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Year : 2012  |  Volume : 8  |  Issue : 3  |  Page : 445-447

Mixed squamous and large-cell carcinoma of the lung: A case study and literature review

1 Department of Pneumonology, Army General Hospital of Athens, Athens, Greece
2 Department of Cytopathology, Army General Hospital of Athens, Athens, Greece

Date of Web Publication17-Nov-2012

Correspondence Address:
Stamatis Katsenos
Department of Pneumonology, Army General Hospital of Athens, 158 Mesogion and Katehaki Avenue, 115 25 Athens
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-1482.103531

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 > Abstract 

Lung tumors with combined histological pattern are seldom seen exhibiting a more aggressive clinicopathological picture than tumors with a single histology. Herein, we present a 58-year-old male with mixed squamous and large-cell lung carcinoma. The patient was initially diagnosed through fluoroscopy-guided transbronchial lung biopsy with large-cell lung carcinoma of the left upper lobe. He received neo-adjuvant chemotherapy and then underwent left upper lobectomy. Postoperative pathological diagnosis was combined squamous and large-cell neuroendocrine carcinoma. Two months after surgery, restaging revealed brain metastatic deposits. Local radiotherapy was promptly applied with relatively good response and the patient is under observation eight months after diagnosis. A brief review of the current literature is also included with special emphasis on the clinicopathologic aspects and prognosis of lung tumors with mixed histology.

Keywords: Combined lung tumor, immunohistochemistry, large-cell neuroendocrine carcinoma, squamous cell carcinoma

How to cite this article:
Katsenos S, Karachaliou I, Archondakis S. Mixed squamous and large-cell carcinoma of the lung: A case study and literature review. J Can Res Ther 2012;8:445-7

How to cite this URL:
Katsenos S, Karachaliou I, Archondakis S. Mixed squamous and large-cell carcinoma of the lung: A case study and literature review. J Can Res Ther [serial online] 2012 [cited 2021 Dec 5];8:445-7. Available from: https://www.cancerjournal.net/text.asp?2012/8/3/445/103531

 > Introduction Top

Lung tumors with a mixed histology pattern represent a very rare entity that might run a more aggressive clinical course than lung tumors with a single histology. [1],[2] Various combinations of histology types have occasionally been described including adenosquamous carcinoma, combined neuroendocrine and biphasic tumors. We report here a well-documented case of a lung tumor containing concurrently components of squamous and large-cell neuroendocrine carcinoma and attempt a review of the recent literature pertaining to this unusual entity.

 > Case Report Top

A 58-year-old male, heavy smoker (45 packs/ year), was admitted to our department presenting continuing intermittent hemoptysis two weeks before his admission. His past medical history included controllable atrial fibrillation with permanent pacemaker implantation and coronary artery bypass grafting.

Chest radiograph on admission showed a solid mass in the left upper lobe. Further imaging evaluation with integrated fluorodeoxyglucose-positron emission tomography (PET) and axial computed tomography (CT) of the thorax revealed a left upper lobe mass measuring 4.6 cm in diameter with high standardized uptake value (SUV:25.6) and associated enlarged ipsilateral hilar lymph node (SUV:20.1) as well as prevascular mediastinal lymph nodal involvement (SUV:7.8). Fiberoptic bronchoscopy was performed and fluoroscopy-guided transbronchial biopsies were positive for large-cell neuroendocrine carcinoma. Additional work-up using abdominal and brain CT and bone scan did not detect any extra-thoracic metastases. Thus, the disease was clinically classified as Stage IIIA (T2aN2M0).

As the tumor was technically resectable with single-zone mediastinal node involvement (minimal N2 disease), platinum-based induction chemotherapy was started to downstage thus facilitating and simplifying the subsequent surgical procedure. Post-induction chemotherapy downstaging was identified by a new PET/CT scan and the patient underwent left upper lobectomy with concurrent hilar and mediastinal lymph node dissection. Pathology showed a mixed primary lung tumor consisting of two histological types. The tumor, to a large extent, was composed of squamous cell carcinoma with some areas of large-cell neuroendocrine carcinoma. Immunohistochemical analysis showed intense immunoreactivity for cytokeratins AE1/3, 5/6 and cytokeratin clone 34bβ12 indicative of the squamous component of the tumor, as well as for vimentin and CD56 that typify the large-cell component [Figure 1] and [Figure 2]. Furthermore, ipsilateral hilar lymph node (station 10) and single mediastinal (subaortic node/station 5) metastasis from the squamous cell carcinoma component was noted on the resected specimen thus representing the disease stage identical to the clinical one.
Figure 1: Photomicrograph of squamous cell carcinoma component. Immunostaining positive for cytokeratin clone 34βE12 in neoplastic cells; magnifi cation × 100

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Figure 2: Histologic section of large-cell neuroendocrine carcinoma component. Staining positive for CD56 neuroendocrine marker; magnifi cation × 400

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Two months after surgical treatment, regular and thorough restaging work-up revealed metastatic deposits in the right hemisphere of the cerebellum and left temporoparietal region though the patient was asymptomatic. Brain radiotherapy was immediately given (3000cGy/12 fractions) yielding partial response. Following a multimodality therapeutic approach, the patient was counseled for clinical re-evaluation at regular intervals.

