The central type and the peripheral type :

Morphologically, peripheral SCCs are smaller, have fewer mitoses, less prevalent lymphatic invasion, and a more intense stromal reaction. Improved survival in patients with peripheral SCC may be due to a more favorable stage at the time of initial treatment.

According to a study the patient population of the peripheral type was older, with a lower pathologic stage, lower lymphatic vessel involvement, and lymph node metastasis.

 Based on the histologic growth pattern, the peripheral type was classified under three subgroups as follows:

1  the alveolar space-filling type, 2)  the expanding type, and 3)  the combined type.

Among these three types, the alveolar space-filling type showed neither lymphatic vessel invasion nor lymph node metastasis and had the most favorable prognosis.

The central and peripheral types of lung squamous cell carcinoma have different clinicopathologic characteristics and should be classified under respectively different categories.

OBJECTIVE: Although the incidence of peripheral squamous cell carcinomas (SqCCs) of the lung has increased over recent years, histologic prognostic factors for small peripheral SqCCs have not been well established. The aim of this study is to identify clinicopathologic prognostic factors. MATERIALS AND METHODS: We evaluated various clinicopathologic parameters in 101 patients with peripheral lung SqCCs (defined as tumors located in or more peripheral to the fourth branching bronchus), measuring < or = 30 mm in diameter. RESULTS: Multivariate analysis showed that the size of the minimal tumor nest (MTN), a background of usual interstitial pneumonia (UIP) and lymph node metastasis were significant prognostic factors. MTN sizes were defined as large (>6 tumor cells), small (2-5 tumor cells) or single cell. The 5-year disease-free survival rate was significantly worse in patients with single cell nests (50 patients, 69.5%) than in those with small nests (42 patients, 94.1%) (P = 0.0035, log rank test). The MTN size had a significant impact on survival in patients with pathologic stage IA disease and tumors < or = 20 mm in diameter. A background of UIP, which correlated with the presence of a single cell invasive component and pleural involvement, was also a poor prognostic factor, suggesting that peripheral SqCC in UIP is highly malignant even if the tumor is small. CONCLUSION: The MTN size is a useful prognostic factor for small peripheral SqCCs. Tumors with a single cell invasive component appear to be highly malignant, and should be distinguished from invasive cancers with a low malignant potential (tumors with large or small tumor nest components).

Characterization of cell-type specific profiles in tissues and isolated cells from squamous cell carcinomas of the lung.Lung Cancer. 2006 Aug;53(2):129-42. Epub 2006 Jun 6.

Lung cancer accounts for 28% of all cancer deaths, a higher percentage than any other human cancer. Squamous Cell Carcinoma (SqCC) is the most common lung neoplasm and is a tumor that is extensively associated with tobacco use. Despite the association of many genetic alterations with lung cancer, the precise molecular mechanisms of tumorigenesis, for the most part, remain ambiguous. Although many studies of lung cancer have used global transcript profiling approaches designed to uncover genes or pathways that are important in lung tumorigenesis, no strong candidates have emerged. A lack of concurrence amongst these various studies can be attributed, in a large part, to the cellular heterogeneity within lung tissue. We have attempted to reduce this complication by designing a profiling strategy that will minimize the confounding involvement of tissue heterogeneity in gene expression of lung tumors. Specifically, we have profiled transcript expression levels in both isolated cells and tissues from SqCC and normal samples. Our strategy consists of combining and subtracting the input of these various cell types which has produced a unique transcript profile of the squamous carcinoma cell. We then analyzed the data using Pathways Assist analysis software to determine which processes may be involved in SqCC tumorigenesis. The MAP/ERK pathway involved in growth and differentiation was the pathway that was most frequently identified across all comparisons. In addition, biological interaction networks of the SqCC profile identified IL-8 as playing a potentially important role SqCC development.

Clinicopathologic features of peripheral squamous cell carcinoma of the lung. Ann Thorac Surg. 2004 Jul;78(1):222-7.

