Papillary adenocarcinoma of lung with psammoma bodies: report of a case derived from type II pneumocytes

A 52-year-old woman underwent thoracotomy for the removal of a mass in the middle lobe of the right lung. Light microscopy showed a tumour with the morphology of a papillary adenocarcinoma with numerous psammoma bodies. Electron microscopy revealed the tumour cells to possess the lamellated intracytoplasmic inclusions characteristic of normal and neoplastic type II pneumocytes. Psammoma bodies have not previously been reported in type II cell carcinoma of the lung. Alveolar cell carcinoma should be considered in the differential diagnosis of a papillary adenocarcinoma with psammoma bodies occurring in the lung.     

Multiple papillary adenomas of type II pneumocytes found in a 13-year-old boy with von Recklinghausen's disease

A case of multiple papillary adenomas of type II pneumocytes is reported. A 13-year-old boy with von Recklinghausen's disease had small nodular lesions in both lungs without symptoms. The biopsied lung contained greyish-white nodules ranging in size from 0.5 to 2 mm. Light microscopic examination revealed cuboidal to low columnar cells arranged in a papillary pattern. Elastic fibres were present in the tumour stroma. Electron microscopically, the cells had osmiophilic lamellar bodies in the cytoplasm and short microvilli along the free border. The tumour cells expressed immunoreactivity for epithelial membrane antigen and surfactant apoprotein antibodies. More than 6 years after open lung biopsy, the patient is well but small nodular shadows can still be identified.     

Presence of apocrine epithelial antigen (AEA) in type II pneumocytes and in hyaline membranes of neonatal RDS

We have investigated the distribution of an apocrine membrane antigen (AEA) in pulmonary tissue using a rabbit antiserum raised against fat globule glycoproteins isolated from human milk. In indirect immunostaining (PAP, IF) of sections from normal lung tissue, the membranes facing the alveolar lumen of cells corresponding to the type II pneumocytes in the alveolar walls were decorated. The selective distribution of AEA to the membranes of type II pneumocytes was confirmed in double immunostaining by identification of these cells with rat antibodies against surfactant apoprotein. In fetal lung tissue, the AEA antigen was detected by the 9th week of gestation. In lung samples from newborns which had died of respiratory distress syndrome (RDS) the intra-alveolar hyaline membranes stained for the AEA antigen. SDS-PAGE of the immunoprecipitate obtained with anti-AEA serum from radiolabelled glycoprotein fraction of normal lung tissue revealed a single band of 79,000 dalton apparent molecular weight. These findings indicate that the AEA constitutes a membrane marker of the type II pneumocytes and might be involved in the secretory process of surfactant. Immunohistological evidence for the presence of AEA in the hyaline membranes of neonatal RDS is also presented.     

Dysfunction of guinea-pig pulmonary surfactant and type II pneumocytes after repetitive challenge with aerosolized ovalbumin

Background Asthma symptoms may partially be caused by a surfactant dysfunction. The inflammatory reaction, so characteristic of asthma, involves a protein invasion of airways which harmfully affects the surfactant function. However, mild asthma attacks might also impede the surfactant synthesis in alveolar type II cells. Objective The present study evaluates the hypothesis that type 11 pneumocyte metabolic function might be disturbed in a model of mild asthma. Methods Immunized, as well as not immunized control guinea-pigs, were challenged three times at two-day intervals with 0.04% ovalbumin aerosol. Bronchoalveolar lavage (BAL) was performed one day after the last challenge and the fluid was evaluated for surface activity, and content of phospholipids and proteins. Alveolar type II cells were isolated and their ability to incorporate a ³H labeled surfactant precursor was evaluated. Results BAL fluid from immunized and challenged animals showed less surface activity (P < 0.01) when compared with BAL fluid from controls, not immunized but challenged. Most likely the reduced surface activity was caused by a 14% increase in the protein concentration (P < 0.05). Isolated type II cells from immunized and challenged animals had 33% less phospholipids than cells from controls (P < 0.05), and phosphatidylcholine synthesis was reduced 35% (P < 0.05). Conclusion Conclusion These results suggest that the synthesis, intra-cellular storage, and biophysical activity of surfactant are decreased in an intermittent and mild form of asthma.     

