Systemic-to-pulmonary vascular malformation of lung visualized by computer-assisted 3-D reconstruction

 

Aims:

While a growing number of cases with pulmonary arteriovenous malformation (PAVM) have been reported, detailed analysis has yet to be found on the relation of abnormal vessels with the whole lung vasculature and airways. To gain more insight into the structure–function interrelation of this disease, we attempted to visualize the vessels in and around the arteriovenous malformation, resorting to computer-aided 3-D reconstruction.  

Methods and results:

The material was the upper lobe of the right lung from a 44-year-old man resected for recurrent haemoptysis. On pre-surgical selective angiography, an arteriovenous communication was suggested to exist between a tributary of the right 3rd intercostal artery and pulmonary vein. Semi-serial sections were prepared from the material and submitted to 3-D reconstruction of blood vessels and airways. In 3-D images, branches of the 3rd intercostal artery proved to be forming a plexus of abnormally dilated, thin-walled vessels in the subepithelial layer of a membranous bronchiole, a situation clearly explaining the mechanism of haemoptysis. There was no capillary bed interventing between the afferent arteries and draining vessels leading to the pulmonary vein.  

Conclusions:

This presents the first overall visualization of PAVM, allowing comparison of 2-D microscopy with the corresponding 3-D morphology.     

Mammary epidermoid inclusion cysts after wide-core needle biopsies

 

Aims:

To investigate the prevalence of squamous epidermoid inclusion cysts after wide-core needle biopsy.  

Methods and results:

Epidermoid inclusion cysts were found in five of 17 surgical excisions (29%) after preliminary wide-core needle biopsies in a 7-month period. Thereafter they were not seen in 26 subsequent postwide-core surgical excisions in a period of 6 months.  

Conclusions:

The cysts appear to be an iatrogenic complication of wide-core biopsy, and need morphological recognition in order to avoid confusion with spontaneous squamous metaplasia of benign or malignant breast epithelium. Longer term implications are unknown.     

Identification of oncocytic lesions of salivary glands by anti-mitochondrial immunohistochemistry

 

Aims:

To evaluate the immunohistochemistry using an anti-mitochondria antibody in the investigation of various oncocytic lesions of the salivary glands.  

Methods and results:

Ten cases of adenolymphoma (Warthin's tumour) and one case each of benign oncocytoma and oncocytic carcinoma of the salivary glands were examined. Normal salivary glands were also tested. They were investigated immunohistochemically using mouse monoclonal antibody against human mitochondria. In normal salivary glands, epithelial cells of the striated ducts showed a thick linear immunoreactivity, which corresponded well to the intracytoplasmic distribution pattern of mitochondria. In addition, a small number of swollen epithelial cells showing an intense, finely granular immunoreactivity in the cytoplasm were scattered in the ductal system and acini ('oncocytic metaplasia'). Almost all neoplastic cells involved in adenolymphoma, benign oncocytoma, and oncocytic carcinoma showed an intense, finely granular immunoreactivity in the cytoplasm.  

Conclusions:

Immunohistochemistry using the anti-mitochondria antibody proved to be a highly sensitive and specific method for light microscopic identification of mitochondria and superior to routine H & E or PTAH stain especially in the detection of isolated oncocytic cells.     

Multinucleated stromal giant cells of testis

 

Aims:

This study documents the frequency of multinucleated stromal giant cells within the interstitium of the testis and looks for possible aetiological reasons for this occurrence.  

Materials and methods:

We examined sections of testes from 150 unselected autopsy cases finding stromal giant cells in 43%. An aetiological association between the occurrence of multinucleated stromal giant cells in this site and hormonal or other pathogenetic influences could not be established.  

Conclusions:

In many instances, this occurrence appears to be an age related phenomenon.     

Intravascular lymphomatosis: a clinicopathological study of two cases presenting as an interstitial lung disease

 

Aims:

Intravascular lymphomatosis is an uncommon type of non-Hodgkin's lymphoma characterized by intravascular proliferation of neoplastic lymphoid cells. Although the tumour is basically a systemic disease, eventually involving multiple organs, primary presentation in the lung is rare.  

