Types and patterns of response in the larynx following inhalation

The laryngeal mucosa responds to insult similarly to other epithelial tissues but the response depends on location within the larynx since important anatomic differences exist, even within rodent species. Although dogs and nonhuman primates are also utilized for inhalation toxicology studies, little published information is available regarding sites of injury from inhaled toxicants in these species. Accurate and consistent fixation, trimming, and microtomy of laryngeal sections allow the pathologist to compare the morphology of laryngeal mucosa from exposed and control animals and detect and interpret subtle differences resulting from inhalation exposure. There are anatomic landmarks that are keys to providing consistent sections through important areas of the laryngeal mucosa. Repeated inhalation of toxic concentrations of chemicals, drugs, or environmental contaminants induces a wide range of responses, depending on the physical properties and concentration of the toxic substance and duration of exposure. Responses include edema, acute to chronic inflammation, fibrosis, mucosal ulceration, degeneration, and necrosis. Attempts at repair include regeneration, hyperplasia, squamous metaplasia, hyperkeratosis, and neoplasia. Awareness of normal histology and zones of transition from squamous to respiratory epithelium in different areas of the larynx in different species is critical to avoid confusing normal epithelium with metaplasia or hyperplasia. Microscopic examination of laryngeal mucosa from animals exposed via inhalation and necropsied following a recovery period provides the opportunity to determine the degree of regression or progression of exposure-induced laryngeal lesions.     

Expression pattern of p63 in oral epithelial lesions and submucous fibrosis associated with betel-quid chewing in Sri Lanka

Betel-quid chewing, which is closely related to the high incidence of oral cancer, is prevalent in Sri Lanka. p63 has a remarkable structural similarity to p53, suggesting an aberrant expression in oral cancer. Using anti-p63 antibody and immunohistochemistry, the present study investigated the expression pattern of p63 in oral epithelial lesions, including different types of squamous cell carcinoma (SCC), different grades of epithelial dysplasia, and submucosal fibrosis associated with betel-quid chewing. Nuclear immunoreactivity for p63 was detected in all the cases, including normal oral epithelium and epithelial lesions. In normal oral epithelium, nuclear positivity for p63 was observed in some of the basal cell layers and focally in the parabasal layer. Nuclear positivity increased in the epithelial lesions. The percentage of positive nuclei in the epithelial lesions was significantly higher than in normal epithelium (P < 0.01) and was also significantly higher in oral submucosal fibrosis than in epithelial dysplasia (P < 0.05). The results indicate that the overexpression of p63 in oral precancerous lesions and SCC in betel-quid chewers in Sri Lanka may be a useful marker for oral precancerous lesions.     

Multiple organ invasion by viruses: pathological characteristics in three fatal cases of the 2009 pandemic influenza A/H1N1

To further understand the pathological characteristics of multiple organ involvement of the 2009 pandemic influenza A/H1N1 infection, tissues of bronchial mucosa, lung, myocardium, gastrocnemius, and liver from 3 patients with fatal A/H1N1 infections were investigated by light microscopy and transmission electron microscopy. In all 3 patients, bronchial mucosa showed necrotizing bronchiolitis, epithelial necrosis and desquamation, and squamous metaplasia, while lung consolidation or fibrosis was identified. Myocardium and gastrocnemius exhibited focal necrosis and fibrosis, surrounded by muscle cells showing features of cell damage. In liver, there was widespread fatty degeneration and necrosis, most often around the central lobular vein and portal area. Viral particles were found in all samples, frequently located in endothelium, epithelium, and muscle cells. The observations demonstrate that in fatal cases of A/H1N1 infection, viruses not only infect the respiratory system, but also engage in multiple organ invasions, causing pathologic changes.     

Ciliated hepatic foregut cyst with extensive squamous metaplasia: report of a case

Ciliated hepatic foregut cysts (CHFC) are rare cystic lesions of the liver composed of a ciliated pseudostratified columnar epithelium with mucous cells, connective tissue, and smooth muscles bundles. We report the first case of CHFC with extensive squamous metaplasia without dysplasia or carcinoma. A unilocular, avascular, hypoechoic 60-mm liver lesion located in segment IV was detected by ultrasonography in a 31-year-old woman. The cyst was surgically removed and was lined mainly by a regular squamous epithelium without keratin formation. After extensive sampling, a ciliated pseudostratified columnar epithelium with some alcian blue-positive goblet cells was identified. The lesion was totally examined and there was no epithelial dysplasia or carcinoma. Squamous epithelium is very rare in hepatic foregut cysts and may degenerate into squamous carcinoma. Squamous epithelium is also described in biliary cysts. When squamous epithelium is identified in a liver cyst, an extensive sampling is recommended to identify possible foci of squamous carcinoma and to classify more precisely the histological type of the lesion. Because some cases of squamous carcinoma have been described in CHFC, surgical removal of the lesion may be more appropriate than close follow-up or sclerosing therapy.     

