Visceral pleural invasion in lung cancer: recognizing histologic parameters that impact staging and prognosis

Visceral pleural involvement (VPI) is a critical component in the staging of non-small cell lung carcinoma (NSCLC). Tumors < or =3 cm that involve the visceral pleura are classified as T2 lesions, underscoring the prognostic significance of this histologic parameter. Accurate staging of small NSCLCs depends on appropriately assessing the presence or absence of VPI. Elastic stains can be instrumental in detecting disruptions of the visceral pleural elastic layer by tumor, a finding that has prognostic and staging implications similar to tumor that is present on the visceral pleural surface.     

The diagnosis and significance of visceral pleural invasion in lung carcinoma. Histologic predictors and the role of elastic stains

Invasion of the visceral pleura is an important component of lung carcinoma staging, and in some studies is an independent prognostic indicator. Evaluation of invasion by H&E may be indeterminate. Elastic stains can be helpful but are performed rarely. We reviewed all lung carcinoma resections from 1993 for 13 histologic features potentially predictive of pleural invasion. Of 57 resections, 20 were indeterminate by H&E. Verhoeff-Van Gieson (VVG) stain revealed invasion in 8 cases, increasing the pathologic stage in 1. VVG stain was negative in 12 cases, 2 of which had been falsely reported as positive, decreasing the stage in 1. Angiolymphatic invasion and single-cell spread were significant predictors of invasion. Absence of both or the presence of intervening aerated parenchyma predicted lack of involvement in all cases. Elastic stains can provide prognostically important information, changing the pathologic stage in 4% of lung carcinoma resections overall and in 10% of cases indeterminate by H&E for pleural invasion.     

The significance of pleural elastica invasion by lung carcinomas.

Invasion of visceral pleura by primary lung carcinomas is an important parameter in staging. The complex histology of visceral pleura requires special elastic stains for proper evaluation, yet only approximately 10% of peripheral lung carcinomas seen in consultation (S.J.U.) are thus assessed. The objective of this study was to examine the prognostic importance of microscopic visceral pleura invasion by lung carcinomas. Retrospective analysis of 23 cases of peripheral T2, N0, M0 carcinomas with microscopic pleural invasion on elastic stains and a matched control group documented a statistically significant (P = 0.0236) difference in survival between squamous cell carcinoma subgroups. This study therefore suggests the need for histologic assessment of peripheral lung carcinomas for invasion of internal pleural elastic lamina.     

Clinicopathology of stromal invasion in lung adenocarcinoma

In the World Health Organization classification, lung adenocarcinoma with mixed subtypes is defined as invasive carcinoma with evidence of vascular, pleural, or stromal invasion. The histological criteria for stromal invasion, however, are not clearly established. A total of 157 peripheral pure bronchioloalveolar carcinoma (BAC) or lung adenocarcinoma with mixed BAC and others were reviewed. All cases had been resected between 1986 and 2000 and measured ≤30 mm in maximum dimension. Destruction of alveolar framework (DAF) was defined as distortion or discontinuity of the alveolar framework by tumor growth. The extra-alveolar area involvement (EAAI) was defined as tumor growth outside the alveolar framework, which includes the following areas: bronchial wall, perivascular connective tissue and/or the vascular wall, interlobular septum and the visceral pleura. Survival of patients with adenocarcinoma without DAF ( n  = 41) was 100%. Even when adenocarcinoma involved DAF and lacked EAAI ( n  = 21), survival was 100%. The 5 year survival rate of groups with two invasion signs ( n  = 34) was 90.1%, and that of groups with three to five invasion signs ( n  = 61) was 66.7%. Tumor growth outside the alveolar framework is the hallmark of stromal invasion.     

Multiple cavernous hemangiomas of the lung: a case report and review of the literature

Cavernous hemangiomas are benign vascular tumors most commonly seen in the head and neck region in childhood. They have been described rarely in the lungs. We describe a patient with incidental pulmonary nodules discovered at autopsy, which measured up to 0.9 cm and which were present in the lung parenchyma, as well as on the pleura. The nodules were composed of dilated vascular spaces lined by flattened bland cells. Immunohistochemical studies of the lining cells revealed CD34 and factor VIII immunoreactivity, consistent with a lesion of endothelial origin. Taken together, the gross, microscopic, and immunohistochemical findings support the diagnosis of multiple pulmonary cavernous hemangiomas.     

