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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

Prognostic value of high serum levels of CA-125 in malignant secretory peritoneal mesotheliomas affecting young women. A case report with differential diagnosis and review of the literature

 

Aims:

Very few cases of diffuse, malignant, peritoneal mesothelioma have been reported in young women. Distinction between peritoneal mesothelioma and serous epithelial tumours, including papillary serous carcinomas and borderline serous tumours, can be difficult. Differential diagnosis based on clinical appearance and imaging techniques is broad and inconclusive, thus the diagnosis must be confirmed by histological examination. Because the vast majority of tumours involving the peritoneal and serosal surfaces are due to primary or metastatic serous epithelial tumours, there is a tendency on the part of pathologists to disregard the possibility of mesothelioma when examining a biopsy or excision specimen. This is especially likely to occur when mesothelioma is associated with highly elevated serum levels of CA-125, which is the typical tumoral marker of epithelial serous tumours from the ovary. The association between peritoneal mesothelioma and high serum levels of CA-125 has been reported in the literature only in two cases.  

Case details:

In order to avoid a misdiagnosis of this neoplasm we describe a new case of peritoneal mesothelioma in an 18-year-old woman with high serum levels of CA-125.  

Conclusions:

Besides its clinicopathological characteristics and its histological, immunohistochemical and ultrastructural features, we describe its biological behaviour, which seems to be worst when CA-125 levels are high.     

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.     

Intestinal metaplasia subtyping: evaluation of Gomori's aldehyde fuchsin for routine diagnostic use

 

Aims:

Intestinal metaplasia (IM) has been implicated in the pathogenesis of gastro-oesophageal carcinoma, but because of its common occurrence, its specificity for use in cancer surveillance is low. IM subtypes characterized by mucin phenotype have been studied to try and improve specificity.  

Methods and results:

On balance, type III IM seems the most promising for use in gastric cancer surveillance. The situation is problematic at the gastro-oesophageal junction where the normal occurrence of acidic mucins raises doubt on the value of subtyping. High iron diamine–Alcian blue combination (HID-AB) is commonly used for IM subtyping, but its potential toxicity and long staining period (up to 24 hours) precludes widespread clinical use. This study has compared the sulphomucin staining ability of Gomori's aldehyde fuchsin–Alcian blue combination (GAF-AB) against HID-AB for identifying and subtyping IM in gastric and oesophageal biopsies.  

Conclusions:

Compared to HID-AB, a sensitivity of 85%, a specificity of 100% and a staining time of less than 30 minutes, shows this stain to be a simple and effective technique for identifying and subtyping IM in routine laboratories.     

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.     

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.     

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.     

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.