Chronic pancreatitis as a predisposing factor in the development of pancreatic cancer. Histological and histochemical studies

The frequency of hyperplasia, squamous metaplasia and dysplasia were examined in glandular tissue from 20 pancreatic specimens resected due to chronic inflammation. Hyperplasia of the epithelium of large pancreatic ducts with formation of papillomatous outgrowths was present in 6 cases. Epithelial hyperplasia of small ducts occurred in 10 cases. Dysplasia and squamous metaplasia of the epithelium of ducts, hypertrophy, hyperplasia and dysplasia of acinar cells were found in 7 cases. In 10 pancreatic specimens hypertrophy and hyperplasia of cells of the islets of Langerhans were noted. Increased histochemical reactions to dehydrogenases and proteinic thiol groups were present in epithelial cells which demonstrated hypertrophy, hyperplasia, metaplasia or dysplasia. Diminution of the PAS reaction to neutral glycoproteins and intensification of the reaction to acid glycoproteins were also noted in the ductal epithelium. The results obtained suggest that chronic inflammation of the pancreas should be clinically regarded as predisposing to the development of pancreatic cancer.     

Intraepithelial ischemia is a principal factor promoting cancerization of the covering epithelial tissues

Prominent angiogenesis, which is a hallmark of invasive cancer is preceded at the precancerous stage by marked ischemia. Our hypothesis proposes a structural mechanism responsible for altering blood flow in the covering epithelium and leading to marked reduction of vascularization in the foci of dysplasia.This mechanism varies from one type of epithelium to another. In squamous epithelium only basal cells are in direct contact with stromal vessels. To supply nutrients to the rest of the cells located at different levels, the subjacent stroma forms excrescences which penetrate upward together with blood capillaries.As soon as precancerous dysplastic alterations start and progress the number of intraepithelial blood vessels simultaneously decreases, thus leading to ischemia which precedes or promotes malignization of the covering squamous epithelium.To compensate for the deficit in blood supply, the dysplastic cells penetrate deeper into the underlying stroma, commencing invasion. Thus, the cells destroy the subjacent stroma not because they are initially “malignant”, but due to ischemia which provokes the search for nutrients.Comparing squamous epithelium with glandular respiratory epithelium shows that the latter contains no blood capillaries at all. However, unlike squamous epithelial coverings, in respiratory epithelial covering, each cell is attached directly to the basal membrane and has ample access to the blood supply.Covering respiratory epithelium itself seldom gives rise directly to malignant growth. Cancerization of this type of epithelium occurs in the foci of squamous metaplasia. The latter are not supplied by a sufficient amount of blood vessels and in the majority of cases remain fragile and vulnerable structures, easily prone to malignization. Further study of these phenomenon should include the clarification of the influence of carcinogenic agents on the mechanism of adequate vascularization at the precancerous stage.     

Histological types and significance of bronchial epithelial dysplasia.