Reactive type II pneumocytes in bronchoalveolar lavage fluid from adult respiratory distress syndrome can be mistaken for cells of adenocarcinoma

A growing body of literature illustrates that bronchoalveolar lavage is a reliable and efficient means of diagnosing primary and secondary malignancies in the lung. Its safety in severely compromised patients often makes it preferable to other biopsy procedures. However, a variety of reparative and degenerative pulmonary disorders may result in cytologic alterations so severe that pneumocytes resemble cells of malignancy. We describe four patients with the adult respiratory distress syndrome from whom lavage fluid showed gland-like groups of malignant-appearing cells morphologically consistent with adenocarcinoma. Transbronchial biopsy sections in one case and lavage fluid electron microscopy in another showed that these pseudomalignant cells were reactive Type II pneumocytes with surface microvilli, cell junctions, and numerous cytoplasmic myelin figures. Careful clinicopathologic correlation is the best way to ensure accurate diagnosis in these cases.     

Immunocytochemical detection of DNA topoisomerase type II in primary breast carcinomas: Correlation with clinico-pathological features

DNA topoisomerase type II (DT-II) is a major component of interphase nuclear matrix fractions, present in S-phase of the cell cycle. A series of 80 carcinomatous breast surgical samples was evaluated by immunohistochemistry, using a polyclonal antibody in a comparison with Ki-67 antiserum. A correlation with clinico-pathological data was also performed. Infiltrating ductal and lobular carcinomas constantly express DT-II with varying intensity of nuclear staining; a similar immunohistochemical pattern is observed with Ki-67. A frequent co-expression of DT-II and Ki-67 is encountered with double immunostaining; accordingly to these data, a linear relationship is evident when linear regression is employed. In addition, significant relationships between DT-II values and tumour size, histological grade and node involvement are shown, while an inverse correlation is appreciable between DT-II and oestrogen receptors and progesterone receptors. DT-II may be considered to be an additional operational marker for the proliferating fraction of cells in breast carcinomas.     

Papillary urothelial neoplasm of low malignant potential of the urinary bladder: clinicopathologic and outcome analysis from a single academic center

Few long-term single-center studies have addressed the outcome of patients with papillary urothelial neoplasms of low malignant potential. Our study evaluates the behavior of these tumors occurring as primary urinary bladder lesions. For this purpose, 34 primary in-house cases diagnosed and treated between 1998 and 2008 were identified from our medical records. Upon review, 3 cases were upgraded to noninvasive low-grade urothelial carcinomas and excluded from further evaluation. During follow-up (range, 3-108 months; mean, 42 months), 13 patients developed recurrences; and 9 patients progressed to a noninvasive higher grade lesion (8 to low-grade and 1 to high-grade urothelial carcinomas). None of our patients developed stage progression (>pTa) or died of bladder cancer. Size of the primary tumor was associated with the risk of recurrence (P = .043), whereas the number of episodes of recurrence was associated with the likelihood of grade progression (P = .034). In conclusion, recurrences were observed in 42% of all our patients, with a grade progression rate of 29%. None of our patients developed invasive carcinoma or died as a consequence of their disease. Considering the low but definitive risk of recurrence and grade progression, appropriate clinical follow-up of patients with primary papillary urothelial neoplasm of low malignant potential is warranted.     