BACKGROUND: The clinicopathologic features are still unknown in peripheral squamous cell carcinoma of the lung, unlike centrally located carcinomas. In this retrospective study, we investigated the clinicopathologic characteristics of patients with peripheral squamous cell carcinomas. METHODS: Of 1,381 primary lung carcinomas surgically resected at the National Cancer Center Hospital, Tokyo, from 1995 through 2001, 70 (5.1%) peripheral squamous cell carcinomas of 3.0 cm or less in diameter were studied retrospectively in terms of clinicopathologic characteristics such as age, sex, past history, smoking, tumor size, mode of operation, extent of lymph node dissection, pathologic lymph node status, mode of recurrence, and cause of death. RESULTS: These patients ranged in age from 49 to 82 years, with a mean age of 69.2 years. Thirty-nine patients (56%) were at increased risk preoperatively. The incidence of lymph node metastasis was 25%, and larger tumors tended to be associated with a higher prevalence, although this difference was not significant (p = 0.12). None of the patients with N2 disease had skipping metastasis. Recurrence was observed in 13 patients (19%). There was no significant correlation between recurrence and the extent of lymphadenectomy or the mode of operation. The 5-year overall and disease-specific survival rates were 73.4% and 85.9%, respectively. The cause of death was recurrence in 53% and other disease in 47%. CONCLUSIONS: We propose that mediastinal hilar lymphadenectomy should be routinely conducted as a curative operation for low-risk patients with small peripheral squamous cell carcinoma. We further propose that for patients who may have difficulty tolerating this procedure, pathologic examination of intraoperative frozen sections from the hilar node could be useful for planning a surgical strategy.

Cavitating squamous cell lung carcinoma-distinct entity or not? Analysis of radiologic, histologic, and clinical features.Lung Cancer. 2004 Sep;45(3):349-55.

INTRODUCTION: Patients with cavitating squamous lung carcinoma (cSLC) are believed to harbor aggressive, chemoresistant disease with distinct features and fare poorly. We retrospectively analyzed radiologic, histologic, and clinical features of patients with cSLC and solid SLC (sSLC) from the patient registry of four Hellenic Cooperative Oncology Group (HeCOG) cancer centres in an effort to detect distinct characteristics of cSLC. PATIENTS AND METHODS: 37 cSLC and 212 sSLC patients, most of them male smokers, aged more than 60, treated with resection and/or chemotherapy/radiotherapy were included in the analysis. Disease stage, histologic differentiation and lymphatic/vascular invasion, pre-diagnosis symptoms and their duration, tumor size, site and associated features, metastatic sites, chemotherapy administered, responses and duration as well as time to treatment failure, and overall survival were analyzed for significant differences between the two patient groups. RESULTS: Statistically significant differences (two-sided P < 0.05) in patients with cSLC were found for: locally advanced (IIIB) or metastatic (IV) disease (76.5%) at presentation, longer duration of pre-diagnosis symptoms (mean 10 months), more frequent manifestation of fever, cough, weight loss, poor tumor differentiation, lower lobe primary, absence of atelectasis and satellite lesions. Objective response rates (33% for cSLC versus 32% for sSLC) and response duration (median 6 versus 5 months) were no different in the two patient groups. Median time to treatment failure (TTF) and overall survival (OS) were 10 and 13 months for cSLC patients, whereas 12 and 18 months for sSLC patients. Two-year TTF and OS rates were 18.5% and 33.5% for cSLC, while they were 19.3% and 40% for sSLC. No statistically significant differences were observed in any survival curves. CONCLUSION: Patients with cSLC present with high grade tumors that may initially simulate infectious processes, leading to late diagnosis despite long standing symptoms and presentation with advanced disease. In view of lack of evidence for differential disease course, increased chemoresistance and inferior outcome in comparison to sSLC patients, the definition of cavitating pulmonary carcinoma as a distinct clinical subentity cannot be supported.

The clinicopathological features of peripheral small-sized (2 cm or less) squamous cell carcinoma of the lung. Kyobu Geka. 2004 Jan;57(1):56-60.

