Pulmonary, pleural, soft-tissue and bone pathology
Conserve and characterize lung material
A limited lung biopsy or aspirate must provide a reliable diagnosis while preserving material for relevant additional testing. TTF-1, p40 and other markers are selected for a real differential rather than ordered as an indiscriminate large panel. A compatible pattern can support adenocarcinoma, squamous differentiation or neuroendocrine disease, but no stain is positive in every tumor of its broad class. Sampling limits matter: a small focus with lepidic growth does not independently prove that the entire tumor lacks invasion. Resection-based categories require the applicable size, sampling and invasion criteria.
Grade and classify with the relevant framework
Lung adenocarcinoma pattern percentages, high-grade components and the named grading system affect interpretation. A minority high-grade component can matter even when acinar architecture predominates. Small-cell carcinoma combines characteristic cytology with proliferation and appropriate lineage assessment; Ki-67 alone does not distinguish every small blue-cell differential. An actionable fusion or mutation contributes to treatment selection only after the actual assay and clinical context are considered. A reliable predictive result and a complete histological classification are related but different deliverables.
Pleura, inflammation and organisms
Mesothelial lineage markers do not prove malignancy, because reactive mesothelial cells can share them. A suspected malignant mesothelial proliferation needs appropriate morphological, clinical and ancillary assessment. BAP1 loss or a relevant deletion can contribute in the right lineage context, not identify every primary site alone. Noncaseating granulomas and negative organism stains do not independently establish sarcoidosis or exclude all infection. Fungal morphology can suggest a group, while species-level confirmation and the actual host context can remain necessary. Hemosiderin-laden macrophages support prior alveolar bleeding but are not a complete explanation of its cause.
Matrix and molecular evidence in mesenchymal disease
Soft-tissue and bone assessment integrates location, age, imaging, matrix, growth pattern and cell features. Malignant osteoid supports osteosarcoma in the appropriate context; reactive bone production and other tumors must be distinguished. MDM2 amplification contributes to certain lipomatous differentials rather than proving every pleomorphic sarcoma is the same entity. An osteoclast-rich lesion requires the actual mononuclear component and anatomical setting. Molecular tests supplement a coherent diagnosis and do not erase an incompatible pattern. Report sampling limitations and clinically relevant uncertainty rather than overstate what a single core or isolated positive marker can prove.