Lung Mass: Diagnosis
SURGICAL/CLINICAL CONSIDERATIONS
Goal of Consultation
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Provide or confirm diagnosis on lung mass
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If malignant, margin of specimen should be evaluated
Change in Patient Management
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If diagnosis of malignancy is made, additional surgery may be performed to achieve tumor-free margins &/or stage tumor
Clinical Setting
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Small masses (< 1 cm) are frequently detected by imaging
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Excision is often necessary for diagnosis
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˜ 70% are primary lung malignancies
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˜ 10% are metastases to lung
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˜ 20% are nonmalignant lesions
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Large masses (> 2 cm) are generally diagnosed prior to surgery through transbronchial or CT-guided biopsy and do not necessarily require confirmation
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Adenocarcinomas with pure lepidic pattern on biopsy will likely need to be fully evaluated on permanent section to exclude invasive component
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SPECIMEN EVALUATION
Gross
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Masses may be excised by wedge resection, lobectomy, or pneumonectomy
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Pleural surface should be carefully inspected
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Adhesions: May be associated with inflammatory changes or invasion of tumor through pleura
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Puckering: Usually due to retraction by carcinoma that has invaded into, but not through, pleura
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Pleural invasion is used for staging and is important prognostic factor
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Lymphangitic spread: White color of pleural lymphatics indicating extensive lymphovascular invasion
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Specimen is palpated to identify site of all masses and relationship to any pleural changes
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Pleura will not move freely over carcinomas that have invaded into pleura
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Specimen is completely serially sectioned to reveal any palpated mass and smaller &/or less firm masses
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Any areas of possible pleural involvement should be preserved for later evaluation by permanent sections
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Size and location of all masses are recorded
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Distance of lesions to parenchymal margins and bronchial margins is recorded
Frozen Section
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Representative section of mass is frozen
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If lesion has “cheesy” or necrotic surface, touch preps may be indicated in lieu of frozen sections to avoid potential contamination of cryostat with infectious organism (e.g., Mycobacterium tuberculosis)
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If surgical margin is nearby, 1 section may be able to demonstrate both diagnosis and margin
Cytology
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Touch preps of cut surface of mass lesion may be helpful if conservation of tumor tissue for permanent section is necessary or if infectious granulomatous disease is possible
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Suspicion for lymphoma generally requires fresh tissue to be sent for additional ancillary testing (e.g., flow cytometry, cytogenetics)
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Presence of granulomas on touch prep from small necrotic mass suggests infectious etiology, and subsequent frozen section may not be indicated
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MOST COMMON DIAGNOSES
Adenocarcinoma: Conventional/Nonlepidic Pattern
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Most common diagnosis overall
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Morphology (glandular vs. solid) depends heavily on degree of differentiation
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Desmoplastic stroma or extensive chronic inflammatory response is often seen
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Morphologic variants (e.g., papillary, micropapillary, and solid with mucin production) are occasionally seen
Adenocarcinoma In Situ
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Synonymous term with pure lepidic pattern adenocarcinoma
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Many cancers previously termed bronchioloalveolar would be in this category
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By definition, mass must be < 3 cm to make this diagnosis
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Often presents as ground-glass opacity on chest x-ray
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Grossly forms ill-defined firmer area of lung parenchyma
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Lymphomas and focal pneumonia can have similar gross appearance
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This diagnosis should not be rendered without histologic evaluation of entire mass on permanent section to exclude invasion
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Multiple lesions may be present
Metastatic Carcinoma/Sarcoma
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Previous documented history of malignancy (e.g., colonic adenocarcinoma, osteosarcoma) is invaluable
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Metastatic disease to lung is more likely to present as multiple nodules rather than as single nodule
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Distinction between primary malignancy and metastasis may not always be possible at time of frozen section
Squamous Cell Carcinoma
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More likely to be centrally located than adenocarcinomas
