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.     

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.     

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.     

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.     

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.     

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.     

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.     

Thyroid carcinoma associated with familial adenomatous polyposis

 

Aims:

Thyroid carcinoma is an extracolonic manifestation that is present in about 1% to 2% of patients with familial adenomatous polyposis (FAP). Less than 100 cases have been reported in detail. We have investigated the suggestion that FAP associated thyroid carcinoma is significantly different morphologically from both papillary and follicular types and can be considered as a separate entity.  

Methods and results:

Specimens from three patients with FAP associated thyroid tumours, all but one having single nodules, have been analysed. All three patients belonged to an extended kindred (23 siblings in four generations) who had genetic analysis and intensive screening for thyroid nodules. Seven patients had the same APC mutation at codon 1061. Pathological examination revealed a typical papillary carcinoma, encapsulated variant, in all patients, with follicular areas in one case. All thyroid specimens, in addition to histological and immunohistological examinations, were also specifically studied for activation of the RET-PTC oncogene, that seems to be restricted to papillary thyroid carcinoma. Two of the three patients had RET-PTC activation (PTC₁ isoform).  

Conclusions:

The findings suggest that the tumours were certainly papillary, at least in the present kindred. Further studies in different families are required for a better understanding of this peculiar tumour and of its biological behaviour.     

Immunophenotypic heterogeneity of hyalinizing trabecular tumours of the thyroid

 

Aims:

We studied 12 cases of hyalinizing trabecular tumour of the thyroid gland (HTT) with the aim of reviewing the cytological, histological and immunophenotypic features and of investigating the relationships of HTT with other thyroid neoplasms.  

Methods and results:

Eleven patients were female and one male, aged 8–74 years (median 58). Ten cases had a benign behaviour, while two cases were locally aggressive. Of the latter, one developed distant metastases and the other is a recent case. All patients are alive 6–311 months after diagnosis. Cytologically, HTT was characterized by hypercellular smears with aggregates of roundish cells having features of papillary carcinoma (nuclear grooves, vacuoles) and fragments of fibrous tissue. Histologically, prominent nesting, trabecular growth patterns and a hyaline stroma (partly positive for laminin and collagen type IV) were found. One case was associated with a papillary microcarcinoma. Two additional cases had extensive areas of papillary carcinoma. In one of these, hyalinized papillary stalks were observed. All tumours contained thyroglobulin but not calcitonin. High molecular weight cytokeratin (a marker of papillary carcinoma) was focally positive in 4/12 cases only and thyroperoxidase (a marker of follicular adenomas, but not of papillary carcinoma) was found in 3/12 cases.  

Conclusions:

The immunophenotypic profile and the morphological features suggest that HTTs are an heterogeneous group of tumours, some of them probably representing variants of papillary carcinoma with hyalinized stroma.     

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.     

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.     

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.     

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.     

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.     

Granular cell dermatofibroma

 

Aims:

To describe a series of five granular cell dermatofibromas as an unusual and rare manifestation of fibrohistiocytic tissue response.  

Methods and results:

Five granular cell dermatofibromas were collected out of 136 tumours filed as granular cell tumours. Clinically, all lesions occurred on the shoulder or back of middle-aged adults (two women, three men), mostly with the clinical diagnosis of a fibrohistiocytic lesion. Histology revealed well-circumscribed, dermal to subcutaneous lesions dominated by periodic acid–Schiff (PAS) positive, granular cells. Acanthosis above, as well as storiform arrangement of spindle cells, sclerotic collagen and some interspersed lymphohistiocytic infiltrate at the periphery of the lesion, indicated the fibrohistiocytic origin. Lesions showed prominent reactivity with NK1C3 (CD57), as well as for macrophage markers KiM1p and KP1 (CD68). In contrast to classic Schwannian/neurogenic granular cell tumours, granular cell dermatofibromas were S100 protein negative, but showed variable reactivity for factor XIIIa (10–50%) in 4/5, for smooth muscle specific actin (10–50%) in 2/5 and with E9 (10–30%) in 3/5 lesions. Electron microscopy in one case revealed large pools of phago-lysosomes and variably sized glycogen granules in granular cells.  

Conclusion:

Our series delineates granular cell dermatofibroma as a distinct clinicopathological variant of fibrohistiocytic tissue response which needs to be distinguished from other tumours with granular cell features.     

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.     

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.     

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.     

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.