Specificity of the 5q-chromosome in a distinct type of refractory anemia.

A further instance of the 5q-chromosome associated with a distinct type of aregenerative anemia strengthened the hypothesis of specificity and consistency of this karyotypic abnormality in a new hematologic entity. The Giemsa banding technique revealed that the deletion of the long arms of chromosome number 5 was interstitial: del (5) (pter leads to q12 : : q31 leads to qter).

Chorangiocarcinoma: an unusual tumour of the placenta. The missing link?

A tumour occurring in an otherwise normal placenta presented the vascularity of a mature chorangioma but was surrounded by a neoplastic trophoblastic proliferation. A chorangioma with an atypical associated trophoblastic proliferation has never been reported in any of nearly 500 cases of chorangiomas described in the literature. The possibility of a combined lesion (for which we propose the term chorangiocarcinoma) is emphasized. It cannot be excluded however that chorangiomas could be, in rare cases, true neoplasms rather than hamartomas.

Evidence of human papilloma virus infection but lack of Epstein-Barr virus in lymphoepithelioma-like carcinoma of uterine cervix: report of two cases and review of the literature.

Lymphoepithelioma-like carcinoma (LELC) of uterine cervix is an uncommon variant of squamous cell carcinoma (SCC). We report here 2 new cases in which DNA sequences from human papilloma virus (HPV) types 16 and 18 were detected by polymerase chain reaction (PCR). To the best of our knowledge, HPV infection has not been previously described in similar cases occuring in European women. Moreover, Epstein-Barr virus (EBV), which is frequently associated with cervical LELC in Asian women, was absent in our 2 cases. These results suggest that HPVs but not EBV can play a role in the pathogenesis of LELC occuring in women originating from Western countries.

Computerized morphonuclear characteristics and DNA content of adenocarcinoma of the pancreas, chronic pancreatitis, and normal tissues: relationship with histopathologic grading.

We report the morphonuclear characteristics of normal (13 cases), benign (ie, chronic) pancreatitis (six cases), and neoplastic (ie, ductal) adenocarcinoma (22 cases) tissues of the pancreas. This description is based on computerized cell image analysis, which permits the determination of parameters related to the morphometric (nuclear area), densitometric (nuclear DNA content), and chromatin texture features of Feulgen-stained nuclei from paraffin-embedded archival material. We observed that nuclear area discriminates between normal and benign (ie, chronic pancreatitis) as opposed to neoplastic cell nuclei. Morphonuclear parameters describing chromatin pattern characteristics made it possible to discriminate between grade I pancreatic carcinoma and normal and benign cell nuclei on the one hand, and grades I and III carcinoma on the other hand. The nuclear DNA content increased in a continuous manner from normal and benign through low-grade to high-grade neoplastic tissues of the pancreas. Combining the morphometric, densitometric, and textural parameters into one equation, we were able to calculate a score (ie, the malignancy level index) that showed a close relationship to conventional histopathologic grading. Thus, the computer-aided diagnosis of cytologic specimens from pancreatic lesions offers information of the same significance as that obtained by conventional histopathologic grading.

Detection of bronchial preneoplastic lesions and early lung cancer with fluorescence bronchoscopy: a study about its ambulatory feasibility under local anaesthesis.

