Toward personalized medicine of lung cancer: response to nontargeted therapy in invasive pulmonary adenocarcinoma as a function of tumor cell differentiation.

We evaluated clinical parameters, histomorphology, and thyroid transcription factor 1 (TTF-1) immunoreactivity in 40 epidermal growth factor receptor (EGFR) mutation- and anaplastic lymphoma kinase (ALK) rearrangement-negative invasive pulmonary adenocarcinomas. Tumors were histomorphologically quantitated by a pulmonary pathologist and TTF-1 immunohistochemistry applied. EGFR mutation and ALK rearrangement status was determined with polymerase chain reaction/DNA sequencing and fluorescence in situ hybridization, respectively. Treatment response was related to type of treatment (P < .005) and clinical stage (P = .001). EGFR mutation- and ALK rearrangement-negative pulmonary adenocarcinomas containing papillary/micropapillary histology showed greater morphologic heterogeneity (P < .001), greater TTF-1 immunoreactivity (P = .004), and were more common in treatment responders (P < .05). These findings support that patients with pulmonary adenocarcinomas that are subject to nontargeted therapies may respond to treatment as a function of tumor cell differentiation with TTF-1 as a potential biomarker of this response.

Primary malignant fibrous histiocytoma (myxofibrosarcoma/pleomorphic sarcoma not otherwise specified) of the breast: clinicopathologic study of 19 cases.

We present 19 cases of primary breast malignant fibrous histiocytoma (MFH) or myxofibrosarcoma/pleomorphic sarcoma not otherwise specified, the largest series to date, and compare our results with those in the literature to better define MFH in this anatomical location. Twenty-seven cases (MFH, myxofibrosarcoma, or pleomorphic sarcoma not otherwise specified) were reviewed using World Health Organization and French Federation of Cancer Centers criteria. Inclusion required location within breast parenchyma without extensive chest wall involvement. Morphological features were recorded, and immunohistochemistry was applied. Clinical data were extracted from patients' medical records. Clinically, there was 1 male patient. Of 15 patients with follow-up, 5 (33% overall) died of disease within an average of 7 months after diagnosis. Distant metastases and older patient age were associated with poor survival. Storiform-pleomorphic subtype was most common (10/19) with myxofibrosarcoma (6/19) and giant cell subtype (1/19) also observed. Unique lymphocyte-rich (1/19) and pleomorphic hyalinizing angiectatic tumor-like (1/19) morphologies are presented. Immunohistochemistry demonstrated expression of CD68 (71%), focal smooth muscle actin (36%), with rare focal estrogen and progesterone receptor immunoreactivity. All cases were negative for CD34, S-100 protein, desmin 33, and keratins, including CK7, CK20, CK5/6, and CK18. Malignant fibrous histiocytoma occurs as a primary lesion in breast parenchyma. Attention to morphological detail and immunohistochemistry avoids misdiagnosis. Entrapped breast ductal epithelium should not be misinterpreted as the epithelial component of a biphasic tumor. A florid lymphoid response should not be confused with metaplastic carcinoma. Pleomorphic hyalinizing angiectatic tumor-like features may be observed in MFH. Our study confirms the presence of MFH in breast and presents unique morphological observations of primary breast MFH.

Del(5q) is associated with clinical and histological parameters in small cell neuroendocrine lung carcinoma.

To elucidate the relationship between del(5q) and the clinical and histological features of small cell neuroendocrine lung carcinoma, 33 tissue samples from patients with this tumor were evaluated. By using fluorescence in situ hybridization, del(5q) was identified in almost 50% of cases (15/33, 45%). Clinically, patients with tumors showing del(5q) were older (mean age = 71 years) with a correspondingly greater pack-year smoking history (mean = 61) than patients with tumors (mean age = 59 years, mean pack-years = 44) without del(5q). Histologically, tumors with del(5q) had a greater frequency of spindle cell morphology (11/14 [79%] vs 6/16 [38%], P < .025) than those without del(5q). This is the first study to find an association between del(5q) and tumor histology in small cell neuroendocrine lung carcinoma.