bluuebunny/crossref_metadata_2025 huggingface dataset:
Cellular proliferation and nuclear ploidy assessments augment established prognostic factors in predicting malignancy in testicular Leydig cell tumours
Authors: McCluggage W G , Shanks J H , Arthur K , Banerjee S S
Published: March 2003

Aims

Testicular Leydig cell tumours are rare. Although most behave benignly ≈ 10% are malignant. Clinicopathological features have been described which have some value in predicting malignant behaviour, although as with other endocrine tumours uncertainties remain in many individual cases. Our aim was to determine the clinicopathological features of 20 testicular Leydig cell tumours. We wished to investigate whether, in addition to established clinicopathological features, the MIB1 index and/or flow cytometric analysis of nuclear DNA content are of value in predicting malignancy. We also wished to investigate the frequency of p53 protein accumulation in these neoplasms.

Methods and results

Twenty testicular Leydig cell tumours were studied and the clinical case notes examined. Histological sections were assessed by pathologists involved in the study. Pathological features evaluated included: tumour size, extratesticular extension, nuclear pleomorphism, mitotic activity, necrosis and vascular invasion. Immunohistochemical staining was performed with the anti‐p53 monoclonal antibody DO‐7 and the cell proliferation marker MIB1. A flow cytometric analysis of nuclear DNA content was also performed. Three tumours behaved in a malignant fashion with the development of metastases. Another had morphological features of malignancy but the patient died a short time after diagnosis from unrelated causes. These four neoplasms were larger than benign tumours, often contained areas of necrosis and sometimes exhibited vascular invasion. They generally exhibited greater nuclear pleomorphism and a higher mitotic rate than benign tumours. Three of the four malignant tumours had a high MIB1 index (20–50%) and the fourth exhibited DNA aneuploidy by flow cytometry. Two malignant tumours showed increased expression of p53 protein, with ≈ 50% of nuclei staining with DO‐7. All benign tumours had a low MIB1 index (0–2%) and a diploid DNA profile, except for one case where there was DNA aneuploidy. There was little or no staining of benign tumours with DO‐7.

Conclusions

The study confirms that large size, marked nuclear pleomorphism, high mitotic rate, necrosis and vascular invasion are important factors in predicting malignant behaviour in testicular Leydig cell tumours. Additional prognostic value may be derived from the MIB1 index and flow cytometry. Accumulation of p53 protein, through mutational or other events, may be important in malignant progression in these tumours.
c‐erbB‐2 protein is expressed in hepatolithiasis and cholangiocarcinoma
Authors: Terada T , Ashida K , Endo K , Horie S , Maeta H , Matsunaga Y , Takashima K , Ohta T , Kitamura Y
Published: March 2003

Aims

The c‐erbB‐2 proto‐oncogene encodes a transmembrane protein which is highly homologous to epidermal growth factor receptor. Overexpression of this c‐erbB‐2 protein has been reported in many human carcinomas, including breast carcinoma. However, there have been few studies of the expression of c‐erbB‐2 in cholangiocarcinoma and hepatolithiasis, a condition occasionally associated with cholangiocarcinoma.

Methods and results

In this study, we evaluated immunoreactivity for the c‐erbB‐2 protein in human cholangiocarcinomas (n = 47), hepatolithiasis (n = 20), fetal livers (n = 36) and normal adult livers (n = 6). In normal adult livers and fetal livers, expression of c‐erbB‐2 protein could not be detected in hepatocytes or intrahepatic biliary cells. In hepatolithiasis, there was overexpression of c‐erbB‐2 in 15/20 (75%). The expression was found with a membranous pattern on the proliferated intrahepatic bile ducts and proliferated intrahepatic peribiliary glands around the bile ducts containing stones. Hepatocytes were negative for c‐erbB‐2 protein. Moreover, the biliary cell expression of the c‐erbB‐2 protein correlated significantly with Ki67 labelling index. On the other hand, aberrant expression of c‐erbB‐2 was found in 33/47 (70%) cholangiocarcinomas. The c‐erbB‐2 expression in cholangiocarcinomas did not correlate with Ki67 labelling index or p53 expression.

Conclusions

These results indicate that aberrant expression of c‐erbB‐2 protein is found in cholangiocarcinoma and also in noncancerous biliary proliferative lesions such as hepatolithiasis. These findings also suggest that c‐erbB‐2 oncogene participates not only in cholangiocarcinogenesis but also in biliary cell proliferation in non‐neoplastic conditions.
Mucoepidermoid carcinoma arising in Warthin's tumour of the parotid gland: report of two cases with histopathological, ultrastructural and immunohistochemical studies
Authors: Nagao T , Sugano I , Ishida Y , Tajima Y , Furuya N , Kondo Y , Nagao K
Published: March 2003

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.
Crystal‐storing histiocytosis and immunocytoma associated with multifocal fibrosclerosis
Authors: García J F , Sánchez E , Lloret E , Martín J , Piris M A
Published: March 2003

Aims

Crystal‐storing histiocytosis is a rare disorder described in patients with lymphoproliferative diseases, mainly in cases of multiple myeloma but also in lymphoplasmacytic lymphoma (immunocytoma). Most cases involve one single organ which, in the majority, is related directly to the presence of tumour. We describe a 44‐year‐old man with a clinical picture of multifocal fibrosclerosis (with mesenteric panniculitis, peritoneal, mediastinal and orbital fibrosis) in which the autopsy showed a systemic infiltrate of crystal‐storing histiocytes and functional alteration of the organs involved, associated with IgG‐kappa type immunocytoma.