Pulmonary epithelium is known to undergo a preneoplastic process prior to the development of lung carcinoma. Squamous dysplasia and atypical adenomatous hyperplasia have been identified and classified as preinvasive lesions of squamous cell carcinoma and peripheral pulmonary adenocarcinoma, respectively. However, these commonly recognized preinvasive lesions do not completely explain the development of all histological types of lung carcinoma. By examining 114 resection lung specimens, we concluded that there are four histological patterns of bronchial epithelial dysplasia based on morphological features (basal cell dysplasia, columnar cell dysplasia, bronchial epithelial dysplasia with transitional differentiation, and squamous dysplasia). The histological patterns were further characterized by immunohistochemistry. Basal cell dysplasia was focally positive for cytokeratin (CK) 17 and 10/13; columnar cell dysplasia was generally positive for CK7, 8, and 18; bronchial epithelial dysplasia with transitional differentiation had a heterogeneous immunoprofile, while squamous dysplasia was positive for CK10/13 and focally positive for CK17. Various degrees of abnormal expression of p53 and Ki-67 were found in the different types of bronchial epithelial dysplasia. The cases were divided into three groups based on degree and extent of bronchial epithelial dysplasia. By Crosstabs McNemar test, the Mann-Whitney U-test (for two independent groups), the Kruskal-Wallis one-way nonparametric ANOVA (for >2 independent groups) and Spearman correlation analysis, the degree and extent of bronchial epithelial dysplasia was shown to be positively correlated with the incidence of bronchogenic carcinoma and multifocal primary lung carcinoma (P<0.05). These findings indicated the following: (1) bronchial epithelium can develop various patterns of dysplasia with abnormal/ambiguous cell differentiation and abnormal expressions of p53 and Ki-67. Thus, these bronchial epithelial dysplastic lesions may represent a preneoplastic process. (2) The degree of bronchial epithelial dysplasia may significantly predispose individuals to bronchogenic carcinoma and multifocal primary lung carcinoma.     

Alleviation of carrageenan-induced hepatotoxicity and acronecrosis by aprotinin.

Carrageenan was found to be hepatotoxic in mice. Raised serum transaminase activity after i.p. injection of carrageenan was correlated with histopathological changes in the liver. These included necrosis of individual hepatocytes and focal areas of necrosis, with associated fibrin thrombi, 12 h after carrageenan injection. Increased mitotic activity was observed at 72 h and extramedullary haemopoiesis was noted at Day 5. Acronecrosis, a further manifestation of intravascular coagulation, was evident within 24 h of carrageenan injection, becoming clearly demarcated by Day 5. Treatment with the anti-protease aprotinin alleviated both the hepatotoxicity and the incidence and extent of acronecrosis induced by carrageenan. The possible mechanism underlying the in vivo toxicity of carrageenan and its alleviation by aprotinin is discussed in the light of these and other findings.     

Sinusoidal circulatory disturbance by microthrombosis as a cause of endotoxin-induced hepatic injury

The present study was undertaken in rats to examine the significance of sinusoidal circulatory disturbance by microthrombosis in the pathogenesis of hepatic damage and dysfunction due to endotoxin. Administration of endotoxin induced fibrin deposits and infiltration of polymorphonuclear leukocytes in the sinusoids, focal random coagulative hepatocellular necrosis and elevation of serum transaminase activities. When heparin was given simultaneously with endotoxin, the formation of fibrin thrombus in the sinusoids was prevented, and the endotoxin-induced morphological and functional changes in the liver were markedly inhibited. Infusion of thrombin into the portal vein induced a large amount of fibrin thrombi in the sinusoids, focal random necrotic foci resembling the lesions produced by endotoxin and elevation of levels of serum transaminases. These experimental data suggest that disturbance of hepatic microcirculation by sinusoidal thrombosis is the necessary and sufficient condition for the development of endotoxin-induced hepatic injury.     

Bleomycin-induced injury and metaplasia of alveolar type 2 cells. Relationship of cellular responses to drug presence in the lung.

Metaplastic epithelial cells are often observed lining alveoli in bleomycin-induced pulmonary fibrosis. The hypothesis that these cellular changes are induced by the direct action of the drug on differentiating Type 2 cells is now examined in a sequential study to correlate the presence of 3H bleomycin in the lung with the pattern of injury and repair of the alveolar epithelium. A single intravenous dose or multiple small intraperitoneal doses induce focal necrosis of Type 1 epithelial cells followed by Type 2 cell regeneration. At the time of maximal deoxyribonucleic acid (DNA) synthesis in these cells, significant amounts of 3H bleomycin are demonstrable in the lung by scintillation counting; and in autoradiographs, the drug appears to concentrate in epithelial cells. Subsequently many abnormal Type 2 cells are seen. Some are binucleate, and others show nuclear disruption. The usual process of differentiation to Type 1 cells does not occur; instead, a variety of epithelial forms are found, including fetal-like tubular structures and ciliated and squamous metaplastic cells. The correlation of epithelial injury and repair with the direct demonstration of bleomycin in the lung indicates that Type 2 cells are susceptible to injury in the division and differentiation phases of the cell cycle and may then produce a variety of inappropriate alveolar lining cells.     