Five years experience with treatment of lung cancer. The role of mediastinoscopy

Over a five-year period, 304 patients with non small cell carcinoma of the lung were evaluated for pulmonary resection. The patients were divided into three groups: 1) 180 patients operated without preoperative mediastinoscopy based on a normal appearing mediastinum on plain chest x-ray; 2) 107 patients with resection of both lung tissue and mediastinal tissue due to localised positive mediastinoscopic findings; 3) 17 patients who were found inoperable either due to poor lung function or diffuse mediastinal seeding. In group 1, 24% were peroperatively found to be inoperable due to mediastinal involvement. The rest were resected and received no further therapy. In group 2, 84 patients were resected and postoperatively irradiated on the mediastinal area. The incidence of bronchopleural fistulae in group 1 was 0.7% and in group 2 16%, and the survival at any period was significantly poorer for group 2 than for group 1. We conclude that every patient with pulmonary infiltrates must be subjected to mediastinoscopy before thoracotomy and should be excluded from operative intervention in the presence of positive mediastinoscopic findings.     

Anisotropic Nature of Mouse Lung Parenchyma

Lung parenchyma is normally considered to be isotropic, that is, its properties do not depend upon specific preferential directions. The assumption of isotropy is important for both modeling of lung mechanical properties and quantitative histologic measurements. This assumption, however, has not been previously examined at the microscopic level, in part because of the difficulty in large lungs of obtaining sufficient numbers of small samples of tissue while maintaining the spatial orientation. In the mouse, however, this difficulty is minimized. We evaluated the parenchymal isotropy in mouse lungs by quantifying the mean airspace chord lengths (Lm) from high-resolution histology of complete sections surrounded by an intact continuous visceral pleural membrane. We partitioned this lung into 5 isolated regions, defined by the distance from the visceral pleura. To further evaluate the isotropy, we also measured Lm in two orthogonal spatial directions with respect to the section orientation, and varied the sample line spacing from 3 to 280 μm. Results show a striking degree of parenchymal anisotropy in normal mouse lungs. The Lm was significantly greater when grid lines were parallel to the ventral–dorsal axis of the tissue. In addition the Lm was significantly smaller within 300 μm of the visceral pleura. Whether this anisotropy results from intrinsic structural factors or from nonuniform shrinkage during conventional tissue processing is uncertain, but it should be considered when interpreting quantitative morphometric measurements made in the mouse lung.     

Invasion of the inner and outer layers of the visceral pleura in pT1 size lung adenocarcinoma measuring ≤3?cm: correlation with malignant aggressiveness and prognosis

Visceral pleural invasion (VPI) is defined as penetration by cancer cells of the elastic layer of the pleura. The purpose of this retrospective study was to compare the effect of invasion of the inner elastic layer of the pleura on survival to that of invasion of the outer elastic layer. One hundred twenty-four pT1 size lung adenocarcinomas were examined for visceral pleural invasion, which was classified into three types: no pleural invasion (NPI), invasion of the inner elastic layer only (IEL), and invasion of both inner and outer elastic layers (OEL). The relationship between the types of VPI and the prognosis was analyzed by univariate and multivariate analyses. Seventy-three (59?%) cancers showed NPI, while 51 cancers showed invasion of the pleura [(IEL) in 26 (21?%), OEL in 25 (20?%)]. The 5-year survival was 81, 60, and 37?% for patients with NPI, IEL, and OEL, respectively. Survival was poorest in patients with OEL (P?<?0.01). Invasion of the outer elastic layer was also significantly associated with lymph node metastasis and frequent lymphatic involvement, micropapillary pattern, higher stromal invasion grade, and presence of small cluster invasion within tumors. Univariate analysis showed a significant relationship between invasion of the outer elastic layer and poor prognosis. However, multivariate analysis identified lymph node metastasis as the most significant predictor of poor prognosis. Analysis of invasion of the inner and outer visceral pleura is important; invasion of the outer elastic layer correlates with poor prognosis in pT1 size lung adenocarcinomas.     

Three cases of adrenocortical tumors mistaken for hepatocellular carcinomas/diagnostic pitfalls and differential diagnosis

Adrenocortical adenomas and carcinomas in other parenchyma are extremely rare, with few cases reported and because of the rarity of these tumors, they occasionally cause problems during diagnosis. Adrenal cortical neoplasms in liver parenchyma can be present in 3 forms, including direct invasion or adhesion to liver parenchyma, tumors arising in adrenohepatic fusion tissue or in ectopic adrenal gland tissue. We report 3 cases of adrenal cortical tumors that were misdiagnosed as hepatocellular carcinoma in the preoperative state. The first case involved an adrenocortical adenoma arising in adrenohepatic fusion tissue. The remaining 2 cases involved an adrenocortical carcinoma and an adrenocortical oncocytoma arising in ectopic adrenal tissue in the liver. We describe the clinical presentations, gross, microscopic findings, immunohistochemical findings with respect to each case, with emphasis on differential diagnosis from hepatocellular carcinoma.     