Methods and results

Histology showed a systemic infiltration, with a predilection for adipose tissue, by a diffuse cellular infiltrate composed of small lymphocytes, plasmacytoid lymphocytes and plasma cells, admixed with large number of crystal‐storing histiocytes. Intracytoplasmic crystals were not identified either in the plasma cells or plasmacytoid lymphocytes. The neoplastic cells and the crystalline inclusions displayed reactivity with antibodies for IgG and the kappa light chain. A polymerase chain reaction study for the IgH gene showed a monoclonal rearrangement. Ultrastructural studies showed needle‐shaped crystals surrounded by a single unit membrane.

Conclusion

This case is, to the authors' knowledge, the first to be described in which crystal‐storing histiocytosis is associated with a clinical picture of multifocal fibrosclerosis, which suggests that lymphoproliferative processes should be considered in the differential diagnosis of the various conditions associated with multifocal fibrosclerosis.
Perforin and Fas pathways of cytotoxic T‐cells in histiocytic necrotizing lymphadenitis
Authors: Ohshima K , Shimazaki K , Kume T , Suzumiya J , Kanda M , Kikuchi M
Published: March 2003

Aims

Cell death can be divided into necrosis and apoptosis. In histiocytic necrotizing lymphadenitis (HNL), apoptosis is the main form of cell death. Two molecular mechanisms of T‐cell‐mediated cytotoxicity, one perforin‐based and the other Fas‐based, have been demonstrated, and both systems induce apoptosis of the target cells. This study was designed to investigate the Fas and perforin pathways in HNL.

Methods and results

Twelve cases of HNL were analysed using immunohistochemical staining. The Fas and/or FasL‐positive cells, including lymphocytes and histiocytes, were frequently encountered in the necrotizing lesions, however, they were rare in the nonpathological regions. The perforin and/or granzyme‐positive cells were also confined in the necrotizing lesions. In double staining, CD8‐positive lymphocytes occasionally expressed Fas and/or FasL, and histiocytes also expressed FasL and/or Fas. However, CD4‐positive lymphocytes rarely expressed FasL and/or Fas. In a flow cytometric analysis, most of the cytotoxic T‐cells, which were recognized by cytolytic granules of TIA‐1 and considered to be CD8‐positive lymphocytes, expressed FasL and Fas. The perforin‐positive lymphocytes also expressed FasL and Fas.

Conclusion

In our previous study, the apoptotic cells were T‐cells, especially CD8‐positive cells rather than CD4‐positive cells. Based on these findings, in Fas and perforin pathways, the CD8‐positive cells were considered to be effector and target cells, while histiocytes could possibly be enhancers. As a result, both pathways seemed to induce an abundance of apoptosis and thus induce necrotizing lesions.
Prognostic comparison of the pathological classifications of gastric cancer: a population‐based study
Authors: Roy P , Piard F , Dusserre‐Guion L , Martin L , Michiels‐Marzais D , Faivre J
Published: March 2003

Aims

There is controversy over the value of the pathological classifications of gastric carcinomas in the prediction of patient survival. This study was designed to assess the prognostic value of four widely used pathological classifications, in addition to classical prognostic factors.

Methods and results

Records from the population‐based registry of digestive tract tumours in the department of Côte d'Or (France) have been analysed. All available histopathological slides of gastric cancer resected between 1976 and 1985 were reviewed and classified according to World Health Organization (WHO), Laurén, Ming and Goseki pathological coding systems. A relative survival analysis was performed using a relative survival model with proportional hazard applied to net mortality by interval. WHO, Laurén or Goseki classifications were not found to be independent prognostic factors. In addition to advanced age group, depth of parietal involvement, nodal involvement, presence of metastases, tumour site and gross appearance of the tumour, the Ming's infiltrative type was associated with a lower survival.

Conclusion

This study suggests an independent prognostic value of the Ming subtypes with respect to survival in patients resected for gastric carcinoma.
Liposarcoma with meningothelial‐like whorls: a study of 17 cases of a distinctive histological pattern associated with dedifferentiated liposarcoma
Authors: Fanburg‐Smith J C , Miettinen M
Published: March 2003

Aims

We reviewed 17 cases of liposarcoma with peculiar meningothelial‐like whorls to determine the pathological and clinical significance of this distinctive morphological finding.