Molecular basis of mucopolysaccharidosis type II: Mutations in the iduronate-2-sulphatase gene

A number of mutations in the X-chromosomal human iduronate-2-sulphatase gene have now been identified as the primary genetic defect leading to the clinical condition known as Hunter syndrome or mucopolysaccharidosis type II. The mutations that are tabulated include different deletions, splice-site and point mutations. From the group of 319 patients thus far studied by Southern analysis, 14 have a full deletion of the gene and 48 have a partial deletion or other gross rearrangements. All patients with full deletions or gross rearrangements have severe clinical presentations. Twenty-nine different “small” mutations have so far been characterised in a total of 32 patients. These include 4 nonsense and 13 missense mutations, 7 different small deletions from 1 to 3 bp, with most leading to a frameshift and premature chain termination, and 5 different splice-site mutations also leading to small insertions or deletions in the mRNA. A 60 bp deletion, that results from a new donor splice-site, has been observed in five unrelated patients with relatively mild clinical phenotypes. This information will not only be useful for MPS II patient and carrier diagnosis, but also will aid in the understanding of the structure and function of iduronate-2-sulphatase, and possibly in correlating genotype with phenotype. © 1993 Wiley-Liss, Inc.     

Angiotensin II maintains the structure and function of glomerular mesangium via type 1a receptor

 The angiotensin II type 1a (AT1a) receptor is the major receptor effecting the multiple actions of angiotensin II on the cardiovascular system. It is expressed abundantly in the glomerular mesangial cells of the kidney. We investigated glomerular changes in null mutant mice minus the AT1a receptor gene to gain an understanding of the in vivo action of angiotensin II via AT1a on the mesangium. Morphological observations and morphometric analysis revealed that the glomerular volume was greatly increased owing to the expansion of the mesangial area, which contained fluid-filled spaces with a small amount of fibrillar components. The mesangial cells lost contact with each other and with the perimesangial area of the glomerular basement membrane (GBM), so that the glomerular capillary neck was greatly widened. These findings suggest a defect of the anchoring function of mesangial cells resulting from some abnormality in mesangial matrix formation. We conclude that angiotensin II has an important role in the structural and functional maintenance of the mesangium via the AT1a receptor, especially by reinforcing the connection between mesangial cells and GBM via the mesangial matrix. Received: 11 December 1997 / Accepted: 30 March 1998     

Gastric adenocarcinoma of the fundic gland type shares common genetic and phenotypic features with pyloric gland adenoma

Gastric adenocarcinoma of the fundic gland type (GAFG) and pyloric gland adenoma (PGA) have recently been recognized as rare types of neoplasia. We performed comparative immunohistochemical and genetic analyses of 3 GAFGs and 12 PGAs. All of the 3 GAFGs were diffusely positive for pepsinogen‐I, MIST1 and MUC6, indicating the predominantly chief cell/mucous neck cell differentiation of these tumors. A small number of H.K‐ATPase‐positive parietal cells were also scattered. PGAs invariably exhibited diffuse MUC6 and TFF2 expression, consistent with the pyloric gland differentiation of these tumors. Ten of the 12 PGAs also unexpectedly exhibited focal expression of pepsinogen‐I and MIST1, suggesting that PGAs often show focal chief cell differentiation and phenotypically resemble mucous neck cells rather than pyloric glands. The mutation analyses revealed activating GNAS mutations, which have been reported to be frequently detected in PGAs, in two of the GAFGs. While GAFGs and PGAs are morphologically distinct lesions, our observations showed their partially overlapping immunohistochemical profiles and shared presence of GNAS mutations, in addition to their common occurrence in the fundic gland mucosa. Based on these observations, we suggest that both GAFGs and PGAs are closely related lesions characterized by a mucous neck cell/chief cell lineage phenotype.     

Microcephalic osteodysplastic primordial dwarfism type II and pachygyria: Morphometric analysis in a 2‐year‐old girl

Microcephalic osteodysplastic primordial dwarfism (MOPD) type II is a rare disorder characterized by skeletal dysplasia, severe proportionate short stature, insulin resistance and cerebrovascular abnormalities including cerebral aneurysms and moyamoya disease. MOPD type II is caused by mutations in the pericentrin (PCNT) gene, which encodes a protein involved in centrosomes function. We report a 2 year old girl affected by MOPD type II caused by two compound heterozygous loss‐of‐function variants in PCNT gene, of which one is a novel variant (c.5304delT; p.Gly1769AlafsTer34). The patient presented atypical brain magnetic resonance imaging (MRI) findings consistent with pachygyria. This was confirmed by morphometric analysis of cortical thickness (CT) and gyrification index by comparing MRI data of the patient with a group of eight age‐matched healthy controls. The statistical analysis revealed a significant and diffuse increase of CT with an anterior‐predominant pattern and diffuse reduced gyrification (p < .05). These findings provide new evidences to the emergent concept that malformations of cortical development are complex disorders and that new genetic findings contribute to the fading of classification borders.     