Recently the diagnosis of peripheral small-sized lung cancers has increased with the development of computed tomography. The vast majority of them are adenocarcinoma, whereas squamous cell carcinoma is rare. From 1981 to 2002, 1,054 patients underwent pulmonary resection for primary lung cancer in National Nishigunma Hospital. Among of them, 17 patients with peripheral small-sized (2 cm or less) squamous cell carcinoma underwent lobectomy and systemic nodal dissection were retrospectively reviewed. These were 15 men and 2 women, with a mean age of 68 years (range, 56-75). Regarding the pathologic stage, 15 patients were classified in stage IA, 1 in IIA, and 1 in IIIA. Among of them, only 1 patient with n 2 disease died of cancer at 17 months after surgery. Overall 5-year and 10-year survival rates of this disease were 84.4% and 73.8%, respectively. Based on the present data, we conclude that mediastinal nodal dissection would be unnecessary in the patients with peripheral small-sized squamous cell carcinoma of the lung.

Clinicopathologic characteristics of peripheral squamous cell carcinoma of the lung. Am J Surg Pathol. 2003 Jul;27(7):978-84.

Squamous cell carcinoma of the lung can be divided into two types according to the location of the primary site: the central type and the peripheral type. The clinicopathologic factors in the peripheral type of lung squamous cell carcinoma have not yet been fully evaluated. A total of 204 surgically resected lung squamous cell carcinomas were reviewed with special reference to their location, histologic characteristics based on tumor growth patterns, and clinicopathologic factors. The central type and the peripheral type accounted for 95 and 109 cases, respectively. Although the patient population of the peripheral type was older, with a lower pathologic stage, lower lymphatic vessel involvement, and lymph node metastasis, the Kaplan-Meier survival proportions did not differ significantly between these two groups. Based on the histologic growth pattern, the peripheral type was classified under three subgroups as follows: 1). the alveolar space-filling type, 2). the expanding type, and 3). the combined type. Among these three types, the alveolar space-filling type showed neither lymphatic vessel invasion nor lymph node metastasis and had the most favorable prognosis. The central and peripheral types of lung squamous cell carcinoma have different clinicopathologic characteristics and should be classified under respectively different categories.

Prognostic comparison between peripheral and central types of squamous cell carcinoma of the lung in patients undergoing surgical resection.Oncol Rep. 2000 Mar-Apr;7(2):319-22.

In order to define whether the location of the tumor [peripheral (P) or central (C)] may have some influence on the prognosis for patients with squamous cell carcinoma of the lung, we analyzed 235 patients under 80 years of age (P-group = 129, C-group = 106) who had undergone surgical resection between January 1985 and December 1997. There was no significant difference in the prognosis between the two groups with stages I(0)-IIIB of the disease. We concluded that as a whole the location of the tumor may not have significant influence on the prognosis in patients with squamous cell carcinoma of the lung undergoing surgical resection.

Comparison of endoscopic features of early-stage squamous cell lung cancer and histological findings.Br J Cancer. 1999 Jul;80(9):1435-9.

Seventy cases with early-stage central-type squamous cell carcinoma were treated surgically between 1984 and 1993 in seven participating institutes. We classified endoscopic features of early-stage central-type squamous cell carcinoma into three types (hypertrophic type, nodular type and polypoid type). After surgery we investigated the relationship between endoscopic features and both the area of superficial extent and depth of carcinoma invasion based on histopathological investigations of the surgical specimens. In 66.7% of the hypertrophic type lesions cancer cells did not invade into the cartilaginous layer, and only 4.8% of this type showed tumour invasion beyond the bronchial cartilage. On the other hand, a few nodular and polypoid type cases showed in-situ carcinoma or carcinoma with invasion from the subepithelial layer to the muscle layer, and in approximately 20% the these types we observed carcinoma invasion beyond the cartilaginous layer, which was not suitable for photodynamic therapy. Also, concerning the greatest dimension 24 out of 35 lesions (68.6%) less than 10 mm in the greatest dimension were evaluated as either in-situ carcinoma or micro-invasive tumour within the muscle layer. The endoscopic features can provide a basis for the determination of therapeutic strategy in early-stage central-type lung cancer.

