Article

A Reevaluation of the Clinical Significance of Histological Subtyping of Non-Small-Cell Lung Carcinoma: Diagnostic Algorithms in the Era of Personalized Treatments

Division of Pathologic Anatomy, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy.
International Journal of Surgical Pathology (Impact Factor: 0.96). 08/2009; 17(3):206-18. DOI: 10.1177/1066896909336178
Source: PubMed

ABSTRACT The classification of lung cancer has always been primarily based on the morphologic assessment of routinely stained histological sections, but this approach may be difficult or even unfeasible in cytological preparations or small biopsies. Moreover, the simplistic dichotomization between small-cell carcinoma and non-small cell carcinoma (NSCLC) should be overcome, as new drugs have been discovered that are effective in specific subtypes of lung cancer. A more accurate characterization of NSCLC, however, may be hard in carcinomas lacking clear-cut signs of differentiation. The incorporation into the diagnostic algorithm of poorly differentiated carcinomas of an immunohistochemical panel including markers of squamous (high-molecular-weight cytokeratins, p63) and glandular (TTF-1, cytokeratin 7) cell differentiation seems the most promising approach. The evaluation of lung cancer for gene mutations, gene amplification, tumor-related angiogenesis, expression levels of DNA repair genes and genomic or proteomic profiles represents an exciting challenge for the pathologist in the near future.

2 Followers
 · 
225 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: The vast majority of non-small-cell lung cancers (NSCLCs) presents as advanced disease, and histological diagnosis is widely based on small samples. The differential activity and toxicity profile of new cytotoxic and molecular-targeted therapies according to histotypes requires a precise subtyping of NSCLC. Immunohistochemistry (IHC) contributes to define the most probable histotype; however, the real impact of IHC characterization of NSCLC-not otherwise specified (NOS) in terms of outcome is not well established. A large series of 224 advanced "nonsquamous" NSCLC diagnosed on small biopsy or cytological samples and homogeneously treated was retrospectively selected, all having adequate follow-up data available. Reviewed diagnoses resulted into two groups: adenocarcinoma (ADC) and NSCLC-NOS. The latter was further characterized by IHC (TTF-1, Napsin-A, p40, and Desmocollin-3) -identify a possible, most probable differentiation lineage. Sixty-seven percentage of cases were classified as ADC based on morphological examination only ("morphological ADC") and 33% as NSCLC-NOS. IHC profiling of NSCLC-NOS identified 43.2% of cases with an ADC immunophenotype ("NSCLC favor ADC"), 10.8% with a phenotype favoring squamous lineage, and 46% lacking differentiation features. Survival curves confirmed no difference in terms of outcome between the morphological ADC and the NSCLC favor ADC groups, while a significantly poorer outcome was found in the "null" group in terms of best response, progression-free survival or overall survival (OS). Tumors with an IHC profile ADC-like had an OS comparable with that of morphological ADCs. These findings support the use of IHC to optimize lung cancer histological typing and therapy.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 10/2014; 9(10):1540-6. DOI:10.1097/JTO.0000000000000271 · 5.80 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Large cell carcinoma (LCC) is a merely descriptive term indicating a subtype of lung cancer with no specific features of small-cell lung cancer (SCLC), adenocarcinoma (ADC) or squamous cell carcinoma (SQC). This diagnosis is allowed on surgical specimens only, whereas its counterpart in biopsy/cytology samples is non-small-cell lung carcinoma (NSCLC), not otherwise specified (NOS). Although these two terms do not fulfill the same concept, they can be interchangeable synonyms at the clinical level, reflecting, in different ways, the inability to define a specific subtype. Immunohistochemistry (IHC), next generation sequencing (NGS) analysis and, historically, electron microscopy have been unveiling diverse cell differentiation lineages in LCC, resulting in LCC-favor ADC, LCC-favor SQC and LCC-favor large-cell neuroendocrine carcinoma (LCNEC), the latter hopefully to be included into the neuroendocrine tumor (NET) group in the future. Paradoxically, however, the interpretation issues of LCC/NSCLC-NOS are not diminishing, but even increasing albeight an accurate diagnosis is oncologically required and crucial. Also, rare LCC/NSCLC-NOS cases exhibiting null/unclear phenotype, are difficult to classify, and this terminology could be maintained for the sake of classification (basically these tumors are serendipitous ADC, as also confirmed by the lack of p40). In this review article, seven relevant issues to LCC have been addressed by using a question-answer methodology, with final key points discussing major interpretation issues. In conclusion, most LCC/NSCLC-NOS may be eventually re-classified and addressed by exploiting IHC and/or molecular testing to satisfy the criteria of precision medicine (the right drug, to the right patient, at the right time).
    Lung Cancer 01/2015; 87(3). DOI:10.1016/j.lungcan.2015.01.008 · 3.74 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The gastrointestinal tract (GIT) is an unusual site for metastasis. The rate of GIT metastases detected clinically is very low because of unspecific symptoms and signs of GIT involvement, which include general weakness, tiredness, weight loss, unspecific abdominal pain, fatigue, and anemia. We report clinical, endoscopic, and pathological patterns of two patients (malignant melanoma and primary lung tumor) with metastatic lesions in the gastroduodenum. The first case is a 59-year-old man with unspecific symptoms as nausea, vomiting and abdominal pain. He underwent resection of skin melanoma on his back one year before. Upper gastrointestinal endoscopy revealed two melanotic polypoid masses with ulcerations at the tip, one in the stomach and one in the duodenal bulb. Endoscopic biopsy of these polypoid masses and immunohistochemical stains confirmed the diagnosis of metastatic malignant melanoma. The second case is a 73-year-old man with a two-day history of melena and unspecific abdominal pain. Three weeks before, the patient was operated on for the adenocarcinoma of the lung. Endoscopy of the upper gastrointestinal tract revealed irregular polypoid mass with ulcerations at the tip: three of the stomach mucosa, two in the duodenal bulb and more than ten hemorrhagic polypoid masses at the desendent duodenum. Biopsies of these lesions confirmed the diagnosis of metastatic lung adenocarcinoma. In patients with a history of malignant melanoma and lung cancer unspecific symptoms, like abdominal pain, anemia, and gastrointestinal bleeding gastroduodenal metastases should be suspected. The diagnosis requires careful endoscopic examinations of the mucosa for metastatic lesions and biopsy with special immunohistochemical stains.
    Central European Journal of Medicine 12/2014; 9(6). DOI:10.2478/s11536-013-0321-z · 0.21 Impact Factor

Full-text

Download
43 Downloads
Available from
May 31, 2014