Distal‐type bronchiolar adenoma of the lung expressing p16INK4a – morphologic,immunohistochemical, ultrastructural and genomic analysis – report of a case and review of the literature

Bronchiolar adenoma (BA) of the lung is a rare benign neoplasm. Because of a chest abnormal shadow indicated by health checkup, a 77‐year‐old female nonsmoker underwent computed tomography, revealing an 8 mm ground glass nodule in the peripheral field of the right lower lobe. Wedge resection of the nodule was performed, with a frozen diagnosis of primary lung adenocarcinoma. The localized, 8 × 4 × 3 mm‐sized, jelly‐like mass microscopically revealed a lepidic‐growing lesion composed of ciliated columnar cells, mucous cells and basal cells surrounded by mucin pool. Neither nuclear atypia nor mitotic activity was noted. Immunohistochemically, the ciliated, mucous and basal cells were positive for TTF‐1 and p16^INK4a. Mucous cells were positive for napsin A and focally expressed MUC5AC. MUC6 was negative. Basal cells were positive for CK5/6, p40, p63 and podoplanin. Human papillomavirus genome was undetectable by in situ hybridization. Ultrastructurally, the bronchiolar epithelial tubules consisted of two layers, the inner nonciliated microvillous cells and the outer basal‐like cells, and some of the inner cells were filled with mucin granules in cytoplasm. Molecular analysis of the tumor failed to show driver mutations. The final diagnosis was distal‐type BA. The postoperative course was uneventful for 6 months.     

Atypical skeletal changes in otopalatodigital syndrome type II: Phenotypic overlap among otopalatodigital syndrome type II,boomerang dysplasia,atelosteogenesis type I and type III,and lethal male phenotype of Melnick-Needles syndrome

We report on 2 cases of otopalatodigital syndrome type II (OPD II) with atypical skeletal changes, overlapping those of boomerang dysplasia, atelosteogenesis type I (AO I) and type III (AO III), and the lethal male phenotype of Melnick-Needles syndrome. One patient exhibited strikingly broad, bowed femora, which resembled those of boomerang dysplasia. The other patient possessed conspicuous undertubulation of the long bones, defective ossification of the spine, and severe undermineralization of the calvaria, which may have caused diagnostic confusion with AO I, AO III, and the lethal male phenotype of Melnick-Needles syndrome. OPD II is transmitted as an X-linked recessive trait, whereas AO I, AO III, and boomerang dysplasia are considered to result from a new dominant mutation, and Melnick-Needles syndrome is inherited as an X-linked dominant trait. Accordingly, differential diagnosis is mandatory to provide the affected families with adequate genetic counseling. Awareness of these skeletal changes in OPD II will prevent the misdiagnosis of this entity as other disorders. Furthermore, the phenotypic overlap among these disorders may expand the entities that constitute the OPD-Larsen dysplasia family proposed by Spranger [1985]. Am. J. Med. Genet. 73:132–138, 1997. © 1997 Wiley-Liss, Inc.     

An electron microscopical study of the influence of different glycosaminoglycans on the fibrillogenesis of collagen type I and II in vitro

Summary Proteoglycans (PG) and glycosaminoglycans (GAG) bind to collagen, and thus influence fibril formation. Polysaccharides interfere with the aggregation of collagen molecules and affect pattern formation.The morphological structure of type I and type II collagen was studied after adding different GAG to collagen solutions in test tubes in vitro. Electron microscopical investigations suggest that sulfated GAG change the aggregation behaviour of collagen molecules. Thus, the cross-striation pattern is changed. This effect seems to be based on the degree of sulfatation and not on the molecular weight of the GAG. Furthermore, GAG appear to have a stabilizing influence on the in vitro fibril formation.