Tumor Classification and Staging

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The classification of lung tumors is based on the microscopic appearance of hemotoxylin and eosin stained tumor sections. The World Health Organization (WHO) tumor classification system is the most widely accepted schema for the histologic typing of lung tumors.

1. Epithelial Tumors

1.1 Benign

1.1.1 Papillomas

1.1.1.1 Squamous

1.1.1.1.1 Exophytic

1.1.1.1.2 Inverted

1.1.1.2 Glandular papilloma

1.1.1.3 Mixed squamous cell and glandular papilloma

1.1.2 Adenomas

1.1.2.1 Alveolar adenoma

1.1.2.2 Papillary adenoma

1.1.2.3 Adenomas of salivary gland type

1.1.2.3.1 Mucous gland adenoma

1.1.2.3.2 Pleomorphic adenoma

1.1.2.4 Mucinous cystadenoma

1.2 Preinvasive lesions

1.2.1 Squamous dysplasia/carcinoma in situ

1.2.2 Atypical adenomatous hyperplasia

1.2.3 Diffuse isiopathic pulmonary neuroendocrine cell hyperplasia

1.3 Invasive malignant

1.3.1 Squamous cell carcinoma

Variants:

1.3.1.1 Papillary

1.3.1.2 Clear Cell

1.3.1.3 Small cell

1.3.1.4 Basaloid

1.3.2 Small cell carcinoma

Variant:

1.3.2.1 Combined small cell carcinoma

1.3.3 Adenocarcinoma

1.3.3.1 Acinar

1.3.3.2 Papillary

1.3.3.3 Bronchioloalveolar carcinoma

1.3.3.3.1 Non-mucinous (Clara cell/type II pneumocyte type)

1.3.3.3.2 Mucinous (goblet cell tpe)

1.3.3.3.3 Mixed mucinous and nonmucinous (Clara cell/type II pneumocyte goblet cell type) or indeterminate

1.3.3.4 Solid adenocarcinoma with mucin formation

1.3.3.5 Mixed

1.3.3.6 Variants:

1.3.3.6.1 Well differentiated fetal adenocarcinoma

1.3.3.6.2 Mucinous (“colloid”)

1.3.3.6.3 Mucinous cystadenocarcinoma

1.3.3.6.4 Signet ring, Clear cell

1.3.6.6.5 Clear cell

1.3.4 Large cell carcinoma

Variants:

1.3.4.1 Large cell neuroendocrine carcinoma

1.3.4.1.1 Combined large cell neuroendocrine carcinoma

1.3.4.2 Basaloid carcinoma

1.3.4.3 Lymphoepithelioma-like carcinoma

1.3.4.4 Clear cell carcinoma

1.3.4.5 Large cell carcinoma withh rhabdoid phenotype

1.3.5 Adenosquamous carcinoma

1.3.6 Carcinomas with pleomorphic, sarcomatoid, or sarcomatous elements

1.3.6.1 Carcinomas with spindle and/or giant cells

1.3.6.1.1 Pleomorphic carcinoma

1.3.6.1.2 Spindle cell carcinoma

1.3.6.1.3 Giant cell carcinoma

1.3.6.2 Carcinosarcoma

1.3.6.3 Blastoma (pulmonary blastoma)

1.3.6.4 Others

1.3.7 Carcinoid tumors

1.3.7.1 Typical carcinoid

1.3.7.2 Atypical carcinoid

1.3.8 Carcinomas of salivary gland type

1.3.8.1 Mucoepidermoid carcinoma

1.3.8.2 Adenoid cystic carcinoma

1.3.8.3 Others

1.3.9 Unclassified carcinoma

2. Soft tissue tumors

2.1 Localized fibrous tumor

2.2 Epitheloid hemangioendothelomia

2.3 Pleuropulmonary blastoma

2.4 Chondroma

2.5 Calcifying fibrous pseudotumor of the pleura

2.6 Congenital periobronchial myofibroblastic tumor

2.7 Diffuse pulmonary lymphangiomatosis

2.8 Desmoplastic small round cell tumor

2.9 Other

3. Mesothelial tumors

3.1 Benign

3.1.1 Adenomatoid tumor

3.2 Malignant

3.2.1 Epithelioid mesothelioma

3.2.2 Sarcomatoid mesothelioma

Desmoplastic mesothelioma

3.2.3 Biphasic mesothelioma

3.3 Other

4. Miscellaneous tumors

4.1 Hamartoma

4.2 Sclerosing hemangioma

4.3 Clear cell tumor

4.4 Germ cell neoplasms

4.4.1 Teratoma, mature

4.4.2 Teratoma, immature

4.4.3 Other germ cell tumors

4.5 Thymoma

4.6 Melanoma

4.7 Others

5. Lymphoproliferative diseases

5.1 Lymphoid interstitial pneumonia

5.2 Nodular lymphoid hyperplasia

5.3 Low-grade marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue

5.4 Lymphomatoid granulomatosis

6. Secondary tumors

7. Unclassified tumors

8. Tumor-like lesions

8.1 Tumorlet

8.2 Multiple meningotheloid nodules

8.3 Langerhans’ cell histiocytosis

8.4 Inflammatory pseudotumor (inflammatory myofibroblastic tumor)

8.5 Organizing pneumonia

8.6 Myeloid tumor

8.7 Hyalinizing granuloma

8.8 Lymphangioleiomyomatosis

8.9 Multifocal micronodular pneumocyte hyperplasia

8.10 Endometriosis

8.11 Bronchial inflammatory polyp

8.12 Others

Diagnosis: Squamous carcinoma of the lung. Species: Human Boston reference set number: LW031

The different types of lung carcinoma are characterized by unique histopathologic features, that enable their differential diagnosis. Squamous cell carcinoma is a malignant eptihelial tumor exhibiting features of squamous epithelium including keratinzation, intercellular bridge or both (10). Tumor cells are characterized by eosinophilic or clear cytoplasm and shrunken nuclei. The nuclei are hyperchromatic with coarse chromatin and may have prominent nucleoli (23).

Diagnosis: Small cell carcinoma of the lung. Species: Human Boston reference set number: LW036

Small cell carcinoma is a neuroendocrine tumor. Neuroendocrine cells are nonciliated, cylindrical cells in the basal mucosa that contain electron-dense neurosecretory granules (10). Histologically, small cell carcinomas are characterized by small cells (larger than lymphocytes) with a high nuclear to cytoplasmic ratio. Nuclei exhibit finely granular chromatin, inconspicuous nucleoli and nuclear molding. Tumors often exhibit high mitotic rates.

Diagnosis: Bronchioloalveolar carcinoma of the lung. Species: Human Boston reference set number: LW035

Adenocarcinoma is a glandular epithelial malignancy displaying growth patterns that are either tubular, acinar, papillary or solid with mucin production. They are diverse tumors with varying degrees of differentiation, even within an individual tumor. The tumor cells are large columnar or cuboidal cells with prominent nuclear membranes and nucleoli. Lesions often display fibrous stroma and tumors may be associated with an apical scar (23). The growth patterns of adenocarcinoma result in destruction of the underlying alveolar architecture. Bronchioloalveolar carcinoma (BAC) is a subtype of adenocarcinoma that is quite distinctive in that it is well differentiated, results in minimal architectural destruction, and does not induce a stromal response.

Diagnosis: Large cell carcinoma of the lung. Species: Human Boston reference set number: LW060

Large cell carcinoma is a malignant epithelial tumor whose differential diagnosis is based upon exclusion of other tumor types. It is defined by large cells with abundant cytoplasm, without glands, keratin, intercellular bridges or other characteristic features of squamous cell, small cell or adenocarcinoma. Tumors most typically grow as sheets or nests of large polygonal cells containing large vesicular nuclei with prominent nucleoli. However, there is a wide spectrum of histological characteristics among different large cell carcinomas.

The clinical course of disease varies with the different subtypes of lung carcinoma and often reflects the stage of disease at the time of diagnosis. The currently accepted staging system for lung carcinoma is a TNM-based system where T refers to the size of the primary tumor; N, to the involvement of regional lymph nodes; and M to the presence of distant metastasis. It was proposed by Mountain in 1986 and was revised in 1997 to give the current International Staging System for Lung Cancer (64). Stage grouping is performed based on a patients TNM descriptors in order to combine subsets of patient's classified according to TNM descriptors into categories that have generally similar treatment options and survival expectations (64).

* The uncommon superficial tumor of any size with its invasive component limited to the bronchial wall, which may extend proximal to the main bonchus, is also classified T1

⁼Most pleural effusions associated with lung cancer are due to tumor.  However, there are a few patients in whom multiple cytopathologic examinations of pleural fluid show no tumor.  In these cases, the fluid is nonbloody and is not an exudate.  When these elements and the patient’s disease judgement dictate that the effusion is not related to the tumor, the effusion should be excluded as a staging element and the patient’s disease should be staged T1, T2, or T3.  Pericardial effusion is classified according to the same rules.

^{^}Separate metastatic tumor nodule(s) in the ipsilateral nonprimary-tumor lobe(s) of the lung are also classified M1.

The TNM staging system does not apply well to small cell carcinomas. A two-stage system including limited and extensive disease is favored.

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