Multiple peritoneal cytologies collected during laparotomy for gynecologic malignancy

Review of an 18-mo experience with peritoneal cytology specimens showed that 760 peritoneal washings and 177 diaphragmatic smears were collected during 300 laparotomies on patients known to have or suspected of having gynecologic malignancy. One hundred three patients were eventually shown to have benign gynecologic disease. The remaining 197 procedures were done on patients undergoing primary operations for gynecologic malignancy or laparotomies for previously treated gynecologic malignancy. Of the 197 laparotomies for gynecologic malignancies, 168 had washings separately collected from multiple intra-abdominal sites, and these fluids were interpreted as either all positive or all negative in all but seven (4%) patients. The location and extent of the gross or microscopic disease did not correlate with the site of positive washings. Only three of the 177 diaphragmatic smears were positive for malignant cells; these were collected from three patients undergoing primary treatment of ovarian carcinoma, two of whom had extensive peritoneal involvement by carcinoma. Only 35 of the 197 patients with gynecologic malignancy had positive peritoneal cytologies; 32 of these patients had gross or microscopic peritoneal involvement by malignancy, and one additional patient had metastatic carcinoma in pelvic lymph nodes. The analysis of multiple peritoneal washings separately collected from various intra-abdominal sites and the analysis of diaphragmatic smears collected in the absence of gross diaphragmatic disease appear to be of benefit in few cases.     

Malignant pleural mesothelioma: Clinicopathology of 16 extrapleural pneumonectomy patients with special reference to early stage features

The earliest pathological events in the development of malignant pleural mesothelioma (MPM) are not understood. The aim of the present study was to elucidate the early histopathological features of MPM. A total of 16 extrapleural MPM pneumonectomy patients were investigated. Early stage mesothelioma was arbitrarily defined as a tumor ≤5 mm in thickness regardless of the nodal status or other organ involvement. Eight of these patients (six with epithelioid, two with biphasic) had early stage mesothelioma by this definition. Macroscopically there was no visible tumor, but the parietal and visceral pleura were thickened and there was focal adhesion between them. Microscopically, the mesothelioma lesions were multifocal and discontinuous on the pleura. In extremely early cases of epithelioid mesothelioma, tumor cells were generally arrayed in a single layer, but papillary proliferation was observed elsewhere. In sarcomatoid mesothelioma, mesothelioma cells proliferated, forming multiple small polypoid nodules on the pleura. Epithelial membrane antigen was helpful to distinguish reactive from neoplastic mesothelium, but glucose transporter-1 was not. Mesothelioma cells disseminate diffusely throughout the parietal and visceral pleura and mediastinal fat tissue before becoming visible. Stage Ia mesothelioma (neoplasm limited to the parietal pleura) would not be observed in daily practice.     

Solid papillary carcinoma of the breast: imprint cytological and histological findings

Solid papillary carcinoma is a rare breast lesion, but this entity remains poorly recognized. In this article, we report a case of solid papillary carcinoma of the breast with focus on cytological and histological findings. A 66-year-old Japanese woman presented with nipple discharge. Imprint cytology obtained from the surgically resected breast specimens showed a plasmacytoid appearance and spindle cell morphology with low-grade atypia. Histologically, the tumor revealed findings of solid papillary carcinoma and predominantly showed an intraductal lesion with focal minimal invasion into the breast parenchyma. Fibrovascular cores with hyalinization were seen. Proliferation of short spindle cells was also focally observed. Pseudorosette formation or nuclear palisading at the stromal-glandular interface was seen, and intracellular or extracellular mucin deposition was occasionally identified. Nuclear atypia generally showed low grade. Finally, clinicians, cytotechnologists, and pathologists should recognize this rare tumor entity because this tumor is a malignant neoplasm showing characteristic pathological findings.     

Rhabdomyomatosis of the newborn lung unassociated with other malformations

 

Aims:

To describe a case of rhabdomyomatosis of the lung unassociated with other external or visceral malformations in a newborn infant.  

