Optimal immunohistochemical markers for distinguishing lung adenocarcinomas from squamous cell carcinomas in small tumor samples

The histologic subtype of non-small cell lung carcinoma is important in selecting appropriate chemotherapy for patients with advanced disease. As many of these patients are not operative candidates, they are treated medically after biopsy for diagnosis. Inherent limitations of small biopsy samples can make distinguishing poorly differentiated lung adenocarcinoma (ADC) from squamous cell carcinoma (SCC) difficult. The value of histochemical and immunohistochemical markers to help separate poorly differentiated ADC from SCC in resection specimens is well established; however, the optimal use of markers in small tissue samples has only recently been examined and the correlation of marker expression in small tissue samples with histologic subtype determined on resection specimens has not been well documented. We address this issue by examining the expression of 9 markers (p63, TTF1, CK5/6, CK7, 34βE12, Napsin A, mucicarmine, NTRK1, and NTRK2) on 200 cases of ADC and 225 cases of SCC in tissue microarray format to mimic small tissue specimens. The single best marker to separate ADC from SCC is p63 (for SCC: sensitivity 84%, specificity 85%). Logistic regression analysis identifies p63, TTF1, CK5/6, CK7, Napsin A, and mucicarmine as the optimal panel to separate ADC from SCC. Reduction of the panel to p63, TTF1, CK5/6, and CK7 is marginally less effective but may be the best compromise when tissue is limited. We present an algorithm for the stepwise application of p63, TTF1, CK5/6, CK7, Napsin A, and mucicarmine in situations in which separation of ADC from SCC in small specimens cannot be accomplished by morphology alone.     

A combined small cell carcinoma of the lung containing three components: small cell, spindle cell and squamous cell carcinoma.

A 61-year-old man was referred to our hospital because of rapid growth of a mass shadow revealed by chest radiography. The mass was diagnosed as pure small cell carcinoma by CT-guided needle biopsy, and the patient underwent chemotherapy. However, as the tumor showed no response, we considered the possibility of some other form of malignancy and performed surgery. Postoperatively, the mass was diagnosed as small cell carcinoma combined with small cell, spindle cell and squamous cell carcinoma. We report this case in view of the rarity of this combination of morphologic patterns in a primary bronchogenic carcinoma.     

A word of caution regarding napsin A expression in squamous cell carcinomas of the lung

Napsin A is a novel peripheral airway epithelial marker that, because it is commonly expressed in lung adenocarcinomas but absent in squamous cell carcinomas, is considered to be useful in distinguishing between these 2 types of tumors. Recent immunohistochemical studies, however, have reported napsin A expression in up to 26% of squamous cell carcinomas of the lung, a finding that indicates that this marker may not be as specific for lung adenocarcinomas as is generally believed. To determine the causes of the discrepancies between some recent immunohistochemical studies and previous reports on napsin A expression in squamous cell carcinomas of the lung, 90 pulmonary and 64 nonpulmonary squamous cell carcinomas (20 skin, 10 esophagus, 7 uterine cervix, and 27 from the head and neck region) were investigated by immunohistochemistry for this marker. None of the 90 squamous cell carcinomas of the lung exhibited napsin A positivity in the neoplastic cells; however, because strong napsin A reactivity was observed in hyperplastic type II pneumocytes and in intra-alveolar macrophages, both of which were sometimes seen entrapped within the tumor, it has been concluded that the presence of these entrapped cells was the most likely cause of the discrepancies. Pathologists should be aware of this potential pitfall in the interpretation of the immunostaining for napsin A, especially when small lung biopsy specimens, tissue microarrays, or cytology specimens are being evaluated.     

Miniresection of small peripheral carcinomas of the lung

A total of 499 miniresective procedures were done for lung carcinoma over a 29-year period to July 1986. The operations were carried out in three groups: patients in whom a previous resection had been done, patients with stage III carcinoma, and those with stage I or II disease. Overall, perioperative mortality was 2.4 per cent. Cumulative survival in 296 patients with stage I or II carcinoma was 52 per cent at 5 years, 31 per cent at 10 years, and 11 per cent at 15 years.     

Inverted papillomas and associated squamous cell carcinomas

Inverted papillomas of the nose and paranasal sinuses are found to be associated with squamous cell carcinomas in a small percentage of cases. The records of forty-six patients treated for inverted papillomas in these areas over a 10-year period were reviewed. Eleven patients (24%) were found to have squamous cell carcinoma, and one carcinoma in situ, in relationship to the inverted papillomas. This is a much higher percentage than generally reported. Four of these patients were found to have inverted papillomas coincidentally in surgical specimens resected for squamous cell carcinoma. Patients with squamous cell carcinoma were found to be in older age groups, were more likely to manifest epistaxis than the more common unilateral nasal obstructive symptoms, and had less time between the onset of symptoms and presentation than those with inverted papillomas alone. The clinical presentation, treatment, and outcome of inverted papillomas and squamous cell carcinomas in association with inverted papillomas are discussed.     

Small bilateral renal cell carcinomas

A case of multicentric bilateral small renal cell carcinomas is presented. The two largest tumors were detected by computerized tomography (CT) and the diagnosis confirmed by ultrasound and fine needle biopsy.     