Outcome of patients with early stage lung cancer. Surg Today. 1998;28(7) : 736-9.

A study was conducted to evaluate the outcomes of 79 patients with early stage lung cancer diagnosed according to the following criteria. Central tumors were located in the segmental bronchi, or more proximally, and tumor invasion was limited to the bronchial wall without lymph node or distant metastases. Peripheral tumors were located distal to the subsegmental bronchi and were less than 2 cm in greatest dimension, and invasion was limited to the visceral pleura, with no lymph node or distant metastases. The 5-year survival rate was 100% for patients with peripheral type early squamous cell carcinoma, 94.6% for those with central-type early squamous cell carcinoma, and 79.3% for those with early adenocarcinoma. The 5-year survival rate for patients with central-type squamous cell carcinoma without pericartilage layer invasion was 97.0%, and that for those with T1N0M0 peripheral squamous cell carcinoma was 100.0%. To define early stage lung cancer as curable, it should be defined as T1N0M0, peripheral squamous cell carcinoma, or central squamous cell carcinoma without pericartilage layer invasion. For other histologic types, some added parameters are needed. The rate of multiple lung cancers was 10.1% and that of multiple primary malignant disease was 13.9%. Thus, careful followup of patients with early stage lung cancer should be carried out, as second malignancies in the lung and elsewhere are commonly detected.

Squamous cell carcinoma antigen as an adjunct tumour marker in primary carcinoma of the lung.  J Clin Pathol. 1994 Jun;47(6):535-7.

AIMS--To determine (1) the detection rate of primary carcinoma of the lung by serological assay of CEA (carcinoembryonic antigen); and (2) whether addition of seroassay of squamous cell carcinoma related antigen before treatment improves detection sensitivity. METHODS--A prospective study spanning 27 months was conducted at the University Hospital, Kuala Lumpur. Serum CEA (Abbott IMx) and serum squamous cell carcinoma antigen (Abbott IMx) from patients clinically suspected of having primary carcinoma of the lung, were assayed using the microparticle enzyme immunoassay method. RESULTS--Thirty seven cases of histologically confirmed primary lung carcinoma were studied. Of these, 17 were squamous cell carcinomas, 10 adenocarcinomas, nine small cell carcinomas, and one large cell carcinoma. The patients' ages ranged from 34-82 years. The male:female ratio was 3.6:1. Squamous cell carcinoma antigen was raised above the cutoff value of 1.5 ng/ml in 94.1% of squamous cell carcinomas, 20.0% of adenocarcinomas, and 11.1% of small cell carcinomas. By comparison, CEA was raised above the cutoff value of 3.0 ng/ml in 70.6% of squamous cell carcinomas, 77.8% of small cell carcinomas, and 100% of adenocarcinomas. CEA and squamous cell carcinoma antigen were not raised in the patient with large cell carcinoma and in 14 healthy volunteers. None of 15 patients with a variety of benign lung diseases showed a rise of CEA, while two patients--a 25 year old Indian woman with pneumonia and a 64 year old Malay man with bronchial asthma--had raised squamous cell carcinoma antigen values above the cutoff. Serum CEA and squamous cell carcinoma antigen values did not seem to correlate with stage or degree of differentiation of the tumours. CONCLUSIONS--The findings suggest that CEA is a good general marker for carcinoma, particularly adenocarcinoma. In contrast, squamous cell carcinoma antigen is more specific for squamous carcinoma.

Pseudovascular adenoid squamous cell carcinoma of the lung: clinicopathologic study of three cases and comparison with true pleuropulmonary angiosarcoma.Hum Pathol. 1994 Apr;25(4):373-8.

