František Fakan

Phyllodes Tumour of the Breast : Immunohistochemical Study of 37 Tumours Using MIB1 Antibody

In our study, the expression of Ki-67 antigen in phyllodes tumours of the breast was investigated in order to estimate its significance in assessing the grade of malignancy and in predicting the clinical behaviour of these tumours. Formalin-fixed and paraffin-embedded tissue specimens of 37 cases of phyllodes tumour of the breast (eight graded as malignant and 29 as benign according to histopathological criteria) and 20 breast fibroadenomas were stained by an immunoperoxidase technique, using the monoclonal antibody MIB1 directed against cell proliferation-associated Ki-67 antigen. A MIB1 index was calculated to express the percentage of MIB1 positive proliferating stromal cells. Our data indicate that there are statistically significant differences in MIB1 indices between histologically benign and malignant phyllodes tumours (alpha = 0.001), between benign phyllodes tumour and fibroadenoma (alpha = 0.01), and between malignant phyllodes tumour and fibroadenoma (alpha = 0.001). Our results also indicate a good correlation between the conventional grading of phyllodes tumours based on histological criteria and MIB1 indices. However, little predictive value of the MIB1 index in phyllodes tumours of the breast can be derived from our study.

Papillary carcinoma of thyroid with exuberant nodular fasciitis-like stroma.

We describe two cases of papillary carcinoma of the thyroid containing prominent nodular, fasciitis‐like stroma. In one of the cases infiltration into the adjacent parathyroid gland and metastases to two cervical lymph nodes occurred. In the lymph nodes and the parathyroid gland the carcinoma grew without any fasciitis‐like stroma. This unusual change in tumour stroma seems to be reactive in nature and confined only to the thyroid and adjacent soft tissues.

Demonstration of needle-shaped hepatic inclusions in porphyria cutanea tarda using the ferric ferricyanide reduction test

In 18 of 19 biopsy and 2 of 3 autopsy samples of hepatic tissue from cases of porphyria cutanea tarda needle-shaped cytoplasmic inclusions are capable of reducing ferric ions in the ferric ferricyanide reduction test. Thanks to the resulting Turnbulls Blue the inclusions are clearly visible, which facilitates their histological demonstration. In 20 biopsy and 20 autopsy samples of hepatic tissue from cases other than porphyria cutanea tarda the inclusions are not present. These needle-shaped inclusions are thus considered to be a specific histological feature. The ferric ferricyanide reduction test represents a simple method for their visualization, which can be used in routine diagnostic practice.

Carcinoma arising in ectopic hamartomatous thymoma. An ultrastructural study.

We present the ultrastructural features of a case of adenocarcinoma arising in ectopic hamartomatous thymoma in a 31 year old man, in the supraclavicular location. The tumor had a cribriform adenomatous component with a granular cell quality and mimicked a metastatic carcinoma. Ultrastructurally, the spindle cell component revealed clusters of tonofilaments and the tumor cells were attached by well developed desmosomes. The cytoplasm of adenocarcinoma cells contained peculiar cup-shaped bodies derived from the endoplasmic reticulum wrapped around the mitochondria.

Nodular transformation of splenic red pulp due to carcinomatous infiltration. A diagnostic pitfall.

Autopsy of three women dying of disseminated carcinoma of stomach, colon, and breast, respectively, revealed a grossly unremarkable spleen. Microscopic examination demonstrated a nodular transformation of the red pulp, simulating a follicular lymphoma. Immunostaining revealed dissociated carcinomatous cells between the nodules, and this was thought to be the cause of the nodular transformation.

Oncocytic cystadenoma of the parotid gland with tyrosine-rich crystals.

A case of benign oncocytic cystadenoma with abundant intraluminal tyrosine-rich crystals involving the parotid gland is described.

Experimental hepatic uroporphyria induced by the diphenyl-ether herbicide fomesafen in male DBA/2 mice.