Methods and results

Seventeen liposarcomas with concentric whorls simulating the whorls seen in meningioma, were retrieved from the soft tissue registry of the Armed Forces Institute of Pathology. There were 10 males and seven females with a mean age of 53 years (range 24–76 years). Twelve of the 17 cases were large retroperitoneal tumours (mean 170 mm in greatest dimensions). All 17 cases had whorls. Three cases were classified as well‐differentiated liposarcoma with whorls and bone formation. Five cases showed coalescing of whorls into areas which may be interpreted as low to intermediate grade dedifferentiation. Five cases had spindled areas associated with the whorls which correlate with classical intermediate to high‐grade dedifferentiation, Finally, four cases had a predominant spindle cell component resembling malignant fibrous histiocytoma with focal residual possible sclerosing well‐differentiated liposarcoma (scattered adipocytes, adipocytic atypia and/or floret‐type giant cells). The meningothelial‐like whorls were clustered or scattered throughout the tumours and ranged from 0.09 mm to over 10 mm in diameter in cases with coalescent whorls. Metaplastic bone was present within the whorls or in their immediate vicinity in 10 of 17 cases. Immunohistochemically, the whorl‐forming spindle cells showed α‐smooth muscle actin reactivity in three of seven cases but were negative for epithelial membrane antigen, CD21, and CD35 indicating lack of relationship with meningioma and dendritic reticulum cell sarcoma, other tumours that may contain whorls. Whorls with bone formation revealed cells adjacent to the bone to be positive for osteocalcin, a marker of osteoblastic phenotype. The spindle cells of the whorls were negative for CD34 and CD31, yet these highlighted numerous capillaries inside the whorls in a concentric manner. The whorl‐forming cells showed moderate to high MIB‐1‐index and showed p53 immunoreactivity similar to the dedifferentiated areas but differed from the areas of well‐differentiated liposarcoma, which were p53‐negative and showed a low MIB‐1‐index. Follow‐up (available in 65% cases) revealed seven patients with metastases or dead of the disease and five patients with one or more recurrences.

Conclusions

The meningothelial‐like whorls represent a mesenchymal proliferation which may undergo pericytic or myofibroblastic, or occasionally osteoblastic, differentiation in liposarcoma. These whorls do not represent dendritic or perineurial/meningothelial differentiation. The significant proliferative activity, p53 reactivity and tendency to coalesce and associate with dedifferentiated liposarcoma suggest that the meningothelial whorls may represent an early sign of dedifferentiation of liposarcoma.
Malignant proliferating trichilemmal tumours: an histopathological and immunohistochemical study of three cases with DNA ploidy and morphometric evaluation
Authors: Herrero  , Monteagudo  , Ruiz  , Llombart‐Bosch
Published: March 2003

Aims: Malignant proliferating trichilemmal tumours (MPTT) are rare neoplasms capable of tissue invasion and metastasis, the diagnosis of which is based essentially on histological features. In difficult cases, however, evaluation of additional parameters may be needed to diagnose malignancy.

Methods and results

We report three cases of MPTT in which, in addition to the histological features, we have determined the DNA ploidy, nuclear area and proliferative fraction. CD34 immunoreactivity has also been tested. Two cases were aneuploid, and one diploid with increased proliferating index. PCNA immunostaining labelled 40% and 80% of tumour cells in aneuploid tumours and 30% of the diploid neoplasm. In all cases, nuclear area was consistent with large pleomorphic tumour cells. No CD34 immunostaining was detected.

Conclusions

Aneuploidy is common in MPTT, particularly in tumours with a high proliferative fraction. Loss of CD34 immunoreactivity is an additional feature of potential, though limited, value. Therefore, evaluation of the DNA content, proliferation markers and CD34 immunostaining may be helpful in the diagnosis of MPTT.
Recent advances in the histopathology and molecular pathology of carcinoma of the endometrium
Authors: Burton J L , Wells M
Published: March 2003

Endometrial carcinoma is the commonest malignancy of the female genital tract. The pathogenesis is complex and at least three pathogenetic subtypes exist with different prognostic implications. The molecular events involved remain poorly defined but several genes are involved and mutations of tp53, WAF1/CIP1, PTEN, bcl‐2 and c‐erbB‐2 have been implicated. Although care is needed in interpreting the results, the majority of these mutations can be detected immunohistochemically and therefore have the potential to aid the pathologist and surgeon in assessing the prognosis of a tumour. However, for the time being, no molecular marker is as valuable in determining prognosis as conventional parameters such as tumour type, grade and vascular space involvement.
Sustentacular cells in pulmonary neuroendocrine tumours
Authors: Gosney  , Denley  , Rešl
Published: March 2003

Aims

To determine the prevalence of sustentacular cells across the range of pulmonary neuroendocrine tumours: typical and atypical carcinoid tumours and large cell and small cell neuroendocrine carcinomas.

Methods and results

Sustentacular cells were sought in 80 pulmonary neuroendocrine tumours by immunolabelling for S100 protein, nerve growth factor receptor and glial fibrillary acidic protein. Intratumoural macrophages and Langerhans cells were identified with the KP 1 (CD68) and CD1A antibodies. S100‐positive sustentacular cells were present in 25 of 30 typical carcinoids, 20 of 25 atypical tumours, six of 10 large cell carcinomas and six of 15 small cell lesions. They were most numerous in the typical carcinoids but very few in the small cell carcinomas, their prevalance being clearly related to grade of differentiation and, in particular, to the degree of architectural organization.

Conclusions

Sustentacular cells are often found in pulmonary neuroendocrine tumours, especially better‐differentiated lesions with a well‐developed architecture, their prevalence clearly reflecting the degree of structural organization. Whether their prevalence is a useful prognostic indicator within a particular group of such tumours, such as the atypical carcinoids or the large cell carcinomas, as appears to be the case with paragangliomas, is unclear.
Haemophilic arthropathy resembles degenerative rather than inflammatory joint disease
Authors: Roosendaal  , van Rinsum  , Vianen  , van den Berg  , Lafeber  , Bijlsma
Published: March 2003

Aims

To investigate the pathogenetic mechanisms of haemophilic arthropathy (HA) by comparing end‐stage arthropathy with osteoarthritis (OA; a degenerative joint disorder) and rheumatoid arthritis (RA; an inflammation‐mediated joint disease).

