Definition
• Primary malignant melanoma of the lung with no evidence of other organ involvement and no history of previous melanoma or any prior atypical pigmented lesion
Clinical features
Epidemiology
• PPMM is extremely rare; most pulmonary melanomas are the result of metastasis from other sites
• Median age, 50 years; male predominance
Presentation
• Solitary, centrally located lesion, usually with an endobronchial component (metastatic melanomas are multiple and peripheral)
• Bronchoscopy may reveal characteristic pigmentation
Prognosis and treatment
• Prognosis is extremely poor: mean survival, 1.5 years
• Aggressive surgical resection with concurrent hilar and mediastinal lymphadenectomy and adjuvant chemotherapy may prevent recurrence and distant metastasis
Pathology
Histology
• Similar to melanoma in other sites, with large, polygonal, discohesive cells with prominent nucleoli and atypical melanocytic hyperplasia in overlying or nearby mucosa (junctional or lentiginous change)
• Lepidic spreading is a feature of metastatic melanoma
Immunopathology/special stains
• Positive staining for S100, Mart-1, Melan-A and HMB45
• Negative staining for keratin and neuroendocrine markers
Main differential diagnoses
• Pulmonary metastasis of malignant melanoma
• Poorly differentiated neoplasms including lymphoma and carcinoma
• Pigmented carcinoid tumor
• Clear-cell sugar tumor
• Melanocytic carcinoid tumor
Fig 1 Primary pulmonary malignant melanoma. Small nests of malignant cells are seen on this endobronchial biopsy. On immunohistochemical analysis, keratin stains were negative, which led to additional stains, of which S100 was strongly positive (stain not shown).
Fig 2 Primary pulmonary malignant melanoma. Resection specimen shows diffuse sheets of malignant cells at low power (A) and high power (B).
Extranodal Marginal Zone B-Cell Lymphoma Of Bronchial-Associated Lymphoid Tissue (Balt Lymphoma)
Definition
• The most common primary lung lymphoma; however, overall a rare cause of primary lung malignancy
Clinical features
Epidemiology
• Most patients are older than 50 years; slight female predominance
• May be seen in younger patients, especially if immunosuppressed
Presentation
• Asymptomatic pulmonary nodule(s) incidentally found on chest radiographs
• May have dyspnea, coughing, hemoptysis, fever, sweats, weight loss, or autoimmune disorder
• Monoclonal gammopathy and/or bone marrow involvement may be present
Prognosis and treatment
• Treated with local radiation therapy
• Indolent course with long disease-free intervals; however, may recur
• Widespread disease does not appear to confer a worse prognosis
• Rarely transforms to diffuse large B-cell lymphoma
Pathology
Histology
• Nodular interstitial infiltrate of lymphoma cells along bronchovascular bundles and interlobular septae (lymphangitic pattern)
• Sheets of infiltrating lymphoma cells can obliterate underlying lung architecture
• Reactive B-cell follicles with germinal centers surrounded by monomorphic marginal zone B cells with scant cytoplasm, small slightly irregular or cleaved nuclei, and inconspicuous nucleoli resembling centrocytes or small lymphocytes
• Less often, marginal zone B cells may have moderate amounts of cytoplasm and resemble monocytoid B cells or may have eccentric nuclei and plasmacytic differentiation
• Larger transformed cells with prominent nucleoli resembling centroblasts, plasma cells with Dutcher bodies, and small lymphocytes are usually present in small numbers
• Lymphoepithelial lesions, characterized by epithelial infiltration by lymphoma cells, are common
• Lymphoma cell infiltration of bronchial cartilage, pleura, or blood vessel walls may be present, and cells may extend into and widen alveolar septae
• Lymphoma cells may colonize follicles
• Amyloid deposition may be present
Immunopathology/special stains
• Lymphoma cells are positive for CD20, CD79a, PAX5, bcl2, and IgM
• Lymphoma cells are negative for CD10, CD23, cyclin D1, and bcl6
• CD5 is negative in the majority of cases
• CD21 is positive in the lymphoma cells and also highlights expanded follicular dendritic cell networks
• Most cases are kappa or lambda light chain restricted
Main differential diagnoses
• Malignant lesions
• Follicular lymphoma: CD10 positive
• Mantle cell lymphoma: cyclin D1 and CD5 positive
• Small lymphocytic lymphoma: CD5 positive and bcl2 negative
• Benign lesions: no light chain restriction, no immunoglobulin heavy chain rearrangement
• Nodular lymphoid hyperplasia: usually localized
• Follicular bronchiolitis: lacks lymphangitic spreading pattern
• Lymphoid interstitial pneumonia: immunosuppressed patients
Fig 1 Extranodal marginal zone B-cell lymphoma of bronchial-associated lymphoid tissue. At low power, BALT lymphoma has a nodular and lymphangitic pattern.
Fig 2 Extranodal marginal zone B-cell lymphoma of bronchial-associated lymphoid tissue. BALT lymphomas often invade beyond bronchial cartilage and infiltrate the airway epithelium.
Fig 3 Extranodal marginal zone B-cell lymphoma of bronchial-associated lymphoid tissue. High magnification of a lymphoepithelial lesion involving a bronchiole.
Fig 4 Extranodal marginal zone B-cell lymphoma of bronchial-associated lymphoid tissue. High magnification of BALT lymphoma cells invading a blood vessel wall.
Fig 5 Extranodal marginal zone B-cell lymphoma of bronchial-associated lymphoid tissue. The characteristic small cleaved cells of BALT lymphoma can be appreciated in a diffuse sheet and infiltrating the bronchial epithelium. Occasional larger centroblast-like cells with prominent nucleoli are also present.
Fig 6 Extranodal marginal zone B-cell lymphoma of bronchial-associated lymphoid tissue. An atrophic germinal center (lower right) is surrounded by a monomorphic population of small cleaved BALT lymphoma cells, which extend into and widen adjacent alveolar septae.
Fig 7 Extranodal marginal zone B-cell lymphoma of bronchial-associated lymphoid tissue. This touch preparation shows monotonous small lymphoma cells and rare larger cells with more abundant cytoplasm.
Fig 8 Extranodal marginal zone B-cell lymphoma of bronchial-associated lymphoid tissue. CD20 is strongly and diffusely positive in BALT lymphoma of the lung.
Fig 9 Extranodal marginal zone B-cell lymphoma of bronchial-associated lymphoid tissue. Kappa light chain restriction is demonstrated by in situ hybridization in this case of pulmonary BALT lymphoma.
Fig 10 Extranodal marginal zone B-cell lymphoma of bronchial-associated lymphoid tissue. In this case of BALT lymphoma of the lung, amyloid deposition is seen with this H&E stain as homogeneous eosinophilic material with cracking artifact (upper left).
Fig 11 Extranodal marginal zone B-cell lymphoma of bronchial-associated lymphoid tissue. Amyloid deposition is highlighted by a Congo red stain.