Immunohistochemical study on the liver in autopsy cases with disseminated intravascular coagulation (DIC) with reference to clinicopathological analysis

Summary Immunohistochemical and clinicopathological studies were performed in 27 autopsy cases with indisputable DIC, which had been selected from 1,800 autopsy cases of elderly people based on the following two criteria; 1. presence of fibrin thrombi in glomeruli, and 2. presence of fresh patchy necrotic foci in myocardium and/or fibrin thrombi in splenic sinuses. A high incidence of liver lesions (22/27) was revealed in autopsy cases with indisputable DIC. The liver lesions could be classified into four groups. Group-I (Central degeneration) was characterized by massive precipitation of fibrin irregularly around the central vein, causing parenchymal damage. Group-II (Central necrosis), showed coagulation necrosis in the cental zone due to circulatory disturbance caused by either shock as a cause of DIC or abrupt cessation of blood flow into the lobules following fibrin thrombus formation in vessels of Glisson's sheath. Both group-I and -II showed a short clinical duration of DIC. Group-III (Sinusoidal thrombosis), showed the presence of fibrin thrombi in sinusoids with mild parenchymal damage and long clinical duration of DIC. Group-IV (No thrombosis), showed neither parenchymal damage nor fibrin thrombi in sinusoids, but a long clinical duration of DIC.     

Thymidine phosphorylase expression in progression of cervical cancer: correlation with microvessel count, proliferating cell nuclear antigen, and apoptosis

AIMS: To determine how epithelial and stromal thymidine phosphorylase expression affects angiogenesis, rapid tumour growth, and decreased apoptotic activity in cervical cancer at varying stages of progression. METHODS: Epithelial and stromal thymidine phosphorylase expression, the microvessel count (reflected by factor VIII related antigen), and proliferating cell nuclear antigen (PCNA) were assessed immunohistochemically in 25 specimens of normal cervical epithelium, 35 of carcinoma in situ (CIS), 34 of microinvasive carcinoma, and 34 of invasive cervical squamous cell carcinoma. Apoptosis was evaluated by the terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labelling (TUNEL) method. The relation of epithelial and stromal thymidine phosphorylase expression to microvessel count, PCNA index, and apoptotic index was examined. RESULTS: Epithelial and stromal thymidine phosphorylase expression progressively increased along a continuum from normal epithelium to invasive squamous cell carcinoma. Epithelial and stromal thymidine phosphorylase expression showed a significant positive correlation with microvessel counts. Within each histological stage, CIS cases with high stromal thymidine phosphorylase expression, invasive squamous cell carcinoma cases with high epithelial thymidine phosphorylase expression, and microinvasive carcinoma cases with high thymidine phosphorylase expression in both epithelium and stroma had a significantly higher microvessel count. High epithelial thymidine phosphorylase expression was associated with a significantly higher PCNA index in CIS and microinvasive carcinoma, but not in invasive squamous cell carcinoma. No significant correlation was seen between apoptotic index and either epithelial or stromal thymidine phosphorylase expression or microvessel count. CONCLUSIONS: Epithelial and stromal thymidine phosphorylase expression may combine to promote angiogenesis during progression of cervical cancer, and epithelial thymidine phosphorylase expression may stimulate tumour cell proliferation in the early stages.     

Is there a Carcinoma in Situ of Gastric Mucosa?

Carcinoma in situ, a precancerous lesion in the strict sense, was first recognized in stratified squamous epithelia. It is characterized by markedly atypical cells replacing the autochthonous epithelial cells without stromal invasion, the basement membrane being well preserved. Notwithstanding gradual transitions between carcinoma in situ on the one hand and dysplasias and invasive cancer on the other hand, its histological separation from the latter is feasible in the uterine portio. Its recognition has decisive therapeutic and prognostic implications, particularly in view of the frequently observed latent period between purely superficial spread and early invasive growth. In contrast difficulties are encountered in applying the concept of Carcinoma in situ to mucosal lesions of the stomach, though an analogous replacement stage has to be postulated, because the gastric and cervical mucous membranes differ fundamentally in their structural characteristics. The epithelial cells of the surface, pits and tubular glands do exhibit progressive atypia during cancerization. However, the single-layered epithelium offers far less distinctive criteria than the stratified squamous epithelium. Newly formed glandular complexes cannot be accepted as evidence for in situ growth. The latent period between purely superficial replacement by atypical cells and invasion appears to be considerably shorter in the stomach than in the portio, probably because the mechanical resistance of the loosely textured gastric lamina propria is small. In addition, stromal invasion may originate from any one epithelial cell in the gastric mucosa, whilst it is just the basal layer from which invasively growing cells may emanate in the uterine portio. The occurrence of dysplasia in the mucosa of the stomach does not justify a gastrectomy, according to our current experience, there being no intervention in gastric surgery equivalent to that of conization.     

