A report of six cases
Adnan YILMAZ1, Ebru SULU1, Sibel ARINÇ1, Cüneyt SALTÜRK1, Erdal OKUR2, Ferda AKSOY3, Semih HALEZEROĞLU2
1Süreyyapaşa Göğüs ve Kalp Damar Hastalıkları Eğitim ve Araştırma Hastanesi, Göğüs Hastalıkları Kliniği,
2Süreyyapaşa Göğüs ve Kalp Damar Hastalıkları Eğitim ve Araştırma Hastanesi, Göğüs Cerrahisi Kliniği,
3Süreyyapaşa Göğüs ve Kalp Damar Hastalıkları Eğitim ve Araştırma Hastanesi, Patoloji, İstanbul.
ÖZET
Akciğerin pleomorfik karsinomu: Altı olgunun sunumu
Pleomorfik akciğer karsinomlu altı olguyu sunduk. Olguların dördü erkek, ikisi kadın olup yaşları 43-64 (ortalama yaş 54.3) yıl arasında değişiyordu. İki olgu sigara içmezken, dört olgu sigara içiyordu ve ortalama sigara kullanım 52.5 (30-90) pa- ket-yıl idi. Bronkoskopik inceleme ile üç olguda endobronşiyal lezyon saptandı. Pleomorfik karsinom tanısı bir olguda ke- sici iğne biyopsisi, beş olguda ise torakotomi ile elde edildi. Epitelyal tümör komponenti üç olguda epidermoid, üç olguda adenokarsinom idi. Bir olguda kemik metastazı vardı. Kemoterapi alan hasta iki ay yaşadı. Cerrahi uygulanan beş hasta- da patolojik evre iki olguda IB, iki olguda IIB ve bir olguda IV idi. Tedavi yöntemi üç olguda lobektomi, iki olguda pnömo- nektomi idi. Cerrahi sonrası sağkalım süresi 2-20 ay arasında değişiyordu. Sonuç olarak, pleomorfik karsinom akciğerin nadir tümörüdür. Tanı sıklıkla torakotomi ile elde edilir. Bu tümörler kötü prognoza sahiptir.
Anahtar Kelimeler: Pleomorfik karsinom, akciğer, tanı, tedavi, prognoz.
SUMMARY
Pleomorphic carcinoma of the lung: A report of six cases
Adnan YILMAZ1, Ebru SULU1, Sibel ARINÇ1, Cüneyt SALTÜRK1, Erdal OKUR2, Ferda AKSOY3, Semih HALEZEROĞLU2
1Department of Chest Diseases, Süreyyapaşa Thoracic and Cardiovascular Diseases Training and Research Hospital, İstanbul, Turkey,
2Department of Chest Surgery, Süreyyapaşa Thoracic and Cardiovascular Diseases Training and Research Hospital, İstanul Turkey,
3Department of Pathology, Süreyyapaşa Thoracic and Cardiovascular Diseases Training and Research Hospital, İstanbul, Turkey.
Yazışma Adresi (Address for Correspondence):
Dr. Adnan YILMAZ, Altayçeşme Mahallesi Seri Sokak Yaşamkent Sitesi C-Manolya Blok No: 11 Daire: 26 Maltepe, İSTANBUL - TURKEY
e-mail: adnandr_63@yahoo.co.uk
Pleomorphic carcinoma was recently classified as a subgroup of the general category of carci- nomas with pleomorphic, sarcomatoid, or sar- comatous elements. Histologically, a pleomorp- hic carcinoma is defined as either a non-small cell lung carcinoma combined with neoplastic spindle and/or giant cells or a carcinoma that consists of only spindle and giant cells. Ple- omorphic component should comprise at least 10% of the neoplasm (1). Pleomorphic carcino- ma, quoted by Chang and associates, is prima- rily found in the oral cavity, larynx, breast, kid- ney, urinary bladder, uterus and conjunctiva (2).
It is considered to be a rare tumor of the lung, which accounts for only 0.3% of all lung malig- nancies (3). The rarity of pleomorphic carcino- mas and their histologic similarity to other neop- lasms, result in difficult diagnosis (2). It was re- ported that these tumors invade mediastinal structures, pleura and chest wall, and show signs of early distant metastases (2,4,5). Its prognosis is poor, with a median survival time of only 10 months (3). We presented six patients with pleomorphic carcinoma of the lung.
MATERIALS and METHODS
Between 2001 and 2005, we retrospectively re- viewed the records of pathology department. We identified six patients with pleomorphic carcino- ma of the lung during that period. Pathologic preparations of all patients were reexamined by the same pathologist. Hematoxylin and eosin- stained sections were present in all cases. Im- munohistochemical staining for keratin, epitheli- al membrane antigen (EMA) and vimentin was performed in three cases. The diagnosis of pul-
monary pleomorphic carcinoma was based on the criteria set by the World Health Organization (6). The medical records of the patients were analyzed retrospectively. Records were reviewed for the following: age, sex, symptoms, history of smoking, radiological features, diagnostic met- hods, pathologic findings, stage of the tumor, and treatment. Follow-up information for pati- ents was obtained from direct patient or family contact on January 2006.