 > Discussion Top

Primary lung tumors can be categorized into four major histological types including adenocarcinoma, squamous cell, large-cell and small-cell carcinoma. [3] However, lung tumors may present a mixed histologic pattern, and these neoplasms have been referred to with various terms such as combined or mixed tumors. In particular, these tumors are classified into three groups-adenosquamous, combined neuroendocrine and biphasic. [1],[2] Adenosquamous tumors include the presence of both squamous and glandular malignant components. Combined tumors comprise the association of neuroendocrine tumors and non-neuroendocrine lung carcinoma (NNEC); a further distinction includes small-cell lung carcinoma (SCLC) or large-cell neuroendocrine carcinoma (LCNEC)/NNEC and other neuroendocrine tumors (typical or atypical carcinoid)/NNEC. Biphasic tumors contain both epithelial and mesenchymal malignant components. The actual prevalence of lung tumors with a mixed histologic pattern is unknown but it is estimated at approximately 2-5%.

The combination of squamous cell with large-cell neuroendocrine lung carcinoma appears to be rather infrequent as it has hitherto been described in three isolated cases, although the third one refers to a tumor that consisted of large-cell, squamous and small-cell components. [4],[5],[6] Combined LCNEC/NNEC constitutes a unique group of patients to be considered candidates for surgery, in whom the diagnosis of the LCNEC component is frequently made after resection, thus representing an unexpected finding following surgery for bronchogenic carcinoma. This occurred in all patients in the series of Ruffini et al. [1] Nevertheless, our patient was initially diagnosed with LCNEC and postoperatively with squamous cell lung carcinoma.

Based on two unique recently published studies appraising lung tumors with mixed histologic types, one-third of the patients with LCNEC/NNEC were classified at Stage III, and in about 40% of the cases pneumonectomy was preferred to achieve a curative resection. The present case was also clinically and pathologically categorized as Stage IIIA. Despite the lack of available data regarding the management of combined LCNEC/NNEC with N2 involvement, we espoused the current British Thoracic Society guidelines for the treatment of NSCLC suggesting that patients with "non-bulky" single-zone N2 disease should undergo surgery after induction chemotherapy. [7],[8] Higher five-year postoperative survival rates of about 40% have been demonstrated for single mediastinal nodal disease and pure squamous cell lung cancer. [9]

Among combined LCNEC/NNEC, advanced stages and vascular invasion were significantly more evident characteristics than in the single histology group. Ruffini and co-workers reported a 21% three-year survival rate with no five-year survivors in a series of 19 patients whereas in a recent study Kakir and associates found a 25% two-year survival for the combined neuroendocrine tumor group. [1],[2] On the contrary, higher survival rates were observed for the population of resected lung tumors with single histology. It has been demonstrated that the LCNEC component strongly influences outcome, exhibiting poor prognosis. Extrapolating from these data our case runs an aggressive clinical course since brain metastases were detected after bimodality treatment.

In conclusion, lung tumors with mixed histologic pattern occur rarely, and especially, combined LCNEC and squamous cell carcinoma is relatively uncommon since only sporadic reports exist in the literature. Dual histology is not usually known preoperatively and becomes apparent on the resected specimen. The combination of LCNEC/NNEC presents with an aggressive clinical and histologic behavior leading to shorter survival as compared to the single-histology population of resected lung tumors. Notwithstanding the equivocal evidence on the therapeutic approach for this mixed subtype, a multimodality treatment strategy with surgery having a major role should be considered even in patients with locally advanced disease.

 > References Top

1.Ruffini E, Rena O, Oliaro A, Filosso PL, Bongiovanni M, Arslanian A, et al. Lung tumors with mixed histologic pattern. Clinico-pathologic characteristics and prognostic significance. Eur J Cardiothorac Surg 2002;22:701-7.  Back to cited text no. 1
2.Cakir E, Demirag E, Aydin M, Unsal E. Clinicopathologic features and prognostic significance of lung tumors with mixed histologic patterns. Acta Chir Belg 2009;109:489-93.  Back to cited text no. 2
3.Brambilla E, Travis WD, Colby TV, Corrin B, Shimosato Y. The new World Health Organization classification of lung tumours. Eur Respir J 2001;18:1059-68.  Back to cited text no. 3
4.Bessho T, Yokochi K, Sakurai T. Combined large cell neuroendocrine carcinoma. Jpn J Thorac Cardiovasc Surg 2004;52:426-8.  Back to cited text no. 4
5.Masuya D, Gotoh M, Nakashima T, Liu D, Ishikawa S, Yamamoto Y, et al. Combined large cell neuroendocrine carcinoma and squamous cell carcinoma of the lung; report of a case. Kyobu Geka 2006;59:491-5.  Back to cited text no. 5
6.Chetty R. Combined large cell neuroendocrine, small cell and squamous carcinomas of the lung with rhabdoid cells. Pathology 2000;32:209-12.  Back to cited text no. 6
7.Lim E, Baldwin D, Beckles M, Duffy J, Entwisle J, Faivre-Finn C, et al. Guidelines on the radical management of patients with lung cancer: British Thoracic Society and the Society for Cardiothoracic surgery in Great Britain and Ireland. Thorax 2010;65:1-27.  Back to cited text no. 7
8.Bakir M, Fraser S, Routledge T, Scarci M. Is surgery indicated in patients with stage IIIa lung cancer and mediastinal nodal involvement? Interact Cardiovasc Thorac Surg 2011;13:303-10.  Back to cited text no. 8
9.Pfannschmidt J, Muley T, Bülzebruck H, Hoffmann H, Dienemann H. Prognostic assessment after surgical resection for non-small cell lung cancer: Experiences in 2083 patients. Lung Cancer 2007;55:371-7.  Back to cited text no. 9


  [Figure 1], [Figure 2]

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