(Pathweb) Microscopic images : Image1 ; Image2 ; Image3 ; Image4 .

This study attempts to evaluate the clinicopathologic features of mixed subtype adenocarcinomas and the prognostic implications of histopathology classifications. Surgical specimens from 141 patients with clinical stage I or II lung adenocarcinoma during the period 1992-2004 were included. These cases were classified into four groups defined by the extent of the bronchioloalveolar carcinoma component: group I: pure bronchioloalveolar carcinoma; group II: mixed subtype with predominant bronchioloalveolar carcinoma component and < or = 5 mm invasive component; group III: mixed subtype with bronchioloalveolar carcinoma component and > 5 mm invasive component; group IV: invasive carcinoma with no bronchioloalveolar carcinoma component. Descriptive statistics were used to examine the groups with respect to age, tumor size, lymph node metastasis, and Ki-67 and p53 expression levels. Death rate for the groups was obtained by patient's charts and from the National Death Index database. The population was similar in age, tumor size and lymph node metastasis. Immunohistochemical results showed that the mean Ki-67 labeling and the amount of p53 overexpression had the same trend of increasing mean values or positive results from groups I to IV. The reported proportion of deaths ranged from 0% for groups I and II, 20% in patients with predominant invasive component with bronchioloalveolar carcinoma (group III), and 18% in patients with invasive carcinomas and no bronchioloalveolar carcinoma component (group IV). The difference between the proportion of patients with reported deaths in the time period of this study in the combined greater than 5 mm+pure invasive groups (groups III, IV), and the < 5 mm + noninvasive groups (groups I, II) is statistically significant. These results suggest that histological features may be useful in defining categories of lung adenocarcinomas with differing survival and prognostic features. These results are helpful in defining a subcategory of 'minimally invasive adenocarcinoma', which has features similar to bronchioloalveolar carcinoma.

Small peripheral pulmonary adenocarcinoma: morphologic and molecular update. Adv Anat Pathol. 2007 Mar;14(2):120-8.

The dichotomous histopathologic separation of lung carcinoma into "small cell" and "nonsmall cell" categories is validated by marked clinical and biologic differences between these groups of tumors. However, nonsmall cell carcinoma represents a heterogenous group of tumors, and the subclassification of nonsmall cell lung carcinoma at the molecular, morphologic, and epidemiologic levels has led to the promise of precise treatment and better prognostication. Histomorphologic aspects of small peripheral adenocarcinomas that represent good prognosis include pure bronchioloalveolar carcinoma, minimal invasion within a mixed invasive and lepidic growth pattern tumor, and minimal scar within a lepidic growth pattern tumor. Activating mutations and increased gene copy number of the epidermal growth factor receptor protein and locus, respectively, have been shown to help predict responsiveness to small molecule receptor tyrosine kinase inhibitors in lung adenocarcinoma. These important concepts of morphology and molecular pathology are reviewed, and recommendations for application of these concepts to the practice of surgical pathology are provided.

 

Pulmonary adenocarcinoma: the expanding spectrum of histologic variants. Arch Pathol Lab Med. 2006 Jul;130(7):958-62.

Pulmonary adenocarcinoma is one of the most common types of lung cancer. Traditionally, adenocarcinomas have been divided based on their degree of resemblance to their parent tissues into 3 histopathologic types: well, moderately, and poorly differentiated. In the majority of cases, this schema is sufficient to categorize these lung tumors. However, there is a considerable group of tumors in which the histology is not that of the classic gland-forming neoplasm. Thus, although the terminology of adenocarcinoma is applied in such cases, the histopathologic features are different from those of the more conventional variants. The current review addresses these unusual variants and the importance of recognizing and properly categorizing them to avoid unnecessary additional workup or possible misdiagnosis.

Primary lung carcinoma with signet-ring cell carcinoma components: clinicopathological analysis of 39 cases.Am J Surg Pathol. 2004 Jul;28(7):868-74.

The clinical and histologic profiles of primary lung carcinomas with signet-ring cell carcinoma (SRCC) components were analyzed. The SRCC components were seen in 39 cases (1.5%) of 2640 cases of surgically resected primary lung carcinomas. The patients' mean age was 54.6 years (range, 32-76 years), and the male-to-female ratio was 1.16:1.00. Twenty-six patients (66.7%) were smokers. The SRCC component was seen as part of an adenocarcinoma in 36 cases (acinar, 27 cases; mixed bronchioloalveolar and acinar, 9 cases) and as part of an adenosquamous cell carcinoma in 2 cases; one lesion consisted of only SRCC cells. The morphologic appearance of cancer nests containing SRCC was classified into three patterns: solid, tubuloacinar, and discohesive. Each case was composed of a varying proportion of these three patterns. The carcinomas with SRCC components were divided into two groups, according to those in which the SRCC component occupied <50% of the lesion (L-SRCC; n = 20) and those in which the SRCC component occupied > or = 50% of the lesion (H-SRCC; n = 19). The frequencies of blood vessel invasion, lymph vessel invasion, and lymph node metastasis were significantly higher in the H-SRCC group than in 1634 adenocarcinoma, and adenosquamous cell carcinomas (non-SRCC). The 5-year survival rates of patients non-SRCC, with l-SRCC, or with H-SRCC were 52.7%, 50%, and 28.4%, respectively. The 5-year survival rate of patients with H-SRCC and of patients without SRCC were significantly different. Based on these clinicopathologic characteristics, we classified primary lung carcinomas with SRCC components into the following two groups: 1) SRCC, in which the SRCC component occupies >or = 50% of the lesion, and 2) signet-ring feature, in which the SRCC components occupies <50% of the lesion.

