What are the diagnostic and management steps for a lung biopsy showing necrosis with atypical cells in the stroma?

Diagnostic and Management Approach for Lung Biopsy Showing Necrosis with Atypical Cells in Stroma

When a lung biopsy reveals necrosis with atypical cells in the stroma, this represents an inadequate sample that requires repeat biopsy with ultrasound or CT guidance to target viable tumor tissue in the peripheral rim, as necrotic centers yield nondiagnostic material in 71% of cases and cannot reliably distinguish between benign inflammatory processes and malignancy. 1

Immediate Diagnostic Steps

Assess Biopsy Adequacy and Context

• Review the pathology report for specific details: Document the percentage of necrosis, presence of viable tumor cells, stromal components (fibrosis and inflammation), and whether immunohistochemical stains were performed 2
• Determine if neuroendocrine markers were assessed: Chromogranin A, synaptophysin, CD56/NCAM, and Ki-67 labeling index should be evaluated, as atypical carcinoids characteristically show necrosis and cannot be reliably distinguished from typical carcinoids on small biopsies 2
• Check if the sample contained only necrotic material: False-negative results occur when biopsies sample only the necrotic center of malignant masses rather than the viable peripheral tumor 1, 3

Recognize Common Pitfalls

Critical caveat: Atypical cells in lung biopsies are malignant in 73% of cases, but benign conditions including chronic inflammation, tuberculosis, and pneumonia can also produce cellular atypia 4. The presence of necrosis with atypia does not automatically indicate malignancy and requires definitive tissue diagnosis 3.

• Necrosis in biopsy samples reduces diagnostic accuracy 5.2-fold compared to samples without necrosis 3
• Poorly differentiated tumors are misclassified 2.7 times more often than well-differentiated carcinomas when necrosis is present 3
• Lung cancer samples average only 33% tumor cell content, with the remainder being stroma, inflammation, fibrosis, and normal structures 5

Repeat Biopsy Strategy

Imaging-Guided Approach

Obtain ultrasound or CT imaging before repeat biopsy to identify necrotic centers and guide needle placement to viable tumor tissue in the peripheral rim 1:

• For masses with visible necrotic centers on ultrasound: Target the tumor wall rather than the central necrotic area, which improves diagnostic yield to 100% versus 29% when sampling necrotic centers 1
• Use coaxial technique with 18-20 gauge needles: Obtain at least 2 core samples, with 3-6 cores recommended when safely possible to maximize tissue for histological and molecular testing 6
• Target solid-appearing lesions preferentially: Solid lesions have 7.93 times higher odds of yielding malignant diagnosis compared to other appearances 4

Technical Considerations

• Ensure probe position is within rather than adjacent to the lesion: This increases odds of malignant diagnosis 3.36-fold 4
• Obtain samples from multiple sites if the lesion is large (>2 cm): Larger lesions are more likely to yield specific diagnoses than lesions <1 cm 7
• Request immediate adequacy assessment: Diagnostic yield should exceed 90% for lesions >15mm 6

Multidisciplinary Review

Present the case at a multidisciplinary meeting with respiratory physicians, radiologists, thoracic surgeons, and pathologists before proceeding 2:

• Have an expert pathologist review the original biopsy: Problem cases benefit from expert pathology review, particularly when distinguishing neuroendocrine tumors (typical vs. atypical carcinoids) from high-grade neuroendocrine carcinomas 2
• Correlate with clinical presentation: Assess for symptoms (hemoptysis, cough, recurrent infection), smoking history, age, and presence of carcinoid syndrome or Cushing's syndrome from ectopic ACTH 2
• Review all imaging studies: Include chest CT, PET-CT if available (97% sensitivity for nodules ≥1 cm), and prior imaging to assess growth patterns 8

Specific Diagnostic Considerations

If Neuroendocrine Tumor is Suspected

• Ki-67 labeling index is useful for distinguishing carcinoids from small cell lung cancer in small biopsies (Ki-67 >20% suggests high-grade neuroendocrine carcinoma), but cannot reliably separate typical from atypical carcinoids 2
• Mitotic count and necrosis are classification criteria: Atypical carcinoids show 2-10 mitoses per 10 high-power fields and focal necrosis, while typical carcinoids have <2 mitoses and no necrosis—but these distinctions require surgical specimens, not small biopsies 2
• Order somatostatin receptor scintigraphy: 80% of typical bronchial carcinoids express somatostatin receptors 2

If Non-Small Cell Lung Cancer is Suspected

• Do not assign staging based on assumption of malignancy without definitive tissue diagnosis, as the majority of additional small nodules (<8mm) are benign 2
• Request TTF1 staining: Positive TTF1 suggests lung or thyroid origin in metastatic presentations 2
• Ensure adequate tissue for molecular testing: Modern lung cancer management requires identification of targetable mutations (EGFR, ALK, ROS1, PD-L1) 5

Management Algorithm

1. Within 48 hours: Arrange multidisciplinary review of pathology, imaging, and clinical presentation 2

2. Within 1 week:

   • Order PET-CT if not already performed 8
   • Schedule imaging-guided repeat biopsy targeting viable tumor tissue 1
   • Request specific immunohistochemical stains on original specimen if not performed (neuroendocrine markers, Ki-67, TTF1) 2

3. At repeat biopsy:

   • Use ultrasound or CT guidance to avoid necrotic centers 1
   • Obtain 3-6 core samples with coaxial technique 6
   • Request immediate adequacy assessment 6
   • Submit tissue for both histology and molecular testing 6

4. After definitive diagnosis:

   • If malignant: Refer to oncology for systemic therapy or thoracic surgery for resection based on stage 8
   • If benign with specific diagnosis (infection, inflammation): Treat underlying condition
   • If still nondiagnostic: Consider surgical biopsy or close radiographic surveillance based on clinical suspicion 2

Post-Biopsy Monitoring

• Obtain erect chest radiograph 1 hour after biopsy to detect pneumothorax (occurs in 26-54% of core biopsies, requires chest tube in 3.3-15%) 6
• Counsel patients about delayed pneumothorax risk and advise against air travel for 6 weeks 2, 6