without scarring.

• DDx (see Fig. 99.2): lymphocytic infiltrate of Jessner, lymphoma cutis, leukemia cutis, solid organ metastases, and occasionally adnexal tumors.

• Rx: topical (class I) or intralesional CS.

• Most commonly seen in neonates secondary to underlying bone marrow dysfunction; rarely in adults secondary to myelofibrosis, other myeloproliferative disorders or after splenectomy.

• Most often associated with TORCH (toxoplasmosis, other [e.g. parvovirus B19], rubella, cytomegalovirus) infections in neonates.

• Clinically presents with erythematous to violaceous papules and nodules > plaques, ulcers, or nasal polyps (Fig. 99.4).

• When widely disseminated (typically in neonates) it leads to the classic ‘blueberry muffin baby’ presentation (Table 99.1).

• Diagnosis is made by histopathology (dermal infiltrates of immature erythrocytes, leukocytes, and megakaryocytes).

• DDx: see Table 99.1 for neonates, leukemia cutis in adults.

• Rx: treat underlying bone marrow dysfunction; spontaneous resolution typically occurs in cases related to viral infections.

• Cutaneous lesions associated with both acute and chronic leukemias may be either (1) nonspecific reactive skin lesions (Table 99.2) or (2) specific infiltrates, called ‘leukemia cutis’.

• Leukemia cutis typically presents as erythematous to violaceous firm papules or nodules (Fig. 99.5); less often purpura, ulcers, and rarely bullae; lesions may be hemorrhagic due to thrombocytopenia.

• Favors head, neck, trunk, and sites of scars or trauma.

• Less common presentations of leukemia cutis: chloromas, gingival hyperplasia.

• In most patients with acute leukemia, cutaneous lesions (if present) appear at the time of diagnosis or recurrence.

• Occasionally, leukemia cutis antedates the appearance of leukemia in the peripheral smear (‘aleukemic leukemia cutis’); rarely predates apparent bone marrow involvement by months.

• DDx: lengthy list because of the protean clinical presentations of leukemia cutis, but may include lymphoma cutis, infectious emboli, vasculitis, drug eruptions, Sweet's syndrome and other neutrophilic disorders, extramedullary hematopoiesis.

• Rx: treat the underlying leukemia.

• Primary or isolated cutaneous HD is very unusual; typically presents as one or several ulcerated nodules and usually follows a more indolent course, with prognosis similar to those patients with early stage HD.

• Secondary cutaneous HD, occurring in patients with advanced systemic disease, constitutes the vast majority of cutaneous HD cases and as expected carries a worse prognosis.

• Secondary cutaneous HD usually presents with the rapid appearance of multiple, disseminated papulonodules and plaques, often on the trunk (Fig. 99.6), along with locations distal to affected lymph nodes.

• Previously referred to as ‘angioimmunoblastic lymphadenopathy’ (AILD).

• Now known to be the second most common peripheral T-cell lymphoma with the recent identification of the follicular helper T (T_FH) cell as the cell of origin.

• Unique in that it characteristically presents acutely with widespread, non-bulky lymphadenopathy; fever; and a diffuse, pruritic morbilliform eruption mimicking an acute viral infection or drug eruption.

• Other systemic findings include hepatosplenomegaly, polyclonal hypergammaglobulinemia, immune dysregulation resulting in autoantibody production (e.g. ANA, rheumatoid factor, antiphospholipid antibodies, false (+) Lyme serologies), cytopenias and hypereosinophilia.

• The morbilliform eruption and lymphadenopathy typically wax and wane, making suspicion and diagnosis of this malignancy even more elusive.

• The usual course is aggressive with a poor prognosis (median survival is <3 years); up to 30% may have longer-term survival.

• DDx: reactive lymphadenopathy due to a viral infection; drug eruption, infectious mononucleosis, or other systemic inflammatory diseases.

• Rx: combination chemotherapy; high-dose chemotherapy with autologous stem cell support; allogeneic stem cell transplantation, and newer immunomodulators.

• A rare, EBV-associated, angio-centric/destructive lymphoproliferative disorder that primarily affects the lungs, skin, and nervous system (less often the kidneys and gastrointestinal tract).

• Although previously classified as a reactive process, in most patients it represents a form of large B-cell lymphoma.

• LYG can be divided into grades 1, 2, or 3 depending on the proportion of CD20(+) large lymphoid cells.

• Most often seen in adults; males > females; can occur in the setting of immune dysfunction (e.g. Sjögren's syndrome, rheumatoid arthritis, renal transplantation, HIV infection).

• Frequently presents with cough, dyspnea, chest pain, fever, weight loss, malaise, arthralgia, and myalgia.

• Cutaneous lesions are present in ~25–50% of patients, usually ranging from nodules to ulcerated plaques (Fig. 99.7); rarely an exanthematous eruption develops.

• Typically follows an aggressive, fatal course with a 5-year mortality rate of 60–90%.

• DDx: other cutaneous lymphomas, infections (e.g. tuberculosis), pyoderma gangrenosum, medium vessel vasculitis, Wegener's granulomatosis, sarcoidosis.

• Rx: rituximab, multidrug chemotherapy, or perhaps interferon-α in earlier stage disease.