Methods and results

Cartilage and synovium from patients with HA (n = 10), RA (n = 8), OA (n = 14) and normal control subjects (n = 6) were examined morphologically, biochemically and histochemically. Cartilage in HA exhibited characteristics of degenerative joint disease (OA), as evidenced by morphological, histochemical (Safranin‐O fast green‐iron haematoxylin, Mankin grade) and biochemical (proteoglycan synthesis, glycosaminoglycan content and DNA content) changes, whereas synovium in HA showed characteristics of inflammation‐mediated joint disease (RA), as evidenced by histochemical (inflammation, haematoxylin and eosin (H&E) and iron deposition, Perls' blue) and biochemical changes (interleukin (IL)‐1, IL‐6, tumour necrosis factor (TNF)α and catabolic properties).

Conclusion

Haemophilic arthropathy shows characteristics of both inflammatory and degenerative joint disease. On the basis of these results and published information, it appears that degenerative cartilage changes have a dominant role in HA and are augmented by relatively mild inflammation of the synovium.
PCR‐based clonality analysis: a reliable method for the diagnosis and follow‐up monitoring of conservatively treated gastric B‐cell MALT lymphomas?
Authors: Aiello  , Giardini  , Tondini  , Balzarotti  , Diss  , Peng  , Delia  , Pilotti
Published: March 2003

Aims

We evaluated polymerase chain reaction (PCR) amplification of specific immunoglobulin heavy chain (IgH) gene rearrangements as a means of demonstrating monoclonality during follow‐up of conservatively treated gastric MALT lymphoma, and compared the reproducibility of PCR on sequential frozen and paraffin‐embedded endoscopic biopsies. We established an association between clonality detected by PCR and the histological observations.

Methods and results

Sixty‐nine pairs of sequential frozen and paraffin‐embedded endoscopic biopsies from 21 conservatively treated patients were graded according to the Wotherspoon–Isaacson histological scoring system, which provides a measure of diagnostic confidence on a scale 0–5. PCR amplification of the IgH gene was performed using FR3/JH and FR2/JH primers. 68/69 paired samples (98.5%) showed identical mono‐ or polyclonal PCR amplification patterns. Forty‐seven out of 48 pairs of samples sharing similar histological features produced identical amplification patterns in both fresh and paraffin‐embedded tissues. In comparison with the histological grading, monoclonality was detected in 64.2% and 41.6% of samples scored 5 and 4, respectively. Conversely, among 64 samples scored 0–3, a monoclonal pattern was observed only in two samples, one of which was from a patient who relapsed 9 months later.

Conclusions

PCR‐based clonality analysis by demonstration of specific IgH gene rearrangement can be easily and reliably performed on both frozen and paraffin‐embedded endoscopic biopsies. In conjunction with histological observation, this method can be used as a complementary tool to monitor MALT lymphoma regression during conservative treatment.
Nuclear expression of p53, p21 and cyclin D1 is increased in bronchioloalveolar carcinoma
Authors: McDonald  , Pilgram
Published: March 2003

Aims

The objectives of this study were: (1) to determine, using immunohistochemistry, the level of expression of the cell cycle factors p53, p21 and cyclin D1 in a group of bronchioloalveolar carcinomas (BACs), and to compare these data to relevant published data for lung carcinoma; (2) to determine if higher expression rates for these factors in BAC were associated statistically with advanced clinical stage, greater tumour size, tobacco abuse, and/or BAC subtype; (3) to seek, using Fisher's exact t‐test and paired data groups, any significant associations within the expression data for p53, p21 and cyclin D1.

Methods and results

A panel of monoclonal antibodies against p53, p21 and cyclin D1 was applied to 19 bronchioloalveolar carcinomas (17 surgical pathology cases and two autopsies) from the tissue archives of St. Louis University. These immunohistochemical stains were graded on a semiquantitative scale according to the prevalence of nuclear staining within the tumour (< 10% positive cells = 0, 10–25% = 1+, 25–50% = 2+, 50–75% = 3+ and 75–100% = 4+). Six of 19 (32%) of BACs showed 1+ or greater p53 positivity, six of 19 (32%) showed 1+ or greater nuclear cyclin D1 positivity, and nine of 19 (47%) of BACs showed 1+ or greater p21 nuclear positivity. A statistically significant correlation was found between p53 and cyclin D1 expression (P = 0.046, Fisher's exact t‐test), but not between p53 and p21, or between p21 and cyclin D1. No statistically significant association was found between the cell cycle factor expression data and subtype of BAC (mucinous vs. nonmucinous), tumour diameter, clinical stage or tobacco‐use history.

Conclusions

BACs show p53 immunostain positivity at a frequency similar to that published for p53 mutations in lung adenocarcinomas in general. Cyclin D1 and p21 nuclear expression characterizes a significant proportion of BACs, with cyclin D1 and p53 expression showing a statistically significant association. Aberrations in p53, p21, and cyclin D1 expression may be important in the development of a significant proportion of BACs.
The value of histomorphometric nuclear parameters in the diagnosis of well differentiated follicular carcinomas and follicular adenomas of the thyroid gland
Authors: Eldar  , Sabo  , Cohen  , Misselevich  , Abrahamson  , Cohen  , Kelner  , Boss
Published: March 2003

Aims

To explore the potential of histomorphometric analysis in distinction between follicular adenomas and well differentiated follicular carcinomas of the thyroid gland. Their differentiation on routine histological study may be a challenging exercise, being contingent upon the absence or presence of vascular invasion and penetration of neoplastic follicles through the capsule of the tumour.