BACKGROUND: Autofluorescence bronchoscopy (AB) enhances the bronchoscopist's ability to diagnose bronchial preneoplastic lesions and early cancer. We undertook a study to assess its feasibility and performance under local anaesthesia on a real ambulatory mode. METHODS: Thirty-four consecutive patients at very high risk for lung cancer were prospectively studied by AB under local anaesthesia, without any sedation. Lidocaine doses, time, oxygen saturation, peak expiratory flow (PEF) and the number of cough episodes were measured. Continuous assessment of the respiratory sensation was obtained with a visual analog scale. A total of 172 biopsies were performed in abnormal and normal areas. RESULTS: The procedure was long-lasting (mean +/- SD: 26.6 +/- 6.0 min), required high total doses of Lidocaine (660 +/- 107 mg) without any significant side effect, and was associated with significant decreases in O2 saturation from 98.5 +/- 1.4 to 96.1 +/- 2.5% and in PEF from 380 +/- 96 to 310 +/- 78 l/min. However, the cough counts were moderate and the majority of patients reported no respiratory discomfort. 62 hyperplasia, metaplasia, dysplasia and carcinoma in situ (CIS) were detected and the relative sensitivity of AB +/- white-light bronchoscopy (WLB) versus WLB alone was 3.75 for intraepithelial lesions corresponding to moderate dysplasia or worse. CONCLUSIONS: AB, a procedure that increases our ability to recognize preneoplastic lesions and early lung cancer, can be performed under local anaesthesia, without systemic sedation in patients at very high risk for lung cancer.

Complete remission following donor PBSC after low-dose cytarabine chemotherapy for early relapse of acute myelogenous leukemia after allogeneic stem cell transplantation.

A 55-year-old woman with chemotherapy-resistant acute myeloblastic leukemia (AML M2) relapsed 3 months after allogeneic PBSC transplant. The patient was treated with two cycles of low-dose cytarabine chemotherapy followed by G-CSF mobilized donor PBSC after cessation of all immunosuppressive treatment. Hematological and cytogenetic complete remission was observed after the first cycle. The patient had been previously treated for AGVHD after allogeneic PBSC transplantation and experienced a second AGVHD after the second cycles of cytoreductive treatment and donor PBSC infusion. Hematological recovery after donor PBSC infusion was faster than recovery after previous chemotherapy or high-dose chemotherapy. During treatment no febrile neutropenia was observed. This case shows that donor PBSC infusion cannot only provide prolonged complete hematological and cytogenetic remission but also seems to support accelerated hematopoietic recovery for some patients relapsing after allogeneic BMT.

Nuclear DNA content, proliferation index, and nuclear size determination in normal and cirrhotic liver, and in benign and malignant primary and metastatic hepatic tumors.

The distribution values of ploidy, of the proliferation index, of the percentages of diploid cells/case, of nuclear size, and DNA histogram type are described in a series of 92 liver samples from 87 patients. The 92 samples include normal (31 cases) and cirrhotic (14 cases) tissues, benign tumors (7 cases), well-differentiated hepatocellular carcinomas (HCCs, 13 cases), moderately and poorly differentiated HCCs (8 cases), and colorectal glandular metastatic tissues (19 cases). The samples are from either fine-needle aspiration biopsy (FNAB) or histologic imprint smears (HIS). Nuclear assessments were computed on Feulgen-stained nuclei by means of a cell image processor. The results show that the mean DNA index value, the mean nuclear area (NA) value, and the mean percentages of diploid cells per sample are significantly different in the three benign groups under study (normal and cirrhotic tissues and benign tumors) as compared with the mean parameter values from the three neoplastic liver groups (well-differentiated and poorly differentiated HCCs and colorectal metastases). None of these three parameters, however, makes it possible to discriminate clearly between these six histopathologic groups at the individual case level. The mean proliferation index values were significantly lower in the normal tissues and the benign tumors than in the four other histopathologic groups. Recognizing six DNA histogram types, ie, diploid, hyperdiploid, triploid, hypertriploid, tetraploid, and polymorphic, we observed that all the benign samples (the normal and cirrhotic tissues and the benign tumors) exhibited a diploid and/or tetraploid DNA histogram pattern, whereas the neoplastic samples exhibited the six DNA histogram patterns. The combination of the five computerized parameters into a cytologic score (CS) ranging from 5 to 15 permits clear-cut discrimination between nonneoplastic and neoplastic liver cases. The specificity and sensitivity, and the positive and negative predictive values relating to this score were as high as 100%, 95%, 100%, and 96%, respectively.

