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.     

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.     

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.     

bcl-2 and p53 immunophenotypes in pre-invasive, early and advanced oesophageal squamous cancer

 

Aims:

An inverse correlation between bcl-2 and p53 expression has been reported in several types of epithelial tumour. The role of bcl-2 and p53 in the development of oesophageal squamous carcinoma has yet to be established. The expression of bcl-2 and p53 proteins has been evaluated in the multistage oesophageal tumorigenesis, which progresses from normal mucosa to dysplasia (squamous intraepithelial lesion, SIL), to invasive early and advanced oesophageal squamous cancer.  

Methods and results:

Sixty-four cases of squamous oesophageal cancer, coexisting with SIL in 18 cases, were immunohistochemically analysed for any overexpression of bcl-2 and p53 proteins. Any association of bcl-2 and p53 protein expression with patient survival was also analysed. We observed bcl-2 expression that decreased significantly during the progression of oesophageal carcinogenesis. A decreasing frequency in the expression of bcl-2 in advanced oesophageal squamous cancer coincided with frequent p53 overexpression. bcl-2 expression was correlated with patient survival by univariate analysis. The association disappeared after adjusting for tumour stage. p53 overexpression showed no association with patient survival by either univariate or multivariate analysis.  

Conclusions:

The down-regulation of bcl-2 and up-regulation of p53 in advanced oesophageal squamous cancer suggest that bcl-2 and p53 proteins may interact in the progression of oesophageal squamous cancer.     

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.     

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.     

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.     

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.     

Expression of c-Met correlates with grade of malignancy in human astrocytic tumours: an immunohistochemical study

 

Aims:

Recent studies suggest the involvement of hepatocyte growth factor/scatter factor (HGF/SF) in glioma cell invasion and tumour progression. We investigated the distribution and rate of tumour cells that express c-Met protein, which is the cell-surface receptor for HGF/SF, in astrocytic tumours. The type of cells that express c-Met in tumour tissues was also identified.  

Methods and results:

c-Met expression was screened immunohistochemically in a total of 43 astrocytic tumours, including 14 low-grade astrocytomas (A), 13 anaplastic astrocytomas (AA) and 16 glioblastoma multiforme (GBM). c-Met reactivity was demonstrated predominantly in the cytoplasm of tumour cells. Bizarre large tumour cells tended to stain intensely. Higher c-Met expression levels (≥ 2 +, more than 25% cells were positive) were noted in 21.4% of (A) vs. 53.8% in (AA) and 87.5% in (GBM) ( P  < 0.001), indicating a clear relationship between c-Met protein staining and higher grade astrocytic tumours. Moreover, c-Met immunoreactivity was also shown in tumour microvasculature, reactive astrocytes, and neurones in the cortex infiltrated by glioma cells. In 85.7% of cases containing infiltrated cortex, neurones were positive vs. no neurones in non-neoplastic regions ( P  < 0.002).  

Conclusions:

This evidence suggests that c-Met expression in the brain could be associated with astrocytoma progression and also reactive process. Immunohistochemical determination of c-Met-expressing cell types helps to understand possible roles of c-Met in tumour tissues.     

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.     

Reproducible and highly sensitive detection of the broad spectrum epithelial marker keratin 19 in routine cancer diagnosis

 

Aims:

In this study the recently developed keratin 19 antibody RCK108 is biochemically and immunohistochemically characterized. Its applicability as a keratin marker in routinely processed histological tissue specimens is assessed.  

Methods and results:

The keratin 19 antibody RCK108 antibody was tested on normal and malignant routinely formalin-fixed, paraffin-embedded tissue specimens. It stains most, although not all, glandular epithelia and showed (focal) reactivity in the basal cell compartment of stratified epithelia. It was found to react with most epithelial tumours, including adenocarcinomas, squamous cell carcinomas and endocrine tumours of various origins.  

Conclusions:

Its reproducible and highly sensitive staining characteristics make RCK108 a useful antibody to be applied as a broad epithelial marker for carcinoma detection in routinely processed paraffin sections. As such, RCK108 is a specific reagent for practically all epithelial tumours. A few types of epithelial malignancies, known not to contain keratin 19, were negative for RCK108. Therefore the antibody is also useful in some narrow differential diagnostic considerations such as cholangiocellular carcinoma (RCK108 positive) vs. hepatocellular carcinoma (RCK108 negative). Another important feature of this antibody is that it shows very little reactivity in mesenchymal tissues, or mesenchymally derived tumours, as is frequently described for other keratin antibodies. A few leiomyosarcomas showed sporadic reactivity.     