Methods and results

Computer‐assisted image analysis was performed to gauge the nuclear area, nuclear Ferret diameter, nuclear regularity factor, nuclear elongation factor, number of nuclear vesicles and total area of all nuclear vesicles in the follicles of 37 adenomas and 36 well differentiated carcinomas. By univariate analysis, these nuclear descriptors (with the exception of the elongation factor) were found to correlate with the benign or malignant nature of the tumours. By multivariate analysis, only the nuclear area, Ferret diameter and regularity factor were ascertained to be significant predictors of malignancy. A fitted logit model correctly predicted 91% of the cancers and 87% of the adenomas.

Conclusions

Histomorphometrically gauged nuclear parameters of the tumour cells may reinforce pathologists' decision‐making by adding objective and unbiased criteria to their subjective assessment of follicular neoplasms in cases in which vascular or capsular invasion are not detected.
Reliability of intraoperative frozen section and imprint cytological investigation of sentinel lymph nodes in breast cancer
Authors: Van Diest P J , Torrenga H , Borgstein P J , Pijpers R , Bleichrodt R P , Rahusen F D , Meijer S
Published: March 2003

Aims

The sentinel lymph node procedure enables selective targeting of the first draining lymph node, where the initial metastases will form. A negative sentinel node (SN) predicts the absence of tumour metastases in the other regional lymph nodes with high accuracy. This means that in the case of a negative SN, regional lymph node dissection is no longer necessary. Besides saving costs, this will prevent many side‐effects of lymph node dissection. The aim of this study was to evaluate the reliability of intraoperative cytological and frozen section investigation of the SN to detect metastases. This would allow the axillary lymph node dissection to be performed in the same session as the SN procedure and the excision of the primary tumour in case of a positive SN.

Methods and results

Seventy‐four SNs were detected by gamma probe detection of nanocolloid and visual localization of Patent Blue accumulations in 54 women with stage T1–2N0M0 invasive breast cancer. The identified SN were immediately investigated by frozen section and imprint cytological investigation. Diagnoses were confirmed on the paraffin material, and in case of negative frozen section and paraffin haematoxylin and eosin sections, skip sections and immunohistochemistry were performed. Thirty‐one SNs (42%) contained metastases, of which 27 were detected by the frozen section procedure (sensitivity 87%). There were no false positives (specificity 100%). The sensitivity of the imprints was 62% with a specificity of 100%. When evaluating the data per patient, for the frozen section procedure the sensitivity was 91% and the specificity 100%, and for the imprints, the sensitivity was 63% and the specificity 100%. There were no SNs in which the imprints showed metastases and the frozen section did not.

Conclusions

Intraoperative frozen section analysis is a reliable procedure by which a high percentage of sentinel lymph node metastases can be detected in breast cancer patients without false positive results. This allows the surgeon to perform an immediate axillary lymph node dissection in case of positive SNs. In up to 10% of cases, the final paraffin sections will reveal micrometastases that were not detected by the frozen section, and in these patients axillary lymph node dissection will have to be performed in a second session. The imprint method is significantly less sensitive than the frozen section but may be used as an alternative when frozen section is not possible.
Scarring in papillary carcinoma of the thyroid: report of two new cases with exuberant nodular fasciitis‐like stroma
Authors: Toti  , Tanganelli  , Schürfeld  , Stumpo  , Barbagli  , Vatti  , Luzi
Published: March 2003

Aims

To describe two new cases of papillary carcinoma of the thyroid with exuberant nodular fasciitis‐like stroma, one of which was characterized by previously unreported transformation into a poorly differentiated lesion. Moreover, we explore the presence of TGF‐β to help to clarify the pathogenesis of the collagen formation.

Methods and results

The case characterized by an aggressive behaviour exhibited areas of transformation into a poorly differentiated (insular) carcinoma of the thyroid. In both cases, as revealed by immunohistochemistry, neoplastic cells produced and secreted high amounts of TGF‐β. On the contrary, TGF‐β immunoreaction was never present in the normal thyroid or in papillary carcinomas without collagen bundles, while a weak, exclusively intracellular reaction was present in a patchy manner in cases showing intratumoral fibrous bundles.

Conclusions

The rare variant of papillary thyroid carcinoma characterized by exuberant stroma may give rise to more aggressive lesions, as do other histotypes of differentiated thyroid carcinomas. TGF‐β, the fundamental cytokine which mediates scarring and activation of myofibroblasts, most probably induces the exuberant stroma.
Absence of Epstein–Barr virus (EBV) in intrahepatic cholangiocarcinoma confirmed by lack of EBV‐coded nuclear RNA and latent membrane protein‐1
Authors: Ozaki  , Harada  , Watanabe  , Furubo  , Tsui  , Nakanuma
Published: March 2003

Aims

Studies are disclosing that Epstein–Barr virus (EBV) is involved in the aetiology of various neoplasms including undifferentiated carcinomas of the aerodigestive tract. The aetiology of intrahepatic cholangiocarcinoma (ICC), a malignant neoplasm arising from intrahepatic biliary epithelia, has yet to be fully evaluated. To date, two cases of EBV‐related ICC have been reported, and they presented foci of lymphoepitheliomatous undifferentiated carcinoma components.