Methods and results:

A 26 weeks' gestation newborn male with no relevant medical or family history presented a well-circumscribed solid area in the posterior mediastinum occupying the upper lobe of the right lung. The possibility of neuroblastoma or an extralobar pulmonary sequestration were excluded after laboratory and arteriographic studies. No visceral anomalies were found. At the age of 9 months the patient underwent a partial lobectomy, and he is free of disease 39 months after surgery. Histological examination demonstrated the presence of numerous bundles of striated fibres arranged haphazardly in the pulmonary interstitium in a background of a type-II congenital cystic adenomatoid malformation-like morphology of the resected lung.  

Conclusion:

The presence of striated muscle fibres in the lung not necessarily represents a lethal congenital malformation. As this case shows, rhabdomyomatosis of the lung can affect a single pulmonary lobe, and resection of the affected lung parenchyma may be curative. It is important for pathologists to be aware of this entity, although it is exceptional, and to include it in the differential diagnosis of pulmonary masses in the newborn lung.     

Wedge resection margin distances and residual adenocarcinoma in lobectomy specimens

We studied 31 T1 N0 M0 peripheral adenocarcinomas diagnosed by wedge resection and treated by lobectomy. Factors recorded were pleural surface-based, gross cut-surface, and microscopic margin distances; morphologic features of the adenocarcinomas; microscopic extension distance of beyond gross perimeter of neoplasm; and presence of residual adenocarcinoma in the lobectomy specimen. All staple-line margins in the wedge and lobectomy specimens underwent complete histologic examination. The mean pleural surface-based, gross cut-surface, and microscopic margin distances in wedge resections were 13.1, 4.1, and 2.3 mm, respectively. The mean microscopic wedge resection margin distance was 11 mm smaller than the pleural surface-based measured margin. The mean microscopic lepidic growth beyond the gross perimeter of the neoplasm was 7.4 mm. Fourteen lobectomy specimens (45%) included adenocarcinoma. The mean microscopic wedge resection specimen margin distances in cases with and without residual adenocarcinoma in the lobectomy specimens were 0.7 and 2.4 mm, respectively (P < .001). Incomplete excision may contribute to higher locoregional recurrence rates following limited resection surgery. Two processes affected wedge resection margin distances: stapling-induced parenchymal stretching, resulting in overestimation of pleural surface-based distances, and microscopic extension of adenocarcinoma beyond the gross perimeter of the neoplasm.     

Invasive ductal carcinoma of the breast associated with extensive melanin melanosis: a case report and review of the literature

Extensive melanosis of breast tissue due to melanin in the absence of involvement by melanoma either primary or secondary has been rarely encountered. Herein we report a first and unique case of extensive macroscopic and microscopic melanosis of mammary parenchyma between carcinoma cells due to melanin in a patient with a poorly differentiated invasive ductal carcinoma of the breast with no evidence of melanocytic differentiation or melanoma. In contrast to previously reported cases in the literature, there is no breach of dermal-epidermal junction and there is no dermal infiltrate in the skin overlying the carcinoma, or Pagetoid disease in the nipple.     

Myeloid diseases in the lung and pleura

Myeloid diseases detected as primary or secondary lesions in the lung and pleura are rare. Clinical presentations and radiographic results may vary significantly depending on the nature of the diseases. The most common diseases associated with lung and pleura involvement are myeloid sarcoma/acute myeloid leukemia (AML) and extramedullary hematopoiesis (EMH). AML typically represents localized involvement by systemic acute leukemia, while EMH is frequently secondary to underlying benign hematolymphoid disorders or myeloproliferative neoplasms. This review provides an overview of the pathogenesis, clinical presentations, radiologic/imaging studies, pathologic and genetic findings, and treatment/outcomes associated with myeloid diseases in the lung and pleura.     