Pseudovascular adenoid squamous cell carcinoma (PASCC) is a variant epithelial neoplasm with the ability to simulate the growth pattern of angiosarcoma. It has been documented in the breast, skin, and, recently, lung. We describe three additional examples of pulmonary PASCC occurring in two men and one woman. The patients' ages ranged from 47 to 54 years at diagnosis, and all patients had radiographically and macroscopically typical squamous carcinomas of the lung. Histologically, the tumors showed the presence of interanastomosing pseudoluminal spaces that were lined by obviously atypical epithelioid cells and focally contained erythrocytes. Overtly carcinomatous growth was apparent only very focally. A comparison case of true pleuropulmonary angiosarcoma in a 57-year-old man showed closely similar microscopic features, but it lacked areas that resembled conventional carcinomas. Immunohistologic studies revealed uniform reactivity for keratin in PASCC of the lung. Two cases also stained positively for epithelial membrane antigen and vimentin, but all of them were negative for von Willebrand factor, CD31, CD34, and binding of Ulex europaeus I lectin. Electron microscopic examination of the three cases showed the presence of intercellular desmosomes and cytoplasmic tonofibrils. The example of true pleuropulmonary angiosarcoma demonstrated an endothelial immunophenotype. Two of three patients with pulmonary PASCC survived for at least 20 months, whereas the individual with true angiosarcoma died within 3 months. Together with prior reports on such lesions, these data suggest that angiosarcoma-like carcinomas of the lung differ pathologically and behaviorally from primary pulmonary endothelial malignancies.

Early squamous lung cancer and longer survival rates. Respiration. 1993;60(6):359-65.

The criteria for early squamous lung cancer remain open to discussion as patients who have been treated for early stage lung cancer, such as T1N0M0, and appear to have been cured clinically may die from recurrent or metastatic tumors. We reviewed the pathological data on 242 surgical patients with squamous lung cancer and found 31 cases (13%) of early lung cancer, included were early lung cancer of the hilar type as a lesion restricted to the bronchial wall without lymph node involvement, and early lung cancer of the peripheral type as a lesion of less than 2 cm and surrounded by visceral pleura but without lymph node involvement. Of 89 patients with hilar-type squamous lung cancer, 17 (19%) had early lung cancer, and 14 (9%) of 153 patients with peripheral-type squamous lung cancer had early lung cancer (p < 0.05). For early lung cancer of the hilar type, all but 1 (94%) were detected using sputum cytologic study and bronchoscopy. For early lung cancer of the peripheral type, all were detected on chest X-ray, but 57% were cytologically proven to be malignant. The 5-year survival rate for patients with early lung cancer, according to this new criteria is 90%; 92% for the hilar type and 88% for the peripheral type. Thus, classification of early squamous lung cancer is pertinent for determining the prognosis and selection of treatment. We emphasize that efforts be made to detect early lung cancer.

Peripheral vs central squamous cell carcinoma of the lung. A comparison of clinical features, histopathology, and survival.Arch Pathol Lab Med. 1990 May;114(5):468-74.

We reviewed the clinical features and histopathologic findings of 21 peripheral pulmonary squamous cell carcinomas (SCC) resected at our institution between 1961 and 1981 and compared them with 19 central SCCs. Histologic features were scored semiquantitatively from 0 to 3+. Peripheral SCC represented 16% of all resected SCCs. The proportion of patients with multiple symptoms was lower and survival during the 5 years after surgery was better in the peripheral group. Tumor size, mitoses per high-power field (2.4 +/- 0.3 vs 4.1 +/- 0.6 [SEM]), prevalence of lymphatic invasion (19% vs 58%), and lymph node metastases (5% vs 37%) were lower, while chest wall invasion was more frequent (25% vs 0) for peripheral SCCs. Peripheral tumors also had more intense (2 or 3+) lymphoplasmacytic (86% vs 47%) and desmoplastic (95% vs 68%) reactions. Cox regression analysis did not support a significant relationship between tumor location and survival. We conclude that, compared with the central SCC, peripheral SCC is associated with fewer symptoms at presentation and better survival. Morphologically, peripheral SCCs are smaller, have fewer mitoses, less prevalent lymphatic invasion, and a more intense stromal reaction. Improved survival in patients with peripheral SCC may be due to a more favorable stage at the time of initial treatment.