Methods and results

To determine whether EBV is commonly involved in the developments of ICC, we performed in‐situ hybridization and immunohistochemistry for EBV in 215 cases of ICC in Japan, using a probe against EBV‐coded nuclear RNA (EBER) and a specific antibody against latent membrane protein‐1 (LMP‐1), respectively. We did not detect EBV‐infected carcinoma cells in any of the ICC cases examined. No lymphoepitheliomatous undifferentiated carcinoma components were found either.

Conclusion

The results suggest that EBV infection is unlikely to be involved in the pathogenesis of ICC.
Reduced expression of the cell‐cycle inhibitor p27Kip1 is associated with progression and lymph node metastasis of gastric carcinoma
Authors: Kim  , Lee  , Nam  , Shin  , Sohn  , Park  , Yoon  , Song  , Park
Published: March 2003

Aims

p27Kip1 (p27), a cyclin‐dependent kinase inhibitor, plays an important role as inhibiting the progression of the cell cycle. Decreased expression of p27 is associated with high histological grade and aggressiveness of several human tumours. We aimed to evaluate the role of p27 in the progression and metastasis of gastric carcinoma.

Methods and results

We analysed the expression of p27 in 67 primary gastric carcinomas and 31 lymph node metastases by immunohistochemistry. Reduced expression of p27 was found more frequently in advanced gastric cancer (40.9%) than in early gastric cancer (15.6%) (P < 0.001). Decreased p27 expression correlated with large tumour size, high histological grade, lymphatic invasion, advanced stage, deep invasion, lymph node metastasis and recurrence. The expression of p27 showed an inverse correlation with the Ki67 labelling index. There was a significant reduction of p27 expression in metastatic tumour cells in lymph nodes (mean positive cells: 3.7%) when compared to the corresponding primary gastric carcinomas (mean positive cells: 8.1%) (P = 0.008).

Conclusions

Alterations of p27 expression may play an important role in the progression and metastasis to lymph node of tumour cells in human gastric carcinoma.
Smooth muscle metaplasia in ovarian endometriosis
Authors: Fukunaga
Published: March 2003

Aims

Little is known about smooth muscle metaplasia (SMM) in ovarian endometriosis. The clinicopathological significance of SMM in ovarian endometriosis is analysed.

Methods and results

Three hundred and twenty‐seven consecutive cases of ovarian endometriosis, including 58 cases associated with malignant ovarian epithelial tumour, between 1987 and 1996 were retrieved from hospital files and clinicopathologically analysed. The ages of the patients who showed SMM in ovarian endometriosis ranged from 28 to 70 years (average, 43.8 years). SMM was observed in 58 cases (17.7%); in 51 of 269 cases without tumour (19.0%) and in seven of 58 with tumour (12.1%). The differences in the incidence of SMM in cases with and without tumour were not statistically significant. SMM was a focal, microscopic change and there was neither smooth muscle tumour nor uterus‐like mass. Sixteen cases had short fascicles or stellate foci of SMM in the endometriotic stroma, an incomplete rim of SMM surrounding the endometriotic cysts was present in 32 cases, and 10 cases showed SMM in both the endometriotic stromal and incomplete rim of the endometriotic cysts. There was no significant histological difference in SMM between cases with and without malignant ovarian epithelial tumour.

Conclusions

SMM in ovarian endometriosis is not an uncommon phenomenon. SMM may be explained in two ways. First, smooth muscle originates from metaplastic endometrial stromal cells in endometriotic foci. Second, it originates from metaplastic ovarian stromal cells in the rim of endometriosis.
Hot spot microvessel density and the mitotic activity index are strong additional prognostic indicators in invasive breast cancer
Authors: De Jong  , Van Diest  , A Baak
Published: March 2003

Aims

Recent studies have drawn attention to intratumoral microvessel density (MVD) as a prognostic factor in invasive breast cancer. Various methods have been applied to assess MVD and the prognostic value of MVD in different studies varies considerably. Counting of microvessels in the most highly vascularized area (hot spot) of a tumour is the method most widely used. In this study we compared three counting methods.

Methods and results

To assess MVD in 112 cases of invasive breast cancer with long‐term follow‐up we performed microvessel counting in the hot spot of the tumour in four and 10 fields of vision (HS‐MVD4 and HS‐MVD10) and microvessel counting in 10 fields of vision distributed systematically over the whole tumour area (global MVD). The HS‐MVD4, HS‐MVD10 and global MVD showed good correlations with each other. HS‐MVD4 provided the highest number of microvessels (median value 71) followed by HS‐MVD10 and global MVD, with median values of 58 and 39, respectively. HS‐MVD4 showed the best prognostic value for overall survival (P = 0.0001) whereas HS‐MVD10 showed less (P = 0.01) and the global MVD showed no (P = 0.75) prognostic value. In univariate analysis, the HS‐MVD4 was the second strongest prognostic factor after tumour size. In multivariate survival analysis, the HS‐MVD4, mitotic activity index (MAI), lymph node status and tumour size were found to be independent prognostic factors. When combining MVD4 and MAI in lymph node negative patients, none of the patients with low MVD (< 71/mm2) and a low MAI (< 10 per 10 HPF) died, in contrast to patients with a high MVD or high MAI who have a 10‐year survival of 57%.