Methods and results:

We describe the clinicopathological features of two patients with intravascular lymphomatosis presenting in the lung. One patient complained of fever, headache and chest pain; the other, of dyspnoea on exertion and headache. Both patients showed reticulonodular density on chest radiography and decreased diffusion capacity. Lung biopsy showed features characteristic of intravascular lymphomatosis. Malignant lymphoid cells were CD30 positive T-cells of anaplastic large cell type in one patient and B-cells of large cell type in the other. There was a poor response to chemotherapy and both patients died of the disease within 3 months of diagnosis.  

Conclusions:

These cases and 10 previous reports illustrate the need to include intravascular lymphomatosis in the differential diagnosis of interstitial lung disease.     

Stereological estimates of the nuclear/cytoplasmic ratio and star volume on fibreoptic biopsies are of prognostic value for survival in a preliminary study of advanced squamous cell carcinoma of the lung

 

Aims:

This study evaluated the role of morphometric and clinical parameters in establishing the prognosis of patients submitted to radiotherapy for advanced squamous cell carcinoma of the lung.  

Methods and results:

Morphometric studies were performed by point counting techniques. Forty patients were included in this study. Group 1 patients ( n  = 22) were those with survival equal to or less than 6 months; group 2 ( n  = 10) patients had a survival of 7 to 12 months; and group 3 ( n  = 8) included patients with survival greater than 12 months. To characterize these three groups of patients, models combining categorical and continuous variables were constructed by means of discriminant analysis. Weight loss, histological grade, nuclear/cytoplasmic ratio and star volume of the nuclei were selected during the backward procedure as relevant variables to characterize the three groups of patients. The overall sensitivity of the model was 90%.  

Conclusions:

Our results indicate that histopathological data may help to predict prognosis in patients with advanced squamous cell lung carcinoma, and encourage the use of morphometric procedures in histopathological analysis of this type of lung tumour.     

Rapid verification of the identity of questionable specimens using immunohistochemistry with monoclonal antibodies directed against HLA-class I antigens

 

Aims:

A case report is presented in which an unexpected pathological diagnosis raised the possibility that biopsies of two patients were mixed-up. Since these biopsies were obtained from kidney transplant patients, the HLA-typings of both patients were known.  

Methods and results:

We developed an immunohistochemical method using HLA-class I specific monoclonal antibodies to recognize the donor and recipient antigens in these biopsies. Using this method we could confirm the identity of the patients of whom the biopsies had been taken.  

Conclusions:

This method, which uses the highly polymorphic HLA-system, is potentially useful for rapid and easy verification of the identity of specimens if a mix-up is suspected.     

Gastrointestinal tumour masses due to multiple myeloma: a pathological mimic of malignant lymphoma

 

Aims:

To describe and evaluate two cases of gastrointestinal involvement by multiple myeloma.  

Methods and results:

Clinical details were obtained from patients records and routine histopathological sections were correlated with haematological and immunohistochemical investigations. As shown in the accompanying illustrations, myeloma manifests as large, atypical, non-cohesive cells which may mimic high-grade lymphoma.  

Conclusions:

Extraskeletal spread of multiple myeloma occurs more frequently than is currently recognized, but clinical involvement of gut is rarely reported. Gut involvement may occur soon after initial diagnosis of myeloma and may be of serious clinical consequence. Histologically, it may mimic high-grade lymphoma. Failure to recognize myelomatous involvement of gut may result in inappropriate surgery or oncological therapy.     

Carcinosarcoma of the oesophagus showing neuroendocrine, squamous and glandular differentiation

 

Aim:

A case of oesophageal carcinosarcoma occurring in a previously fit, 64-year-old man is reported.  

Case summary:

The carcinomatous component displayed neuroendocrine, squamous and glandular differentiation; the sarcomatous component showed no specific features of differentiation. In-situ squamous carcinoma was present in the adjacent squamous mucosa. The most superficial part of the invasive tumour consisted of carcinosarcoma with a predominant neuroendocrine epithelial component. Squamous carcinoma without an accompanying sarcomatous component occupied most of the deeper part of the tumour, suggesting outgrowth of this tumour type by a selective growth advantage.  

Conclusion:

We speculate that further tumour growth might have led to complete replacement of the tumour by pure squamous carcinoma, and that other advanced oesophageal squamous carcinomas might have had their origin in a short-lived carcinosarcomatous phase.     