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.     

p53 tumour suppressor gene protein expression in early and advanced gallbladder carcinoma

 

Aims:

Gallbladder carcinoma is one of the most frequent malignant tumours occurring in Chile and the mortality rate in both sexes ranks among one of the highest in the world. Mutation of p53 tumour suppressor gene has been demonstrated in many tumours. Our aim was to determine protein expression of p53 gene in early and advanced gallbladder carcinoma.  

Methods and results:

Protein expression of gene p53 was studied by immunohistochemical means in 191 gallbladder carcinomas (157 primary tumours, 34 metastases) and 25 controls. In 86 out of 191 cases (45%), protein expression of gene p53 was observed. Differences related to sex, age, or race were not observed. All gallbladder controls were negative. Twenty-five per cent of well-differentiated tumours were p53 positive, while moderate or poorly differentiated carcinomas reached 50% ( P  = 0.04). p53 expression was observed in 23.5% of early carcinomas and in 48.2% of advanced carcinomas ( P  = 0.01). No differences between primary tumours and metastasis were demonstrated.  

Conclusions:

Protein expression of p53 tumour suppressor gene is observed in 45% of gallbladder carcinomas. The absence of expression in controls and in normal mucosa adjacent to tumours suggests its utility in differentiating atypical gallbladder epithelia from neoplastic lesions.     

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.     

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.     

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.     

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.     

Loss of basement membrane components laminin and type IV collagen parallels the progression of oral epithelial neoplasia

Aims : To determine the immunohistochemical localization of basement membrane components laminin and type IV collagen in premalignant and malignant lesions of the oral epithelium.  

Methods and results

Formalin-fixed tissue sections of 12 epithelial hyperplasias with no dysplasia and 30 dysplasias, clinically diagnosed as leukoplakia and/or erythroplakia, as well as 50 invasive squamous cell carcinomas, were stained with mouse monoclonal antibodies to human laminin and type IV collagen. Statistical analysis showed that there was a linear trend for discontinuous distribution of laminin from epithelial hyperplasia to epithelial dysplasia and invasive squamous cell carcinoma ( P  < 0.001). Laminin staining showed a linear trend for discontinuity with increasing grade of dysplasia ( P  < 0.05) and was more frequently discontinuous in areas of deep tumour invasion than in central or superficial areas ( P  < 0.05). Brush-shaped thickening and reduplication of the basement membrane were also identified.  

Conclusions

Alterations in the distribution of laminin and type IV collagen in oral premalignant and malignant lesions indicate that the loss of continuity of the subepithelial basement membrane parallels the progression of the neoplastic transformation process in oral epithelium.     

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.     

Mucoepidermoid carcinoma arising in Warthin's tumour of the parotid gland: report of two cases with histopathological, ultrastructural and immunohistochemical studies

Aims : Malignant transformation of Warthin's tumour (WT) is a rare event. We present two cases of mucoepidermoid carcinoma (MEC) arising in WT in the parotid gland.  

Methods and results

Two cases of MEC arising in WT, which were found in 185 cases of WT of the parotid gland, were investigated by light and electron microscopy, and immunohistochemistry. Both cases had largely similar macroscopic and histological features with some differences. Histologically, the tumours consisted mainly of WT with multilayered hyperplastic arrangements of oncocytic cells and focal squamous and goblet cell metaplasia. In the same tumour mass, however, the features of MEC were observed with invasion to adjacent adipose tissue. A transitional zone between WT and MEC was evident. Both patients were alive and well without evidence of recurrence 30 and 34 months after surgery, respectively. Electron microscopy revealed that cyst lining epithelial cells in WTs had abundant mitochondria whereas some of the MEC cells contained numerous tonofilaments and mucinous granules. Immunohistochemically, oncocytic cells of WTs were strongly positive for mitochondria and Salyl-Tn was extensively stained in MECs. The labelling index for Ki67 was obviously higher in the carcinoma cells than the epithelial cells of WT.  

Conclusions

Our cases confirmed the possibility of malignant transformation of the epithelial component in WT to MEC.