Thymic carcinoma (mixed small cell undifferentiated squamous cell carcinoma); report of a case

A 52-year-old man was admitted to our hospital on October, 1997 with complains of left anterior chest pain. A chest X-ray and computed tomography on admission showed evidence of a mass in the left anterior mediastinum. The patient was treated with combination chemotherapy [cisplatin (CDDP), etoposide (VP-16)] and radiation therapy (2 gray x 25 days), preoperatively. Median sternotomy revealed a tumor invading into the left anterior chest wall, the pericardium, and partial pleura. The tumor was extirpated with combined resection of invaded organs. Microscopically and immunohistochemically, the tumor was diagnosed mixed small cell and undifferentiated squamous cell carcinoma documented by Snover et al. The patient was discharge on March 1998, but 2 years later after operation, he was dead by recurrent. We reported a rare case of thymic carcinoma.     

Lectin histochemistry of laryngeal squamous cell carcinomas

A panel of five biotinylated lectins was applied to study the presence and distribution of membrane carbohydrate residues in the normal laryngeal epithelium and in laryngeal squamous cell carcinomas (SCCs) of 86 patients with the avidin-biotin peroxidase complex technique. The lectin-binding pattern of well-differentiated SCCs was comparable to that of the spinous cells of the normal laryngeal epithelium. In the less differentiated SCCs, staining of the keratinocyte plasma membrane with lectins was either reduced or absent, indicating a decline in the glycosylation of cell surface glycoconjugates. The lectins applied here could be used in the rapid assessment of less-differentiated areas within a laryngeal SCC, but they cannot be regarded as reliable markers of laryngeal keratinocytes undergoing malignant transformation. (Otolaryngol Head Neck Surg 1998;118:886-91.)     

A case of lung squamous cell carcinoma with metastases to the duodenum and small intestine

Gastrointestinal metastasis of lung cancer is fairly rare, and metastasis to the duodenum is very uncommon. We report a case of duodenum and small intestine metastases of lung squamous cell carcinoma. The patient was a 66-year-old man. He was diagnosed with lung squamous cell carcinoma (T4N3M1 [mediastinum, cervical lymph node, and duodenum metastases], stage IV). He noted a sense of abdominal fullness on the evening of the day chemoradiotherapy was given, and emergency surgery was performed for suspected perforation of the digestive tract. Intraoperative findings included a tumor in the small intestine with a perforation at the tumor site; partial resection of the small intestine, including the tumor, was performed. Small intestine metastasis of lung cancer was diagnosed following histopathologic examination. When lung cancer patients complain of abdominal symptoms, it is important to consider gastrointestinal metastases in diagnosis and treatment.     

Collision cancer of squamous cell carcinoma and small cell carcinoma of the lung; report of a case

We report a rare case of a primary collision cancer in the lung consisting of squamous cell carcinoma and small cell carcinoma. A 65-year-old man with an abnormal shadow in the right S6 was diagnosed as squamous cell carcinoma by transbronchial lung biopsy. A right lower lobectomy with mediastinal lymph node dissection was performed. The pathological stage of squamous cell carcinoma was IIIA (T2N2M0). The other element diagnosed by pathological examination was small cell carcinoma of which pathological stage was IA (T1N0M0). Each element was clearly distinguished and touched each other. Following the operation, the patient received systemic chemotherapy against small cell carcinoma with cisplatin and irinotecan hydrochloride for 1 course, and cisplatin and etoposide for 3 courses. Since the prognosis of collision cancer is generally reported to be influenced by more advanced element of cancer, the prognosis of the present case is suspected to be dependent on the squamous cell carcinoma.     

"Composite" tumor--mixed squamous cell and small-cell anaplastic carcinoma of the larynx

Mixed squamous and oat cell carcinomas (composite neoplasms) of the larynx behave aggressively with a propensity toward early dissemination. Diagnosis may not be made until definitive surgery is performed. The extent of surgery must be determined by the size and site of the primary neoplasm and the physiologic status of the patient. In our experience, surgery has adequately controlled the primary disease. A metastatic work-up is essential. Entry into a comprehensive program employing adjunctive radiotherapy and chemotherapy are strongly recommended. Theories concerning histogenesis remain controversial and include two separate colliding tumors, differentiation from a single cell line, or divergent differentiation of a single cell line.     

Mucoepidermoid and squamous cell carcinomas of breast with reference to squamous metaplasia and giant cell tumors

Clinical and pathologic features of five low-grade mucoepidermoid and a similar number of squamous cell carcinomas of breast are presented. Three of each were retrieved from 55 cases of invasive breast cancer previously assessed to exhibit squamous metaplasia. Although the estimated incidence of low-grade mucoepidermoid cancers is approximately 0.2%, they may be more frequent, masquerading under designations of squamous metaplasia or intracystic carcinomas. All patients with low-grade mucoepidermoid cancer, and the two recorded previously, were free of recurrence for 4-10 years. No high-grade mucoepidermoid cancers were found. Squamous cell cancers frequently have a phyllode configuration (carcinoma phyllodes). Two examined by electron microscopy revealed a commonality of ultrastructural features with similar tumors of other sites. None exhibited glandular differentiation or tinctorial evidence of mucin secretion. One squamous cell carcinoma contained both malignant epithelial and banal, osteoclast-like, stromal giant cells. Only the latter were identified in tissue culture. This experience and review of the literature prompted a nosologic characterization of giant cell lesions of breast. One patient with squamous cell carcinoma succumbed because of her disease; the remainder are either free of or alive with recurrence at 4 and 10 years.     

Small cell carcinoma of the lung

Prospects for the patient with small cell carcinoma of the lung have been partially turned around during the past decade. This dramatic achievement remains very incomplete, but it continues to gather momentum and seems to carry promise of greater advance in the future. An essential feature of the new approach to treatment is that it depends on cooperative and interdisciplinary effort; in all probability, increasing cooperation will be necessary for future progress. We will attempt to review here the current approaches to the understanding and management of this disease, as they may be of concern to surgeons, and to try to define the areas of failure and controversy.