Pancreatic tissue in a lateral cervical cyst attached to the thyroid gland—a presumed foregut remnant

 

Aim:

To report the previously undescribed occurrence of a lateral neck cyst, attached to the thyroid gland, containing pancreatic tissue.  

Methods and results:

A 41-year-old man presented with a recurrent cystic lesion of the thyroid. At thyroidectomy cystic masses containing mucinous material were present in the neck, and there was a nodular lesion attached to the lower pole of the thyroid. Histological examination of the latter lesion revealed an epithelial lined cyst, with pancreatic tissue (exocrine and endocrine) in addition to fat, fibrous tissue, muscle and cartilage in the wall.  

Conclusions:

The possible origin of this structure is discussed, with the conclusion being that it most likely represents a foregut remnant.     

Adenomyoepithelioma of the skin: a case report with immunohistochemical and ultrastructural observations

 

Aims:

The histological, immunohistochemical and electron microscopic features of a primary adenomyoepithelioma of skin, a rare sweat gland tumour, are reported.  

Methods and results:

The tumour occurred on the back of a 92-year-old woman. It was composed of well-formed tubules lined by epithelial cells surrounded by clear or spindled myoepithelial cells. Immunohistochemically, the epithelial cells exhibited strong cytokeratin (CAM5.2) and weak carcinoembryonic antigen positivity. The myoepithelial cells showed diffuse positivity for smooth muscle actin and focal positivity for S100 protein. Ultrastructurally, the myoepithelial cells contained myofilaments with focal densities and hemi-desmosomes. They were limited by well-formed basal lamina. The tumour was associated with a small eccrine spiradenoma.  

Conclusion:

We predict that the tumour will behave in a benign fashion. There is no evidence of recurrence or metastasis 28 months later.     

Osteoid and bone formation in a nasal mucosal melanoma and its metastasis

 

Aims:

To present a literature review and a case history concerning bone and osteoid formation by a metastasizing (mucosal) melanoma.  

Case details:

Osteocartilaginous differentiation and production of osteocartilaginous structures in malignant melanoma have been described only in 12 previous cases (osteoid in 11, bone in four), all of which involved dermal melanomas. Five of these melanomas were recurrent and one was associated with neurofibromatosis. The case report concerns a 75-year-old man with a nasal mucosal melanoma which was treated surgically. One year later, the patient developed a local recurrence and a cervical lymph node metastasis. Both the recurrent tumour and the metastasis showed clear evidence of bone and osteoid formation.  

Conclusions:

This case is the first report in the literature, clearly demonstrating bone and osteoid formation by a mucosal melanoma, not only at the primary site, but even more convincingly in a cervical lymph node metastasis.     

Expression of stratified epithelial-type cytokeratins in hyalinizing trabecular adenomas supports their relationship with papillary carcinomas of the thyroid

 

Aim:

To evaluate the cytokeratin pattern of expression of hyalinizing trabecular adenomas and to verify whether or not these tumours, that share morphological features with papillary carcinomas, present the stratified epithelial-type cytokeratins commonly found in ordinary papillary carcinomas.  

Methods and results:

This study consisted of the immunohistochemical detection of simple and stratified epithelial type cytokeratin filaments in a series of six hyalinizing trabecular adenomas, three papillary carcinomas with a trabecular growth pattern and two carcinomas combining hyalinizing trabecular and papillary patterns. Simple epithelial-type cytokeratins 7, 8, 18 and 19 were found in every case. Expression of the stratified epithelial-type cytokeratins 1, 5/6 and/or 13 was detected in four hyalinizing trabecular adenomas.  

Conclusion:

Based on this, as well as on the cytological features and on the frequent co-occurrence of hyalinizing trabecular adenoma and papillary carcinoma, we suggest that the former lesion may be considered a peculiar encapsulated variant of papillary carcinoma.     