RESULTS
The present study included six patients. Four pa- tients were male and two patients were female.
Their ages ranged from 43 to 64 years, with a mean age of 54.3 years. While two patients were nonsmoker, four patients were current smoker, with a mean smoking history of 52.5 (30-90) pack-years. The most frequent symptom was chest pain. This data was shown in Table 1.
Chest X-ray demonstrated mass lesion in all pa- tients. Mass was located on right middle zone in two cases, on left lower zone in one case, on left upper and middle zone in one case, on right up- per zone in one case, and on left upper zone in one case. Table 2 summarizes computed tomog- raphy (CT) and bronchoscopy findings. Tumor was located in upper lobes in four cases and in lower lobes in two cases. On bronchoscopic exa- mination, the tumor was located peripherally in four cases and centrally in two cases. Pathologic diagnosis of bronchoscopic biopsies was non- small cell carcinoma in one case and squamous cell carcinoma in one case. Bronchoscopic biop- sies were not diagnostic in remaining 4 cases.
We presented six patients with pleomorphic carcinoma of the lung. There were 4 male and 2 female whose ages ranged from 43 to 64 years, with a mean age of 54.3 years. While two patients were nonsmoker, four patients were current smo- ker, with a mean smoking history of 52.5 (30-90) pack-years. Bronchoscopic examination detected endobronchial lesion in three patients. The diagnosis of pleomorphic carcinoma was established with cutting needle biopsy in one case and with thoracotomy in five cases. Epithelial component was squamous cell carcinoma in three cases and adenocarcinoma in the other three cases. There was bone metastasis in one case. She received chemotherapy and died two months after therapy.
Among five patients who underwent surgery, pathologic staging was Stage IB in two patients, Stage IIB in two patients and Stage IV in one patient. Treatment modality was lobectomy in three cases and pneumonectomy in two cases. Survival time for patients after surgery was 2 to 20 months. In conclusion, pleomorphic carcinoma is a rare tumor of the lung. Diag- nosis is frequently established with thoracotomy. These tumors have poor prognosis.
Key Words: Pleomorphic carcinoma, pulmonary, diagnosis, treatment, prognosis.
The pathologic diagnosis of pleomorphic carci- noma was made with cutting needle biopsy in one case (case 4). Pathologic diagnosis was made at thoracotomy in five patients. Immuno- histochemical staining was performed in three cases. Epithelial cells were stained with keratin and EMA, but not with vimentin. Spindle cells were stained with vimentin, but not with keratin and EMA. Epithelial component was squamous cell carcinoma in three cases and adenocarcino- ma in the other three cases (Figure 1). There was bone metastasis in one case. She received chemotherapy and died two months after the- rapy. Treatment modality was lobectomy in three cases and pneumonectomy in two cases.
Among five patients who underwent surgery, pathologic staging was Stage IB in two patients, Stage IIB in two patients and Stage IV in one pa- tient. Survival time for four patients after diagno- sis was between 2 and 20 months. Clinical data including diagnosis, pathology, stage and treat- ment on six patients of pleomorphic carcinoma were represented in Table 3.
DISCUSSION
Pleomorphic carcinoma is an infrequent tumor of the lung (2,3). It is defined as “a poorly diffe- rentiated non-small cell lung carcinoma, namely squamous cell carcinoma, adenocarcinoma or large cell carcinoma, containing spindle cells and/or giant cells, or a carcinoma consisting Figure 1. Mixed composition of squamous cell carci- noma and spindle cell carcinoma (HE, x100).
Table 1. Clinical data in six patients with pleomorphic carcinoma.
History of smoking
No Age (y) Sex Smoking status (pack-years) Symptoms
1 64 M Smoker 90 Chest pain, weight loss
2 48 M Smoker 30 Chest pain, cough, sputum, weight loss
3 51 M Smoker 40 Chest pain
4 57 F Nonsmoker - Chest pain
5 63 M Smoker 50 Chest pain, haemoptysis
6 43 F Nonsmoker - Haemoptysis
Table 2. CT and bronchoscopy findings.
CT findings Bronchoscopy findings
No Involved lobe Finding Location Appearance
1 Right upper Atelectasis Right upper Mass
2 Posterior segment of right upper Mass - Normal
3 Left lower Nodule Left lower Mass
4 Left upper Mass Apicoposterior segment Mass
of left upper
5 Left upper Mass - Normal
6 Superior segment of right lower Mass - Normal
only of spindle and giant cells”. Pleomorphic component should comprise at least 10% of the neoplasm (1). According to this definition, we detected only six cases of pulmonary pleomorp- hic carcinoma during five years. More than 1000 cases with primary lung cancer were diagnosed annually in our center. These results pointed out that this tumor was a rare tumor of the lung.