Sensitivity of HER-2/neu antibodies in archival tissue samples of invasive breast carcinomas. Correlation with oncogene amplification in 160 cases.

Overexpression and amplification of the HER-2 oncogene in patients with breast cancer has correlated with early onset of metastasis, resistance to hormonal therapy and some forms of chemotherapy, and shortened survival. Therefore, evaluation of this putative prognostic or predictive factor seems critical. Because different antibodies are used for the detection of the 185-kd HER-2 oncoprotein, we studied the sensitivity of 3 frequently used antibodies. Immunohistochemistry results were correlated with gene amplification level as assessed by fluorescence in situ hybridization. Protein overexpression was found in 17.2% and 12.5% of cases using antibodies against the external (TAB250) and internal (CB11) domains of the protein, respectively, and in 38.0% of cases using a rabbit polyclonal antibody. Fluorescence in situ hybridization was successful in all 160 tumors, and amplification was found in 37 tumors (23.1%). The monoclonal antibody TAB250 had the lowest misclassification rate, 9.6% (sensitivity, 67%; specificity, 97.5%).

Chromosome 6 trisomy as sole anomaly in a primary Merkel cell carcinoma.

We present a case of Merkel cell carcinoma of the thigh diagnosed by conventional histology, immunohistochemistry, electron microscopy and cytogenetics. A unique chromosome 6 trisomy characterized this primary neoplasm, as confirmed by FISH study. The role of chromosome analysis and interphase cytogenetics is emphasized as an adjunct in the subtyping of tumours and their prognostic evaluation.

Reliability of the tissue microarray based FISH for evaluation of the HER-2 oncogene in breast carcinoma.

AIMS: Tumour tissue microarray allows the analysis of hundreds of tumour samples simultaneously on a single microscope slide. However, the extremely small tissue samples taken from the original tissue may not always be representative of the entire tumour. METHODS: The reliability of this new technology was investigated by analysing HER-2 oncogene amplification by fluorescence in situ hybridisation (FISH) from representative slides of the whole tumour and small tissue core biopsies from 29 invasive breast tumours. RESULTS: The tissue microarray method had high accuracy; in only one of 29 cases (3.4%; 95% confidence interval, 0% to 10%) were the results discordant with whole tumour analysis. CONCLUSION: Tumour microarray is a highly reliable method for analysing HER-2 oncogene amplification by FISH in human breast tumours.

Trisomy 11 in preleukemia.

The clinical and cytogenetic findings of a patient with a preleukemic state and trisomy 11 are reported. Trisomy 11 was present as the sole karyotypic alteration at the time of overt leukemia. Trisomy 11 presents an additional chromosomal abnormality not previously described in preleukemia.

A unique clonal chromosome 2 deletion in endomyometriosis.

The cytogenetic analysis of a short-term culture from a so-called endomyometriosis revealed a unique clonal del(2)(p21). The embryologic origin of this uterine-like mass is controversial. The finding of a clonal chromosome aberration favors the proliferation hypothesis and suggests that endomyometriosis is a true neoplasm and that a somatic mutation might be involved in the etiology of this lesion.

Leukemia in a trisomy 21 mosaic: specific involvement of the trisomic cells.

Acute monoblastic leukemia was diagnosed in a 32-month-old boy with mild signs of Down's syndrome. Chromosome analysis of cultured skin fibroblasts and peripheral blood lymphocytes disclosed a constitutional mosaicism (46,XY/47,XY,+21). At initial diagnosis of acute leukemia, additional chromosomal changes were found in bone marrow blasts that were consistent with the M5 subtype. The cytogenetic markers of the acute leukemia were restricted to the trisomic subset and disappeared during remission. These findings add further weight to the suggestion that the propensity of Down's syndrome patients to develop leukemia is directly related to their karyotype abnormality and that leukemia might be clonal in origin.

Translocation (6;16) in a case of granulosa cell tumor of the ovary.