Erythrophagocytic tumour cells in melanoma and squamous cell carcinoma of the skin

 

Aims:

Erythrophagocytosis is a characteristic feature of tumour cells in malignant histiocytosis, some leukaemias, lymphomas, and also reactive histiocytes in the haemophagocytic syndrome associated with a variety of infections and neoplasms. It has also been found exceptionally in metastatic malignant epithelial cells in bone marrow and lymph nodes. We present two cases, a cutaneous malignant melanoma and an acantholytic squamous cell carcinoma, in which erythrophagocytosis by tumour cells was demonstrable by both light and electron microscopy.  

Methods and results:

The melanocytic and squamous nature of these cells was supported by the immunohistochemical detection of HMB45, S100, and NKI-C3 in the former, and cytokeratin and EMA in the latter, and at ultrastructural level by the presence of melanosomes and tonofilaments, respectively.  

Conclusions:

This is, to our knowledge, the first documented report of erythrophagocytic tumour cells in human melanomas and primary carcinomas. Biological considerations apart, this unusual feature can prove to be of value to avoid a misdiagnosis of a variety of haematopoietic malignancies.     

Lesions of 13q may occur independently of deletion of 16q in spindle cell/pleomorphic lipomas

 

Aims:

Very recent multidisciplinary investigations have allowed for the definition among lipomas of a clinical and histological subtype called spindle cell and/or pleomorphic lipoma, possibly associated with partial monosomy 16 and anomalies of chromosome 13. In order to get nearer to the underlying critical molecular changes further multidisciplinary pathological and genetic research is indicated, to identify which chromosome(s) anomalies are crucial in the development of these tumours.  

Methods and results:

In an ongoing multidisciplinary study of lipomatous tumours, including clinical findings, morphology, histochemistry and cytogenetics, two instances were found of spindle cell lipoma with clonal chromosome changes. In both cases chromosome 13 was involved, whereas only one showed a partial monosomy 16.  

Conclusions:

Partial monosomy 16 is a characteristic lesion in spindle cell lipoma, usually associated with anomalies of chromosome 13. The present report confirming a previous single observation indicates, however, that lesions of 13 may occur independently from lesions of 16, suggesting different underlying molecular lesions in these otherwise very similar lipomas.     

Enteropathy-associated T-cell lymphomas have a cytotoxic T-cell phenotype

 

Aims:

Enteropathy-associated T-cell lymphoma (EATCL) is a rare complication of coeliac disease. We investigated whether EATCLs are the neoplastic counterparts of activated cytotoxic T-cells (CTLs).  

Methods and results:

Eight cases, clinically and histologically defined, were stained with monoclonal antibodies against components of the cytotoxic granules of CTLs, granzyme B and T-cell restricted intracellular antigen (TIA-1). It was found that all cases had a cytotoxic phenotype, i.e. expression of TIA-1 in most of the tumour cells, whereas granzyme B was found in six of eight cases, mostly in a smaller number of tumour cells compared to TIA-1. Since TIA-1 and granzyme B are expressed at different stages of activation of CTLs it is hypothesized that differences in expression between granzyme B and TIA-1 in EATCL represent different stages of activation in which the tumour cells are arrested. Clinically, seven of the eight patients died within 10 months after diagnosis of EATCL.  

Conclusions:

EATCL is a clinicopathological entity with a grim prognosis and with tumour cells representing a unique neoplastic equivalent of CTLs arrested in varying stages of activation.     

Large cell neuroendocrine carcinoma of the thymus

 

Aim:

We highlight the occurrence of an unusual neuroendocrine tumour, a large cell neuroendocrine carcinoma, arising from the thymus.  

Case details:

A 68-year-old man with a history of cigarette smoking had a large mediastinal tumour arising from the thymus removed. Two years later the tumour recurred; it was debulked surgically but the patient died 2 months later. Histological examination of both tumour specimens revealed a tumour with an endocrine pattern, composed of large pleomorphic cells with large nuclei and prominent nucleoli. The mitotic count ranged from 19 to 26 per 10 high-power fields and large tracks of coagulative tumour necrosis were present. The tumour cells were strongly positive for neuron-specific enolase (NSE), chromogranin, CAM5.2 and AE1/3, with cytoplasmic dot-like accentuation for the latter three markers. The tumour fulfilled the criteria for a diagnosis of large cell neuroendocrine carcinoma.  

Conclusions:

Large cell neuroendocrine carcinoma should be distinguished from atypical carcinoid and small cell carcinoma. It is a distinctive neuroendocrine malignancy with a prognosis between that of atypical carcinoid and small cell carcinoma, and needs to be treated aggressively.     