Pleomorphic carcinomas occur mainly in men who smoke heavily (5,7-9). The male-female ra- tio was 3.1:1 and 9:1 in two previous reports (5,7). In a previous study of 75 cases of pulmo- nary carcinoma with pleomorphic, sarcomatoid, or sarcomatous elements, 92% of the patients we- re smoker (8). The patients’ age ranged from 31 to 84 years, with a mean age of 57 years (7). In our series, the male-female ratio was 2:1 and 67%
of the patients were smoker. The mean age of our patients was 54.3 years. Chang et al. reported that all patients were symptomatic (2). The most frequent symptoms were cough, haemoptysis, chest pain and weight loss in previous reports (2,5,7). Chest pain was the most frequent symp- tom in the present study. Pleomorphic carcinoma frequently presents as peripheral lesion. It also showed a predilection for the upper lobes (5,7).
Similarly, tumor showed peripheral localization and a predilection for upper lobes in our series.
The diagnosis of pleomorphic carcinoma was frequently made with thoracotomy (5,10). Kim et al. reported that percutaneous needle biopsy revealed the diagnosis of pleomorphic carcino- ma in none of their patients (5). In our series, the diagnosis was made with thoracotomy in five cases and with cutting needle biopsy in one ca- se. Bronchoscopic examination detected endob- ronchial mass lesion in three cases. Although bronchoscopic biopsies revealed a diagnosis of lung cancer in two cases it was insufficient to di- agnose a tumor of the lung as pleomorphic car- cinoma. According to our opinion, the diagnosis of mixed tumors such as pleomorphic carcino- ma with bronchoscopy is difficult because bronchoscopic biopsies can yield small amount of tissue for pathological examination. Epithelial component was squamous cell carcinoma in three cases and adenocarcinoma in the other three cases in the present study. Chang et al. de- termined that epithelial component was adeno- carcinoma in nine patients, squamous cell car- Table 3. Clinical data including diagnosis, pathology, stage and treatment on six patients of pleomorphic carcinoma. NoDiagnostic methodClinical stagePathologic stageMetastasesEpithelial componentTherapySurvival 1ThoracotomyT2N0M0T2N1M0Hiler lymph nodesAdenoRight pneumonectomyDied 2 months 2ThoracotomyT2N0M0T2N0M0NoAdenoLeft upper lobectomyDied 20 months 3ThoracotomyT2N0M0T2N1M0Hiler lymph nodesSquamousLeft lower lobectomy + Unknown Chemotherapy 4Cutting needle biopsyT2N0M1-Bone metastasesSquamousChemotherapyDied 2 months after 5ThoracotomyT2N0M0T2N0M0NoSquamousLeft upper lobectomyDied 10 months 6ThoracotomyT2N0M0T2N0M1Satellite nodule in AdenoRight pneumonectomy + Died 8 months different lobeChemotherapy
cinoma in four cases and undifferentiated carci- noma in three cases (2). According to Kim et al., the most frequent epithelial component was large cell carcinoma, followed by squamous cell carcinoma (7). Immunohistochemical staining may play a role in establishing the diagosis of pleomorphic cell carcinoma of the lung in ins- tances where carcinomatous differentiation is poor at the light microscopic level (2,10). Seve- ral antibodies are used to differentiate compo- nents of pleomorphic carcinoma (2,8-12). Vi- mentin and cytokeratin are the most common used antibodies for immunohistochemical sta- ining. While epithelial cells were stained with ke- ratin, spindle cells were stained with vimentin (2,8,10). Immunohistochemical studies inclu- ding vimentin and keratin were performed in our three cases. The carcinomatous component was positive for keratin and negative for vimentin and the spindle cell component was positive for vimentin and negative for keratin in these cases.
Many reports pointed that these tumors invade mediastinal structures, pleura and chest wall, and show signs of early distant metastases (2,4,5,7). It was reported that 15 of 30 patients had T3 and/or N1-N2 disease (7). Chang et al.
studied 16 cases of pulmonary pleomorphic car- cinoma (2). Their series included nine inoperab- le and seven operable cases. Among seven pa- tients who underwent surgical resection, four of them had mediastinal, pleural and chest wall in- vasions and three of them had regional lymph node metastases. Our two patients had Stage IV disease. There were two patients with N1 dise- ase. None of our patients had N2 disease. We estimated survival for five patients. In our study, survival time was two months in two patients, eight months in one patient, 10 months in one patient and 20 months in one patient. It is ac- cepted that these tumors have poor prognosis (2,5). It was reported that 6 of 10 patients died within 5 months after surgery (5). Chang et al.
found that the median survival was 3 months (2). A previous report determined a median sur- vival time of 10 months (3). Raveglia et al. re- ported that 16 of 20 patients with pleomorphic carcinoma died from early distant metastases (13). In their series, the median duration of dise- ase-free survival was 5 months and the median duration of overall survival was 8 months.
In conclusion, pleomorphic carcinoma is a rare tumor of the lung. Diagnosis is frequently estab- lished with thoracotomy. These tumors have po- or prognosis.
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