We performed a cytogenetic study of an ovarian granulosa cell tumor (GCT). Tumor cells showed a translocation (6;16); the full karyotype was 45,XX-6,dic(6;16)(q11;q22)/44,XX,-6,-22,dic(6;16)(q11;q22),-22/46,XX,- 6,dic(6;16)(q11;q22), +dic(6;16)(q11;q22). This is the second case of GCT with structural changes of chromosome 6 leading to loss of 6q material.

Trisomy 21 as the sole abnormality in a refractory anemia with ring sideroblasts.

Numerous chromosome abnormalities have been described in myelodysplastic syndromes, but single karyotypic aberrations are much less frequent. We report the case of a 65-year-old woman who presented a trisomy 21 as the sole karyotypic anomaly for a refractory anemia with ring sideroblasts. The nature of such an anomaly is discussed in regard to pathogenesis and prognosis.

Transitional cell carcinoma of the bladder: evaluation of the role of human papillomaviruses.

OBJECTIVES: The study evaluated the conflicting results of the role of human papillomavirus (HPV) in the development of bladder carcinoma. METHODS: We analyzed the frequency of HPV types 6, 11, 16, 18, and 33 by using polymerase chain reaction on formalin-fixed, paraffin-embedded specimens, from 75 cases of transitional cell carcinoma (TCC) of the bladder. Fifteen samples of normal urothelium adjacent to TCC (10) or from normal bladder obtained at autopsy (5) served as negative controls. RESULTS: HPV type 16 deoxyribonucleic acid (DNA) was detected in 2 (2.7%) of the 75 cases of TCC and in none of the normal urinary bladder cases. The 2 patients with HPV type 16 were immunosuppressed after undergoing renal and cardiac transplantation. CONCLUSIONS: These results strongly suggest that HPVs play a minor role in the development of TCC of the bladder in the general population, although they can act as oncogenic agents in predisposed patients, such as those who are immunosuppressed.

Expression of p53 in preneoplastic and early neoplastic bronchial lesions.

p53 alteration has been reported to be an early event in bronchial carcinogenesis. Our study purpose was to determine the rate of p53 expression in the various preneoplastic and early neoplastic bronchial lesions obtained by biopsy during fluorescence bronchoscopy and to analyse its association with patients characteristics. Various stages of preneoplastic lesions as well as radio-occult lung cancer were studied in biopsies obtained by fluorescence bronchoscopy. We assessed the expression of p53 by immunohistochemistry using monoclonal antibody clone DO7. The p53 expression was considered as positive if > or = 1% of cells were positive and the level of positivity was expressed in percentage of positive cells. Fourteen patients were included in each category of preneoplastic lesions. At the threshold of 1% of positive cells p53 expression was observed in 28.5% of the patients with a histologically normal epithelium. This number of positive patients increased with the severity of preneoplastic lesions and reached 100% in the mild dysplasia. The mean rates of p53 positive cells for normal epithelium, hyperplasia, metaplasia, mild and severe dysplasia, carcinoma in situ and invasive radio-occult carcinoma were respectively 0.9, 3.4, 9.1, 20.5, 50.2, 34.7 and 42.5%. There was no statistically significant correlation between p53 expression and patient characteristics such as sex, age, smoking habits and indication for fluorescence bronchoscopy. The alteration of p53 expression in patients with high risk of lung cancer was an early event: this abnormality increased with the severity of the lesions, without significant correlation with patient characteristics.

Locoregional recurrences after 649 modified radical mastectomies: incidence and significance.