Conclusions

These data suggest that the hot spot MVD in four fields of vision is a major independent prognostic factor for overall survival in invasive breast cancer. For the first time, it is shown that hot spot MVD provides additional prognostic information to well established factors like lymph node status and the MAI, and may therefore be useful for designing treatment strategies in invasive breast cancer.
Renal lesions in von Hippel–Lindau disease: immunohistochemical expression of nephron differentiation molecules, adhesion molecules and apoptosis proteins
Authors: Paraf  , Chauveau  , Chrétien  , Richard  , Grünfeld  , Droz
Published: March 2003

Aims

Renal lesions in von Hippel–Lindau disease comprise clear cell simple cysts, atypical cysts and carcinomas. Although histological and molecular studies suggest that cystic lesions may represent precursors of carcinomas, there is no detailed phenotypic evidence of their relationship.

Methods and results

To investigate such a possible relationship between cystic lesions and solid carcinomas, we studied the pathological and immunohistochemical features of 328 lesions of 33 kidneys originating from 23 patients with von Hippel–Lindau disease, using a panel of antibodies directed against cytoskeleton proteins, cell surface proteins, integrin subunits, adhesion molecules, lectins, and apoptosis and proliferation markers. Solid carcinomas (n = 175) were all of clear cell type and mostly nuclear grade 1. Cystic lesions (n = 138) consisted of cystic clear cell carcinomas (n = 15), atypical cysts (n = 20) and simple cysts (n = 103). Clear cells of the simple cysts, atypical cysts and solid carcinomas coexpressed cytokeratins (CK8, CK19) and vimentin, and expressed a similar pattern of tubular markers (CD24, tetraglonolobus), integrin subunits (α3, α5, α6, αv, β1) and cell adhesion molecules (ICAM 1, VCAM 1). In all lesions studied, proliferation rate (MIB1 index) was low, and apoptosis marker expression (fragmented DNA, p53, bcl‐2) inconspicuous.

Conclusions

Phenotypic alterations found in solid renal cell carcinomas are already present in simple and atypical renal cysts of von Hippel–Lindau disease.
Adenocarcinoma of colon differentiating as dome epithelium of gut‐associated lymphoid tissue
Authors: Jass  , Constable  , Sutherland  , Winterford  , Walsh  , Young  , Leggett
Published: March 2003

Aims

An early adenocarcinoma of the ascending colon was confined to a mass of gut‐associated lymphoid tissue (GALT). The first description of an adenocarcinoma of colon differentiating as dome epithelium is presented.

Methods and results

A plaque‐like carcinoma was identified opposite the ileocaecal valve in an asymptomatic 56‐year‐old man with a family history of colorectal cancer. Malignant epithelium was confined to a mass of GALT filling but limited to the submucosa. Characterization of the neoplasm was undertaken by means of mucin histochemistry, immunohistochemistry, electron microscopy and assessment of DNA microsatellite instability status. The malignant epithelium comprised well differentiated columnar cells with a microvillous brush border and expressing MUC1, but no goblet cells or expression of MUC2. The demonstration of focal clusters of intraepithelial B‐lymphocytes supported the presence of functioning M‐cells within the malignant neoplasm. The cancer was DNA microsatellite stable despite the finding of tumour infiltrating lymphocytes.

Conclusions

There is evidence for the origin of colorectal neoplasia from dome epithelium in both experimental models and microreconstruction studies of early adenomas in nonpolypotic human colorectal mucosa. It is suggested that the lymphocyte‐rich subset of colorectal cancer that expresses MUC1 but not MUC2 may be differentiating as dome epithelium of gut‐associated lymphoid tissue.
What is the significance of muciphages in colorectal biopsies?
Authors: Salto‐Tellez M , Price A B
Published: March 2003

Muciphages (mucin‐containing macrophages), first described in 1966 by Azzopardi & Evans, are a common feature of biopsies of large intestinal mucosa, even in the absence of other abnormalities such as active inflammation or evidence of chronic inflammatory bowel disease. Should they be mentioned in diagnostic reports? Do muciphages reliably indicate previous mucosal disease, now quiescent? In the following articles, Salto‐Tellez & Price review what is known about muciphages and conclude that they reflect previous occult and clinically unimportant mucosal damage and that, in an otherwise normal colorectal mucosa, they have no diagnostic significance; and Shepherd draws attention to a wide range of clinically much more significant mucosal infiltrates that could be mistakenly regarded as muciphages and thus overlooked.
What is the significance of muciphages in colorectal biopsies?
Authors: Shepherd N A
Published: March 2003

Muciphages (mucin‐containing macrophages), first described in 1966 by Azzopardi & Evans, are a common feature of biopsies of large intestinal mucosa, even in the absence of other abnormalities such as active inflammation or evidence of chronic inflammatory bowel disease. Should they be mentioned in diagnostic reports? Do muciphages reliably indicate previous mucosal disease, now quiescent? In the following articles, Salto‐Tellez & Price review what is known about muciphages and conclude that they reflect previous occult and clinically unimportant mucosal damage and that, in an otherwise normal colorectal mucosa, they have no diagnostic significance; and Shepherd draws attention to a wide range of clinically much more significant mucosal infiltrates that could be mistakenly regarded as muciphages and thus overlooked.
Overexpression of HER2/neu in solid tumours: an immunohistochemical survey
Authors: Koeppen H K W , Wright B D , Burt A D , Quirke P , McNicol A M , Dybdal N O , Sliwkowski M X , Hillan K J
Published: March 2003

Aims:

Using a standardized immunohistochemical assay we have evaluated 575 primary neoplasms of different histogenesis to determine the incidence of HER2 overexpression in some of the most common categories of human solid neoplasms. This study addresses the variable incidence of HER2 overexpression previously published for some tumour types.