Arteriosclerosis Due to Homocyst(e)inemia: Failure to Reproduce the Model in Weanling Rabbits

Weanling rabbits were injected subcutaneously daily for 35 days with homocysteine thiolactone in an attempt to repeat the results of McCully and Ragsdale. We failed to produce sustained homocyst(e)inemia (or homocysteine thiolactonemia); indeed, transient homocyst(e)inemia could only be demonstrated with a much higher dose of the free base of homocysteine given intraperitoneally. Homocysteine thiolactonemia was observed up to 15 minutes, only after an intravenous injection of homocysteine thiolactone. Analysis of urine and various organs for free amino acids also failed to detect homocyst(e)ine or the thiolactone. Morphologically, we were unable to distinguish between the experimental and control animals.     

Plasma cells and immunoglobulin-synthesis in oral precancer and cancer

Summary The subepithelial and peritumoral inflammatory infiltrates of 202 oral premalignant and malignant lesions — 108 leukoplakias and 94 squamous cell carcinomata with different grades of dysplasia were examined using an immunoenzymatic method. In addition, the influence of radiation and bleomycin-therapy on the stromal reaction of 24 carcinomata was studied.The incidence of immunoglobulin labelled plasma cells (IgA and IgG) was twice as high in those cases of leukoplakia where dysplasia was present.The number of plasma cells, especially IgA- and IgG-containing plasma cells, decreased significantly with progressive tumor dedifferentiation.The plasma cell response differed before and after radiation with a decrease in IgA- and IgG-containing plasma cells after therapy. In contrast, bleomycin-therapy did not produce distinct changes in the humoral and cellular stromal reaction. In the epithelium, IgA and IgG were localized throughout all epithelial layers in leukoplakias with dysplasia. This finding indicates a leakage of locally synthesized immunoglobulins through an altered oral mucosa.This investigation reveals alterations in the local immune homoeostasis of the oral mucosa in premalignant and malignant lesions which varies with the grade of dysplasia, tumor differentiation and therapy.This study was supported by a grant from the Deutsche Forschungsgemeinschaft     

Vascular changes in radiation bowel disease

A series of 20 cases of radiation bowel disease (RBD) was studied qualitatively and the arterial changes were studied quantitatively. A control series of 45 cases was studied. In the control cases there were positive correlations between the medial thickness of all vessels studied and the diastolic blood pressure as well as the incidence of intimal fibrosis in both intramural and extramural arteries. The medial thickness in all the arteries in cases of RBD was significantly higher than in the controls. This was probably due to the large number of fibrin thrombi which increased the vascular resistance. The degree of intimal fibrosis of the intramural arteries and arterioles was significantly greater than in the controls. Similarly the incidence of intimal fibrosis in all arterioles and intramural arteries was greater than the control group. The degree of intimal fibrosis was related to the dose of radiation received. The effect of radiation was an on-going process since the percentage of arterioles with intimal fibrosis increased with the time after radiotherapy. Blood pressure and age played no part in these correlations in RBD. The most consistently observed qualitative changes in RBD were in the arteries, arterioles and to a lesser extent the veins. These showed fibrin thrombi, fibrinoid necrosis, subendothelial oedema and fibrin. Various stages of healing were seen in the vessels. We believe that the blood vessels are the main site of injury in RBD and that the endothelial cell is the initial target for radiation damage.     