Peripheral lung adenocarcinomas: 10 mm or less in diameter.Ann Thorac Surg. 2003 Aug;76(2):350-5.

BACKGROUND: Few reports have been published regarding peripheral lung adenocarcinomas that are 10 mm or less in diameter. This is considered to be the smallest tumor size detectable by present diagnostic modalities. METHODS: Clinicopathologic studies were performed in 57 patients with peripheral lung adenocarcinomas of 10 mm or less in diameter. Outcomes were compared with two other groups that consisted of 32 patients with adenocarcinomas between 11 and 15 mm in diameter and 35 patients with adenocarcinomas between 16 and 20 mm in diameter. Tumors were curatively resected between 1992 and 2002. RESULTS: The mean age was 61.7 years. The following three features were more frequent: female sex (78.9%), nonsmokers (77.2%), and cases with carcinoma detected by computed tomography despite negative chest radiography (96.5%). Negative lymphatic invasion (94.7%) was significantly higher. Three cases showed lymphatic invasion that was classified as types E or F, according to Noguchi's classification. There were no cases of lymph node metastasis, pleural involvement, or intrapulmonary metastasis. Well-differentiated type was in 93.0%. Types A and B, which are noninvasive alveolar replacement-type adenocarcinomas, were significantly dominant (86.0%). The 5-year postoperative survival rate was 97.3%, which was significantly better than in the other two groups (75.5%, 78.1%). CONCLUSIONS: Histopathologic features of most peripheral lung adenocarcinomas of 10 mm or less in diameter were types A and B. Types A and B were considered fundamentally indicated for thoracoscopic wedge resections. However, the other types required the standard operation.

A case of adenocarcinoma of the lung with a spindle cell component. Acta Pathol Jpn. 1992 Nov;42(11):841-6.

We report a 60-year-old man, who was admitted to the hospital with complaints of cough and sputum. His chest x-ray showed an abnormal mass in the right upper lobe. After admission he noticed the painful gingival tumor. Right upper lobectomy and resection of the gingival tumor were performed. Their histological features showed that the tumor consisted of a papillary and tubular adenocarcinoma mixed with a component of spindle cells. Immunohistochemical study demonstrated a positive reaction in the epithelial component for keratin and epithelial membrane antigen, and not only these epithelial markers but also vimentin were expressed in some spindle tumor cells. Electron microscopic study confirmed the biphasic pattern, showing gland formation and undifferentiated cells. We diagnose this case as adenocarcinoma of the lung with a spindle cell component and the gingival tumor was metastatic. Autopsy showed that metastatic lesions were found in the left adrenal gland and in the left kidney. The tumor cells in the left adrenal gland were composed of spindle cells and the tumor in the left kidney showed gland formation. Immunohistochemical and electron microscopic findings of surgical and autopsy specimen suggest that this tumor is of epithelial origin, and the spindle cells are derived from immature mesenchymal cell transformation of epithelial cells.
 

Adenocarcinoma of the lung: a comparative diagnostic study using light and electron microscopy. Hum Pathol. 1988 Aug;19(8):910-3.