Methods and results:

The immunohistochemical staining was performed on paraffin sections of surgical specimens and a well‐defined scoring system based upon numbers of HER2 receptors expressed on the cell surface was applied. Overexpression of HER2 as defined as a HER2 score of equal or greater than 2 was seen in breast cancer (22%), pulmonary adenocarcinoma (28%), colorectal adenocarcinomas (17%), pulmonary squamous (11%) and gastric adenocarcinomas (11%). As expected, the proportion of cases with a HER2 score of 3 was highest in breast cancer. Contrary to published results prostate and pancreas adenocarcinomas showed a very low incidence of HER2 overexpression.

Conclusions:

Overexpression of HER2 is detected immunohistochemically in a proportion of epithelial neoplasms of diverse histogenesis in addition to ductal breast cancer. The standardized format of the assay will allow comparative analyses of studies performed at different institutions.
Dirofilariasis due to Dirofilaria repens in Italy, an emergent zoonosis: report of 60 new cases
Authors: Pampiglione S , Rivasi F , Angeli G , Boldorini R , Incensati R M , Pastormerlo M , Pavesi M , Ramponi A
Published: March 2003

Aims: Sixty new cases of human dirofilariasis due to Dirofilaria repens, occurring in Italy between 1990 and 1999, are presented. This is the most extensive case study of this zoonosis reported worldwide by a single study group. The aim is to utilize this large experience to characterize the different histopathological findings in the parasitic lesions in man.

Methods and results: Diagnosis was performed on histological sections of the nematode enclosed in the nodules excised at biopsy or surgery. The nematode was located in the subcutaneous tissue (49 cases), the epididymis (two cases), the spermatic cord (two cases), the lung (two cases), the breast (two cases), the omentum (two cases) and under the conjunctival tissue (one case). The majority of cases (46) were from Piedmont; the remainder were from Emilia‐Romagna, Sardinia, Sicily, Tuscany, Apulia and Lombardy. The histopathological features of the lesions are described and the clinical and epidemiological aspects of the zoonosis are discussed. The prevalence in Italy in general and in the area of Piedmont in particular, comprising the provinces of Alessandria, Asti, Novara and Vercelli, which is one of the most severely affected areas of the world, is emphasized. The evident increase in the number of cases in the last few years is a clear indication that it is an emergent zoonosis.

Conclusions: We recommend that each and every case observed be recorded, to enable the true extent of human dirofilariasis in Italy to be assessed, and that a reference centre be set up in the area to collate the data. The importance of the histopathologist's role in the diagnosis is stressed.
Pathology of lymphoma progression
Authors: Müller‐Hermelink H K , Zettl A , Pfeifer W , Ott G
Published: March 2003

Reflecting the stepwise process of oncogenesis, lymphomas may cumulatively develop a more aggressive phenotype during the course of disease, a process referred to as lymphoma progression. Although morphological, clinical and biological aspects of lymphoma progression do not always overlap, changes in lymphoma morphology frequently indicate alterations in the clinical and biological behaviour of the disease. Indolent and aggressive lymphomas in disease progression can either be clonally related or represent clonally unrelated neoplasms. We propose to use the term ‘lymphoma progression’ in a biological sense denoting only clonal development of and within a lymphoma entity. The term ‘composite lymphoma’ should be used as a merely descriptive morphological designation for different lymphoma entities in one individual irrespective of clonal relationship. Many types of aggressive B‐cell non‐Hodgkin's lymphomas and Hodgkin's lymphomas are reported to secondarily develop in lymphoma progression. Genetic changes associated with lymphoma progression frequently abrogate the differentiating effects of alterations occurring in indolent lymphomas, leading to increased cell proliferation. Within different lymphoma entities, high‐risk disease variants mimicking lymphoma progression exist.
Pulmonary artery dissection in patients without underlying pulmonary hypertension
Authors: Inayama Y , Nakatani Y , Kitamura H
Published: March 2003

Pulmonary artery dissection in patients without underlying pulmonary hypertension

Aims: Pulmonary artery (PA) dissection is a rare event which usually occurs in patients with underlying pulmonary hypertension. We describe two patients who developed PA dissection without pre‐existing pulmonary hypertension and present an extensive review of the literature.

Methods and results: In the first patient (a 59‐year‐old woman), acute‐onset dyspnoea was initially thought to have been caused by pulmonary thrombosis, and thromboendarterectomy was performed. Histologically, pulmonary dissection without external rupture was evident, chiefly in the right main PA. In the second patient, an 85‐year‐old man who had hypergammaglobulinaemia of unknown cause and died from a haemorrhagic gastric ulcer, arterial dissection was detected at autopsy. There was no underlying pulmonary hypertension in either patient. Although the true reason for the development of dissection is unclear, pre‐existing inflammation was considered to be related to its formation, at least in the second case.

Conclusions: A literature review indicated that idiopathic and inflammation‐related PA dissection is extremely unusual. Since PA dissection is very rare, it is important to be aware of its features in order to make a correct diagnosis.