Evidence-Based Criteria to Help Distinguish Metastatic Breast Cancer From Primary Lung Adenocarcinoma on Thoracic Frozen Section

Abstract

The distinction between primary lung adenocarcinoma and metastatic breast carcinoma in patients with a history of breast cancer is difficult by frozen section (FS) analysis. Our experience with 129 FSs from 121 patients with a pulmonary nodule and a history of breast cancer was reviewed. The pretest odds ratio of primary pulmonary carcinoma/metastatic breast carcinoma was 2.6. The incidence of 12 histopathologic features was assessed in a "training set" composed of 20 FSs, 10 with primary lung adenocarcinoma and 10 with metastatic breast cancer. A differential diagnosis model composed of significant pathologic features that favor the diagnosis of primary lung adenocarcinoma (acini, lepidic growth, nuclear pseudoinclusions, and scar) or metastatic breast carcinoma (comedonecrosis, solid nests, trabecular architecture, and cribriform growth) was identified. The external validity of this model was successfully tested by challenging 19 pathologists and trainees with a test set of 20 unknown FSs, supporting the clinical applicability of the diagnostic model.

Cribriform adenocarcinoma of the lung: clinicopathologic, immunohistochemical, and molecular analysis of 15 cases of a distinctive morphologic subtype of lung adenocarcinoma

“…This is of importance for differential diagnosis as tumors other than colorectal adenocarcinomas demonstrating a prominent cribriform growth pattern are capable of metastasizing to the lung and can arise from diverse sites such as the gallbladder, 33 paranasal sinuses, 34 urinary bladder, 35 breast, 11 prostate, 10 pancreas, 36 salivary glands, 37 thyroid, 38 sweat glands, stomach, ovary, 39 uterus, and endocervix. 40 Adenocarcinomas of the prostate and breast can metastasize to the lung and can often display a cribriform architecture with comedonecrosis.…”

“…9 In primary lung tumors, a pure or predominant cribriform architecture is rare; most tumors displaying this type of architecture have been commonly regarded as metastases, particularly from the prostate, breast, and colon. 3,10,11 Mutations in the epidermal growth factor receptor (EGFR) and the KRAS genes, and rearrangements in the anaplastic lymphoma receptor tyrosine kinase (ALK), the c-ros oncogene 1, receptor tyrosine kinase (ROS1) genes, and the RET proto-oncogene are among the most frequently observed molecular alterations in lung adenocarcinomas. 4,12 ALK, ROS1, and RET gene rearrangements occur exclusively of EGFR or KRAS mutations with rare exception.…”

Second primary lung carcinoma in patients with first primary breast carcinoma: two case reports and review of the literature

“…In histological sections, the existence of acini, lepidic growth, nuclear pseudoinclusions, and scar favor the diagnosis of primary lung adenocarcinoma; on the contrary, comedonecrosis, solid nests, trabecular architecture, and cribriform growth can be identified in metastatic breast carcinoma [18]. Such a distinction can also be achieved by detection of special markers on the histological specimens, such as Thyroid transcription factor-1 (TTF-1) or mammaglobin 1 [19,20].…”

Evidence-Based Principles in Pathology: Existing Problem Areas and the Development of “Quality” Practice Patterns

“…These have been concerned with testing the clinical usefulness (or lack of it) for existing diagnostic nomenclatures and classifications of selected thymic, thyroid, and pulmonary lesions; the selection of optimally performing antibody panels for tumor immunohistochemistry; and the relative values of different predictive and prognostic assays relating to lung carcinomas. [101][102][103][104][105][106][107][108][109][110][111][112] The other of us (M.R.W.) has subsequently introduced the results of those studies into his own practice (and that of his colleagues), with confirmatory results.…”

“…108,109,111,112 Moreover, they can be adopted successfully and without undue effort by virtually all laboratory practitioners.…”