Several techniques for diagnosing adenocarcinoma of the lung are commonly available, but the frequency of their use and diagnostic sensitivity may vary. Twenty cases of primary lung adenocarcinoma obtained at surgery were studied by the following four routine techniques: light microscopy (LM) using hematoxylin-eosin (H&E) stain, mucicarmine stain, and PAS-diastase stain, and electron microscopy (EM). Three observers independently determined the positivity (0 [none], +/- [equivocal], 1 + [slight], 2 + [moderate], 3 + [marked]) of each of these cases for lumen formation in H&E-stained sections (LM lumens), intracytoplasmic (cytoplasmic mucicarmine) or intraluminal (luminal mucicarmine) mucicarmine, intracytoplasmic (cytoplasmic PAS) or intraluminal (luminal PAS) PAS-diastase, and lumen formation (EM lumens) or microvilli (EM microvilli) on electron microscopy. Comparative matching of these seven microscopic determinants (using Wilcoxon signed-rank test) demonstrated significant (P less than .01) sensitivity of EM microvilli over EM lumens, EM microvilli over luminal mucicarmine, cytoplasmic PAS over luminal mucicarmine, EM microvilli over cytoplasmic mucicarmine, cytoplasmic PAS over cytoplasmic mucicarmine, and EM microvilli over LM lumens, and a significant (P less than .05) sensitivity of cytoplasmic PAS over LM lumens, EM microvilli over luminal PAS, luminal PAS over luminal mucicarmine, and cytoplasmic PAS over EM lumens. Friedman's nonparametric test (P less than .05) indicated a significant difference among the microscopic determinants. The most sensitive was EM microvilli (mean rank score, 5.17) followed by cytoplasmic PAS (4.77), luminal PAS (4.02), cytoplasmic mucicarmine (3.62), LM lumens (3.52), EM lumens (3.47), and luminal mucicarmine (3.40). However, each of the diagnostic techniques had case examples positive for one, but not for the others, indicating that maximum yield of adenocarcinoma diagnoses will be obtained by performing all four techniques (H&E, mucicarmine, PAS-diastase, and electron microscopy.

A scanning and transmission electron microscopic study of pulmonary adenocarcinoma with histological correlation.Acta Pathol Microbiol Immunol Scand [A]. 1982 Nov;90(6):463-70.

The three-dimensional growth pattern and cell shape and surface of 26 adenocarcinomas of the lung were studied by scanning electron microscopy. The prevailing subtype according to the WHO histological classification, grade of differentiation and secretion of mucosubstances were determined by light microscopy, the tumour cells being further characterized by transmission electron microscopy. The series included 5 acinar, 12 papillary, 1 bronchiolo-alveolar and 8 solid subtypes of adenocarcinoma. Out of these 5 acinar, 9 papillary and 1 bronchiolo-alveolar carcinomas were well or moderately, and 1 solid carcinoma was moderately differentiated. One acinar, 2 papillary and 7 solid carcinomas were poorly differentiated. All tumours secreted mucosubstances, which in the solid carcinomas occurred as intracytoplasmic vacuoles. In acinar adenocarcinomas there were columnar tumour cells surrounded by fibrotic stroma. In the papillary and bronchiolo-alveolar subtypes the tumour cells formed papillary nodules along the alveolar walls while the solid subtype showed no organized structures. The tumour cells were mostly cylindrical or club-shaped in well and moderately differentiated and spherical in less differentiated neoplasms. In well differentiated papillary carcinomas the tumour cells were tightly attached to each other, whereas many moderately and all poorly differentiated carcinomas had broad intercellular spaces. Tumour cells with microvilli occurred more often in the acinar, papillary and bronchiolo-alveolar subtypes, which were mostly well or moderately differentiated, than in the mostly poorly differentiated solid subtype of pulmonary adenocarcinoma, which often had a rough apical surface with microridges. In conclusion the three-dimensional growth pattern corresponded fairly well with the prevailing histological subtype and the surface structure of cancer cells seemed to reflect the grade of differentiation in pulmonary adenocarcinomas.

The relationship of histological type and tumor location to prognosis in 1000 patients with lung resection with special reference to adenocarcinoma. Pneumologie. 1990 Dec;44(12):1287-93.

On the basis of clinical investigations of 1,000 resected lung cancer patients we comment on the prognostic implications of histological type and tumour localisation with special regard to adenocarcinoma. 1. 198 patients, resected for primary adenocarcinoma of the lung, had 5- and 10-year survival rates of 42% and 25.3% respectively, similar to the survival rate of patients who had been operated on for squamous cell carcinoma. 2. Of 6 patients suffering from central adenocarcinoma according to WHO classification of 1967, or 10 patients according to WHO classification of 1981, not a single patient survived for more than 3 years. In patients with peripheral adenocarcinoma the survival rates after 5 and 10 years amounted to 42.4% and 26.6%. The 5-year survival rates of all patients with peripheral cancers were significantly better than those of central tumour patients. 3. The survival rates after 5 and 10 years among patients resected for primary adenocarcinoma dropped steeply in relation to tumour stage. While adenocarcinoma patients in stage I had the highest survival chances in comparison to other types, the survival curve of stage III patients with this type fell below that of small-cell and large-cell cancer patients. 4. The prognosis of patients resected for adenocarcinoma whose x-ray pictures showed a large infiltration, had a bad prognosis. Patients with peripheral coin lesions had good survival chances. 5. It was impossible to demonstrate a correlation between survival rate and grade of differentiation in adenocarcinoma patients. There were also no prognostic differences between papillary and acinar subtype. Patients with bronchiolo-alveolar carcinoma had the significantly highest survival rates.