Hepatic uroporphyria can be readily induced by a variety of treatments in mice of the C57BL strains, whereas DBA/2 mice are almost completely resistant. However, feeding of the protoporphyrinogen oxidase-inhibiting herbicide fomesafen (0.25% in the diet for 18 weeks) induced hepatic uroporphyria in male DBA/2N mice (liver porphyrin content up to 150 nmol/g, control animals 1 nmol/g), whereas fomesafen-treated male C57BL/6N mice displayed only a slight elevation of liver porphyrins (approximately 5 nmol/g). The profile of accumulated hepatic porphyrins in fomesafen-treated DBA/2N mice resembled the well-characterised uroporphyria induced by polyhalogenated aromatic hydrocarbons, while histological examination confirmed the presence of uroporphyria-specific cytoplasmic inclusions in the hepatocytes. Uroporphyrinogen decarboxylase activity decreased to about 30% of control values in fomesafen-treated DBA/2N mice; microsomal methoxyresorufin O-dealkylase activity was slightly reduced. The amount of CYP1A1 and CYP1A2 mRNA, as determined by real-time PCR, was not significantly changed; mRNA encoding the housekeeping 5-aminolevulinic acid synthase was elevated 10-fold. Total liver iron was slightly increased. A similar uroporphyria was induced by the herbicide formulation Blazer, containing a structurally related herbicide acifluorfen, when fed to DBA/2N mice at a dose corresponding to 0.25% of acifluorfen in the diet. Since DBA/2 mice are almost completely resistant to all well-characterised porphyrogenic chemicals, the results suggest the possible existence of a yet unknown mechanism of uroporphyria induction, to which the DBA/2 mouse strain is more sensitive than the C57BL strain.

Liver preneoplastic changes in mice treated with the herbicide fomesafen

1 Effect of the diphenyl ether herbicide fomesafen on liver preneoplastic changes and porphyrin biosynthesis was examined in male C57BL/6J mice (0.23% in the diet for 14 months) and ICR mice (0.3% in the diet for 50 weeks). Fomesafen treatment resulted in preneoplastic changes (liver nodules and foci of altered hepatocytes) in both strains, uroporphyria developed only in ICR mice. 2 Iron pretreatment (600 mg/kg as a single dose) accelerated the development of fomesafen-induced preneoplastic changes in both mouse strains. The number of foci containing altered hepatocytes, as well as the number and size of liver nodules, were increased in iron-pretreated animals. 3 A single injection of iron induced marked uroporphyria in C57BL/6J mice after 14 months (liver porphyrin content 102 nmol/g). This uroporphyria was further potentiated by fomesafen administration (208 nmol/g). 4 In ICR mice, liver histology was apparently normal after a 3 month recovery from fomesafen treatment (0.32% for 9 months). Liver porphyrin content (260 nmol/g) started to decrease immediately after fomesafen withdrawal, but was still significantly elevated after 3 months (5 nmol/g), as compared to controls (1 nmol/g). 5 It is concluded that the toxicological evaluation of fomesafen should focus on liver porphyrin biosynthesis.

Liver cell cytoplasmic inclusions in experimental porphyrias: their demonstration with the ferric ferricyanide reduction reaction

In the present paper we describe needle-shaped and granular cytoplasmic inclusions in the liver cells of mice and rats with experimental porphyria biochemically resembling human porphyria cutanea tarda. The inclusions were inconspicuous in routine histological slides. The ferric ferricyanide reduction reaction, however, enabled us to demonstrate their shape and location within the hepatic lobule. Needle-shaped inclusions are considered to represent a structure specifically seen in experimental porphyrias resembling porphyria cutanea tarda. These structures are similar to the inclusions seen in human porphyria cutanea tarda.

Diagnostic value of PB/KOH/PAS method for identification of primary cancer from metastases

The demonstration of 0-acylated sialic acids in the mucin of cancer metastases by Cullings periodic acid-borohydride-potassium hydroxide-periodic acid-Schiff method (PB/KOH/PAS) is helpful in distinguishing between mucin-producing primary colorectal adenocarcinoma (which will be in 60 to 70% positive) and mucin-producing primary lung adenocarcinoma (which will be negative). In addition to colorectal mucin, the 0-acylated sialic acids may be demonstrated in the mucin of some gastric and gallbladder carcinomas, and only exceptionally in pancreatic, ovarian, and prostatic cancers.