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May have gritty cut surface depending on amount of keratin production by tumor
Carcinoid
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Most cases occur centrally, especially in endobronchial location
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Often bilobed with endobronchial component and component in bronchial wall
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Patients are generally younger than typical patient with lung carcinoma
Small Cell Carcinoma
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Rarely resected as many have metastasized at time of diagnosis
Non-Small Cell Carcinoma, Not Further Classified
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Acceptable diagnosis in setting of poorly differentiated large cell carcinoma for which thorough sampling &/or immunohistochemistry is necessary for precise classification
Chondroid Hamartoma
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Generally small and well circumscribed
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Typically demonstrates blue-gray glassy cut surface due to cartilaginous composition
Granuloma
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Usually small (< 1 cm) and round; may be multiple
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Cut surface varies from soft/necrotic to solid/firm to bony/rock hard
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Granulomas with necrotic/“cheesy” cut surface are more likely to contain fungi (e.g., Histoplasma) or mycobacteria, among other organisms
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Tissue should be kept sterile and sent for cultures
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Frozen sections should be avoided to minimize exposure of personnel to infectious agents and contamination of cryostat
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Other Nonneoplastic Inflammatory Changes
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Entities known to present with nodularities include abscess, organizing pneumonia (round pneumonia), granulomatosis with polyangiitis (Wegener granulomatosis), and hypersensitivity pneumonitis
Atypical Adenomatous Hyperplasia
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Incidental finding that should not create grossly identifiable mass lesion
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Size: < 5 mm in diameter
Lymphoma
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Most common are extranodal marginal zone lymphoma (lymphoma of mucosa-associated lymphoid tissue) and diffuse large B-cell lymphoma
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Tissue should be taken for special studies (e.g., special fixatives, frozen tissue, tissue for flow cytometry)
Intraparenchymal Lymph Node
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Often located near pleura and grossly black due to anthracotic pigment
REPORTING
Frozen Section
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Diagnosis of malignant or benign lesion is usually sufficient for intraoperative management
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Subtypes of carcinoma are not critical intraoperatively
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If patient has known primary carcinoma elsewhere, surgeon may want opinion as to whether lesion is likely metastasis or primary carcinoma
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Distinction may not be possible on frozen section
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PITFALLS
Lepidic Pattern Adenocarcinoma vs. Nonneoplastic Inflammatory Changes
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Primary distinction is by the more pronounced nuclear atypia in adenocarcinomas
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Adenocarcinoma is more likely to show nuclear inclusions
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Carcinomas generally have thicker septal walls
Metastatic Carcinoma vs. Primary Lung Carcinoma
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Important to know history of any prior malignant tumors and histologic type
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May not be possible to make this distinction on frozen section
Lymphoma vs. Intraparenchymal Lymph Node
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Lymphoma generally is larger with irregular border and lacks tan, fleshy cut surface of lymph node
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Histologic architectural hallmarks of lymph node (capsule, subcapsular sinus, etc.) should be sought if tissue is frozen
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Pure cytologic evaluation (i.e., touch prep only) may be of limited use depending on grade of lymphoma
Necrotic Malignancy vs. Necrotic Granuloma
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Distinction can be challenging if lesion is totally necrotic
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Malignancies (both primary and metastatic) are generally larger than infectious lesions
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Granuloma formation on touch prep or frozen section suggests infectious origin, but rare exceptions exist
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Tissue should be taken for cultures if infectious process is suspected
RELATED REFERENCES
1. Xu X et al: The accuracy of frozen section diagnosis of pulmonary nodules: evaluation of inflation method during intraoperative pathology consultation with cryosection. J Thorac Oncol. 5(1):39-44, 2010
2. Gupta R et al: What can we learn from the errors in the frozen section diagnosis of pulmonary carcinoid tumors? An evidence-based approach. Hum Pathol. 40(1):1-9, 2009
3. Herbst J et al: Evidence-based criteria to help distinguish metastatic breast cancer from primary lung adenocarcinoma on thoracic frozen section. Am J Clin Pathol. 131(1):122-8, 2009
4. Gupta R et al: Lessons learned from mistakes and deferrals in the frozen section diagnosis of bronchioloalveolar carcinoma and well-differentiated pulmonary adenocarcinoma: an evidence-based pathology approach. Am J Clin Pathol. 130(1):11-20; quiz 146, 2008
5. Myung JK et al: A simple inflation method for frozen section diagnosis of minute precancerous lesions of the lung. Lung Cancer. 59(2):198-202, 2008

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