Histopathological evaluation of disseminated intravascular coagulation in Haemophilus somnus infection in cattle

The frequency and distribution of fibrin thrombi (microthrombi) in the main organs of spontaneously infected cattle were investigated to evaluate disseminated intravascular coagulation (DIC) in Haemophilus somnus infection. This infection is well known as infectious thrombo-embolic meningo-encephalitis (ITEME) and is characterized histopathologically by formation of thrombi, necrosis of blood vessels and neutrophil infiltration. The precise pathogenic mechanism of this disease has not yet been fully elucidated. The liver, spleen, kidney, lung, heart and brain of 11 cattle showing thromboembolic meningo-encephalitis were examined histopathologically and special attention was paid to fibrin thrombi. PTAH staining showed a high frequency of fibrin thrombi in the small vessels and capillaries in more than 3 organs and all the cases were regarded as falling within the histopathological criterion of DIC. The results of the present study indicate that the pathogenesis of the infection is closely related to the DIC.     

Pathologic changes induced in respiratory tract mucosa by polycyclic hydrocarbons of differing carcinogenic activity.

Seven aromatic polycyclic hydrocarbons (PCHs) were investigated for their toxic effects on respiratory mucosa: benzo(e)pyrene (BeP), pyrene, anthracene, benz(a)anthracene(BaA), dibenz(a,c)anthracene(DBacA), benzo (a)pyrene (BaP), and dimethylbenz(a)anthracene (DMBA). The compounds were chosen because they comprise a spectrum of PCHs ranging from noncarcinogens, to initiators, to weak and strong carcinogens. All of them except DMBA are environmentally relevant chemicals. The chemicals were tested over an 8-week period. Heterotopic tracheal transplants were continously exposed and the histopathologic effects induced by the various PCHs were periodically assessed semiquantitatively. All PCHs exhibited varying degrees of toxicity for respiratory epithelium and submucosa. BeP clearly showed the least toxicity followed by pyrene and anthracene. BaA and DBacA caused marked epithelial and submucosal changes. In addition to epithelial hyperplasia, undifferentiated epithelium and squamous metaplasia developed. Marked mononuclear infiltration occurred in the subepithelial connective tissue. With BaP the epithelial and submucosal changes were similar but were much stronger. DMBA was the most toxic substance, causing epithelial necrosis followed by generalized keratinizing squamous metaplasia; the subepithelial changes consisted of an early acellular exudate and, later (at 8 weeks), marked condensation and hyalinization of the lamina propria. The toxic response pattern of the tracheal mucosa to carcinogenic agents was characterized by the chronicity of epithelial and connective tissue damage, as opposed to the short-lived hyperplastic and inflammatory response elicited by the noncarcinogens and weak initiators.     

Salmonella 3, 10:r: toxicity in rabbit ileum and liver by light and electron microscopy

Salmonella 3, 10:r:- (a monophasic variety of otherwise diphasic serotypes such as S. weltevreden and S. simi) Cell_free filtrate, when introduded into rabbit ligated ileal loops causes fluid exsorption, as studied 18-hr after treatment. Light microscopic histology of treated ileum shows denudation of the columnar epithelium at several places, thereby allowing the passage of the toxic principle into circulation. An important target organ, liver shows extensive centrilobular necrosis, as observed by light microscopy. Transmission electron microscopy of ileum reveals opening of membrane junctions between the adjacent cells of epithelial lining of the treated ileum at places, and focal devitalization including formation of intra-cellular membranous inclusinos. Electron microscopy of liver shows extensive damage and swelling of cytoplasmic membranes. However, the areas of darkly staining lamellae of granulated endoplasmic reticulum are also seen in stacks as will as dispersed. These studies stress that Salmonella toxic substances can cause extensive damage to intestine and liver both.     

Histopathologic changes in parotid gland parenchyma after fine needle aspiration biopsy of a Warthin's tumour. A case report

Fine needle aspiration biopsy of a non-tender tumour in the right parotid gland was performed in a 63-year-old man. A cytological diagnosis of Warthin's tumour was made. Six weeks later, the tumor was removed by a formal parotidectomy. During dissection of the marginal mandibular branch of the facial nerve, significant fibrosis in the surrounding soft tissues was noted, requiring resection of the nerve. We also found a metaplastic (infarcted) Warthin's tumour with focal necrosis surrounded by metaplastic squamous epithelium. There was extensive fibrosis within the adjacent atrophic parotid parenchyma, striated muscle and around peripheral nerves. Small arteries at the periphery of the tumour were occluded by thrombi. The authors believe that the fibrosis of the tissue adjacent to the tumour was more likely due to the ischemia than to a direct puncture trauma caused by the fine needle aspiration.