A continuous series of 649 patients, treated by modified radical mastectomy for primary breast carcinoma, is analyzed after a median follow-up of 92 months. 'True isolated' locoregional recurrences (LR), defined as LR not preceded or followed by distant metastases within 6 weeks, appeared with a cumulative actuarial incidence rate of 6%, 14% and 19% after 1, 5 and 7 years respectively, whereas the respective figures for distant metastases (M1) were 10%, 37% and 48%. The main initial parameters, predicting both the LR-free and the M1-free interval, are presented by statistical analyses in the following order of importance: number of invaded lymph nodes in the axilla, tumor size (T) and histological grading of differentiation. The same factors also predicted the imminence of M1 once LR had occurred, as well as survival after LR. A higher incidence of M1 after LR was also correlated with estrogen-receptor negative tumors and with those LR occurring within one year after mastectomy. LR occurred at the chest wall (65%), in the sub-clavicular fossa (16%) and the axilla (6%); the remaining 13% occurred in two of the sites. There was a trend towards longer survival after chest wall recurrence than after LR recurrence at another site. Axillothoracic irradiations postmastectomy gave a lower rate of LR in 227 patients than did a regimen of 12 months adjuvant chemotherapy with irradiation restricted to the internal mammary lymph nodes in 120 subsequent patients: 17 vs 25% at 5 years (P = 0.03 when adjusted by initial nodal involvement and T-size). Total excision of LR (repeated if new LR occurred) gave better rates of local ultimate control and survival than other kinds of treatments, with or without adjuvant local or systemic therapy. LR is not always a sign of imminent generalized disease. Actuarial 5-year survival after LR is 26.2% overall whereas, if only 'true isolated' LR are considered, the survival is 37%.

Expression of thrombospondin in non-small cell lung cancer.

OBJECTIVE: Initially considered as an inhibitor of angiogenesis, the role of thrombospondin is currently controversial. The primary purpose of our study was to determine the expression of thrombospondin (TSP) in invasive lung tumours. The secondary objectives were to investigate its relationship with other factors related to angiogenesis and to assess their clinicopathological significance. MATERIALS AND METHODS: From January 1993 to September 1998, we collected non-small cell lung cancer (NSCLC) and normal nearby-matched tissues from surgical specimens of 64 patients. Using these specimens, we assessed the expression of TSP by immunohistochemistry with monoclonal antibody to human TSP (clone 11.4). This expression was also correlated with other factors directly or indirectly related to angiogenesis:p53, Ki-67 as proliferation factor and microvessel count determined with anti-CD-31 antibody. RESULTS: The resected tumours (stages I-IIIB) consisted of 30 adenocarcinomas, 24 squamous cell carcinomas, 5 bronchioalveolar carcinomas, 4 adenosquamous carcinomas and 1undifferentiated NSCLC. The mean values of TSP expression in neoplastic and normal related tissues were 63.08% and 86.57 %, respectively. This difference was statistically significant (p = 0.02). There was a higher level of variability of TSP expression between tumours than between normal tissues. The expression of TSP in NSCLC was statistically correlated to the expression of TSP in normal matched tissues (coefficient correLation rate = 0.31, p<0.01). The median expression of p53, Ki-67 and microvessel count in tumours was 45.00%, 38.80% and 8.33%, respectively. The correlations between TSP and the other biological variables and between these latter variables themselves were not statistically significant. No statistically significant difference was observed in survival according to TSP expression. CONCLUSION: TSP appeared to be decreased in NSCLC in comparison with normal matched tissue. The TSP expression was not correlated with the other studied variables and was not associated with a significant difference in survival.

Complete hydatidiform mole and coexisting normal fetuses. A report of two cases with contrasting outcomes.

BACKGROUND: Multiple pregnancies consisting of a complete hydatidiform mole and coexisting fetuses are relatively rare but may become more common due to the increasing use of ovulation-induction agents. CASES: We report on a twin and a triplet pregnancy, conceived using clomiphene citrate, with contrasting outcomes. The twin pregnancy resulted in a term delivery of a healthy singleton and the triplet pregnancy in a termination at 17 weeks followed by the development of choriocarcinoma. CONCLUSION: The few cases available suggest that a subgroup of complete moles follows a more benign course and can be managed conservatively, allowing the pregnancy to go to term with appropriate follow-up, whereas other cases follow a more aggressive course. Larger case series are needed to develop definitive protocols.