Apoptosis occurs more frequently in intraductal carcinoma than in infiltrating duct carcinoma of human breast cancer and correlates with altered p53 expression: detected by terminal-deoxynucleotidyl-transferase-mediated dUTP-FITC nick end labelling (TUNEL)

 

Aims:

We examined the relationship between apoptosis and three different major stages of human breast carcinoma: intraductal carcinoma (DCIS), infiltrating duct carcinoma (IDC) and metastatic carcinoma in lymph nodes. We also determined the correlation between apoptosis and oestrogen receptor (ER), progesterone receptor (PR) and p53.  

Methods and results:

The study investigates the extent of apoptosis in 63 breast carcinomas by in-situ end-labelling, in formalin-fixed, paraffin-processed tissue sections. The 63 breast carcinomas, included 22 DCISs, 26 IDCs, three infiltrating lobular carcinomas (ILC) and 12 metastatic lymph nodes. The apoptotic labelling index was higher in DCIS than IDC and metastatic carcinoma ( P  < 0.001, P  < 0.007, respectively). By immunohistochemistry, we also analysed p53, ER and PR. Apoptosis correlated significantly with p53 ( r  = 0.748, P  = 0.0004) in IDC. Also, ER correlated significantly with PR ( r  = 0.629, P  = 0.00001). No apparent correlation was found between the apoptosis and ER or PR.  

Conclusion:

Our data suggest that not only does apoptosis differ between intraductal carcinoma and infiltrating carcinoma but also it might be regulated by altered p53 expression.     

Retrieved endogenous biotin: a novel marker and a potential pitfall in diagnostic immunohistochemistry

 

Aim:

Antigen retrieval (AR) procedures are based on the effect of heating (by either microwave or pressure cooking treatments) on routinely fixed and paraffin embedded tissues. We observed that AR procedures restore the reactivity of endogenous biotin (EB) and report on the distribution of EB following AR in a series of routinely fixed and embedded tissues.  

Methods and results:

Following pressure cooking or microwave treatments, a simple streptavidin–peroxidase staining revealed retrieved endogenous biotin (REB) in normal tissues (such as liver, kidney and adrenal cortex), in oxyphylic cells and in some tumours, especially in carcinomas of the kidney and of the adrenal cortex. In formalin-fixed (but not in alcohol-fixed) tissue sections, the heating procedures caused an intense and finely granular cytoplasmic reaction, following a routine streptavidin-conjugated peroxidase treatment. The staining was prevented by blocking of EB by a sequential avidin–biotin treatment.  

Conclusions:

Retrieval of EB reactivity can cause pitfalls in diagnostic immunohistochemistry but, alternatively, it might also constitute a useful and novel diagnostic marker.     

Down-regulation of CD95 (Fas/Apo-1) in the epithelia of adenovirus-infected appendices

 

Aims:

Adenoviral inclusions are commonly seen in appendices from infants with intussusception. They are associated with focal epithelial budding and less frequently with epithelial shedding. These morphological changes could depend on the opposing effects of adenoviral gene products on CD95-mediated apoptosis.  

Methods and results:

Appendices from intussusceptions with viral inclusions ( n  = 4) and normal appendices ( n  = 10) were studied by immunochemistry with anti-adenovirus, anti-CD95 and anti-HLA-DR antibodies. Apoptosis was studied by the TUNEL method. The mucosa of normal appendices contained no adenoviral protein. CD95 was present in all epithelial cells except Paneth cells. HLA-DR was absent in epithelial cells and apoptosis was seen only in germinal centres and in a few surface epithelial cells. The epithelium of appendices from intussusceptions contained nuclear inclusions labelled with anti-adenovirus antibody, always found in the epithelial buds. The epithelial CD95 pattern was drastically altered in adenovirus-infected appendices. CD95 was absent from the budding foci. In these foci, HLA-DR was overexpressed. There was also increased epithelial apoptosis in areas remote from those lacking CD95 antigen.  

Conclusions:

The appearance of epithelial budding or shedding in appendices from intussusception could be due to focal in situ differences in the expression of adenoviral genes.