Microscopic anatomy of the visceral fasciae

The term ‘visceral fascia’ is a general term used to describe the fascia lying immediately beneath the mesothelium of the serosa, together with that immediately surrounding the viscera, but there are many types of visceral fasciae. The aim of this paper was to identify the features they have in common and their specialisations. The visceral fascia of the abdomen (corresponding to the connective tissue lying immediately beneath the mesothelium of the parietal peritoneum), thorax (corresponding to the connective tissue lying immediately beneath the mesothelium of the parietal pleura), lung (corresponding to the connective tissue under the mesothelium of the visceral pleura), liver (corresponding to the connective tissue under the mesothelium of the visceral peritoneum), kidney (corresponding to the Gerota fascia), the oesophagus (corresponding to its adventitia) and heart (corresponding to the fibrous layer of the pericardial sac) from eight fresh cadavers were sampled and analysed with histological and immunohistochemical stains to evaluate collagen and elastic components and innervation. Although the visceral fasciae make up a well‐defined layer of connective tissue, the thickness, percentage of elastic fibres and innervation vary among the different viscera. In particular, the fascia of the lung has a mean thickness of 134 μm (± 21), that of heart 792 μm (± 132), oesophagus 105 μm (± 10), liver 131 μm (± 18), Gerota fascia 1009 μm (± 105) and the visceral fascia of the abdomen 987 μm (± 90). The greatest number of elastic fibres (9.79%) was found in the adventitia of the oesophagus. The connective layers lying immediately outside the mesothelium of the pleura and peritoneum also have many elastic fibres (4.98% and 4.52%, respectively), whereas the pericardium and Gerota fascia have few (0.27% and 1.38%). In the pleura, peritoneum and adventitia of the oesophagus, elastic fibres form a well‐defined layer, corresponding to the elastic lamina, while in the other cases they are thinner and scattered in the connective tissue. Collagen fibres also show precise spatial organisation, being arranged in several layers. In each layer, all the fibrous bundles are parallel with each other, but change direction among layers. Loose connective tissue rich in elastic fibres is found between contiguous fibrous layers. Unmyelinated nerve fibres were found in all samples, but myelinated fibres were only found in some fasciae, such as those of the liver and heart, and the visceral fascia of the abdomen. According to these findings, we propose distinguishing the visceral fasciae into two large groups. The first group includes all the fasciae closely related to the individual organ and giving shape to it, supporting the parenchyma; these are thin, elastic and very well innervated. The second group comprises all the fibrous sheets forming the compartments for the organs and also connecting the internal organs to the musculoskeletal system. These fasciae are thick, less elastic and less innervated, but they contain larger and myelinated nerves. We propose to call the first type of fasciae ‘investing fasciae’, and the second type ‘insertional fasciae’.     

Pulmonary mesothelioma in bronchioalveolar lavage: a case report

Mesothelioma is a neoplasm arising from the mesothelial cells lining the body serosal surfaces. The frequent primary sites include the pleura followed by the peritoneum and rarely the pericardium. Pleural mesothelioma encases the lung and fills the pleural space, which limits the lungs' ability to expand. The initial diagnosis requires the presence of characteristic clinical, radiological, and pathological features. A thorough review of the English language literature found no reports where a diagnosis of mesothelioma was made on material originating from bronchioalveolar lavage (BAL). We report a case of lung parenchymal involvement by mesothelioma shedding cells in BAL specimen.     

Intraductal papillary mucinous neoplasm

Intraductal papillary mucinous neoplasm (IPMN) is a grossly visible (≥1 cm), mucin-producing neoplasm that arises in the main pancreatic duct and/or its branches. Patients with intraductal papillary mucinous neoplasm can present with symptoms caused by obstruction of the pancreatic duct system, or they can be asymptomatic. There are 3 clinical subtypes of intraductal papillary mucinous neoplasm: main duct, branch duct, and mixed. Five histologic types of intraductal papillary mucinous neoplasm are recognized: gastric foveolar type, intestinal type, pancreatobiliary type, intraductal oncocytic papillary neoplasm, and intraductal tubulopapillary neoplasm. Noninvasive intraductal papillary mucinous neoplasms are classified into 3 grades based on the degree of cytoarchitectural atypia: low-, intermediate-, and high-grade dysplasia. The most important prognosticator, however, is the presence or absence of an associated invasive carcinoma. Some main duct-intraductal papillary mucinous neoplasms progress into invasive carcinoma, mainly tubular adenocarcinoma (conventional pancreatic ductal adenocarcinoma) and colloid carcinoma. Branch duct-intraductal papillary mucinous neoplasms have a low risk for malignant transformation. Preoperative prediction of the malignant potential of an intraductal papillary mucinous neoplasm is of growing importance because pancreatic surgery has its complications, and many small intraductal papillary mucinous neoplasms, especially branch duct-intraductal papillary mucinous neoplasms, have an extremely low risk of progressing to an invasive cancer. Although most clinical decision making relies on imaging, a better understanding of the molecular genetics of intraductal papillary mucinous neoplasm could help identify molecular markers of high-risk lesions. When surgery is performed, intraoperative frozen section assessment of the pancreatic resection margin can guide the extent of resection. Intraductal papillary mucinous neoplasms are often multifocal, and surgically resected patients should be followed for metachronous disease.