[The role of human papillomavirus in cyto-histological practice: distribution and prevalenceof hig-risk strains (16, 18, 31, 33, and 35) in intraepithelial lesions and neoplasia of the uterine cervix]. / Il ruolo del papillomavirus umano (HPV) nella pratica cito-istologica: distribuzione e prevalenza dei ceppi ad alto rischio (16, 18, 31, 33 e 35) nelle lesioni intraepiteliali e nelle neoplasie della cervice uterina.

INTRODUCTION: Many studies have already shown the association of persistent infection of human high risk papillomavirus (HPV) with the development of pre-invasive and invasive cervical disease. MATERIALS AND METHODS: We evaluated the use of high risk HPV testing in a study of about 1908 women, aged 29-78, who attending, from 1996 to 1998, the Sant'Anna Hospital in Turin for routine, second level smears and histopathological diagnosis. We considered all cervical lesions: ASCUS, LSIL, HSIL, squamous and adeno invasive cancers. HPV testing was performed by polymerase chain reaction (PCR) using L1 consensus primers which can detect almost all infections (high and low risk types). The most important high risk HPV types (16, 18, 31, 33 and 35) were tested using specific primers. RESULTS: The prevalence of high risk HPV was: ASCUS 42.2%, LSIL 39%, HSIL 73.5%, squamous invasive cancers 98.3% and adeno 100%. In addition HPV 16 is the most represented type in all lesions: ASCUS 40%, LSIL 62%, HSIL 71.2% squamous invasive cancers 73.3% and adeno 50.6%. In addition we study the mean age of cervical cancer onset compared with the different high risk HPV types. We found that HPV 18 related cancer occurs in younger women (mean age 41 years; range 39-42). CONCLUSIONS: The addition of high risk HPV testing to cytology may improve early identification of women at risk for cervical cancer.

Role of fine-needle aspiration biopsy in breast lesions: analysis of a series of 4,110 cases.

From January of 1990 to December of 1992, 6,954 consecutive cytologic breast fine-needle aspiration biopsies (FNAB) were performed at the Laboratory of Pathology of Sant'Anna Hospital in Turin. Of these cases 62% were solid nodes, 35% were cystic nodes, and 2.7% were nonpalpable breast lesions (stereotaxic or ultrasound guided FNAB). We verified 4,110 cases: 913 cases underwent surgery and 3,197 were evaluated clinically, and/or cytologically, and/or with mammography at least 1 yr after the first diagnosis, or checked with the database of the Tumor Registry of Turin. In our series the FNAB sensitivity was 94.6%, specificity was 99.9%, accuracy was 98.8%, inadequate samples were 6.4%, false-negative rate was 1.4%, and false-positive rate was 0.3%. Our results indicate that the use of cell block improves sensitivity (from 85.2 to 94.6%) and strongly reduces false-negative results (from 3.9 to 1.4%). We conclude that FNAB is a discriminant procedure to the surgical biopsy in cases with clinical, ultrasound, or mammographic low or intermediate suspect, contributing to allow a high malignant/benign surgical biopsy rate and to reduce the need for frozen section diagnosis and medical costs.

[Lymphadenopathy caused by Toxoplasma in an intramammary lymph node: role of molecular biology in the diagnosis]. / Linfoadenopatia da Toxoplasma in linfonodo intramammario: ruolo della biologia molecolare nella diagnosi.

We describe a case of Toxoplasma gondii lymphoadenopathy in an intramammary lymph node in a 22 year old woman. Clinical evidence and ultrasound were suggestive for fibroadenoma, while cytology on fine needle aspiration suspected a lymphomatous lesion. The pathological examination demonstrated a lymph node with granulomatous foci with epithelioid histiocytes, consistent with Toxoplasma gondii lymphadenopathy. The pathological finding was confirmed by serological tests and by PCR (Polymerase Chain Reaction) using specific primers designed on ribosomal 18s DNA sequence of Toxoplasma gondii. The aim of this work is to emphasize the role of molecular biology techniques as an aid to pathological diagnosis in parasite diseases.

An intronic deletion in TP53 gene causes exon 6 skipping in breast cancer.

Six hundred and thirty primary breast cancer were screened for abnormalities in exons 5, 6, 7 and 8 of the TP53 tumour suppressor gene. Analysis of the structure of the TP53 gene exons was performed with the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) method and with direct sequencing of amplified DNA. In a breast tumour case from a postmenopausal patient, we found a deletion of 36 bp in intron 5 and no immunohistochemical staining for p53. We amplified and sequenced the cDNA region between exons 4 and 7 and showed that the deletion causes the skipping of exon 6. The resulting mRNA sequence had a frameshift that yields an inactive protein with a truncated C terminus. These results show the first example of intronic deletion causing exon skipping at the TP53 gene level.

Extraskeletal Ewing's tumor with translocation t(11;22) in a patient with Down syndrome.

A case of a small cell malignant tumor that occurred in the soft tissues of a 16-year-old boy with Down syndrome (47,XY,+21) is reported. The histologic and histochemical patterns were consistent with an extraskeletal Ewing's sarcoma (ES). The cytogenetic analysis of the tumor cells showed a t(11;22)(q24;q21), tetrasomy of chromosome 21, and trisomy of chromosome 14. The observation of a t(11;22) in an ES gives credit to the morphologic evidence in favor of the common (probably neuroectodermal) origin of the skeletal and extraskeletal forms of Ewing's sarcoma (ES). The possible pathogenetic significance of the constitutional trisomy of chromosome 21 in determining the occurrence of this tumor is discussed.

Fine-needle aspiration of breast lesions: role and accuracy in a review of 7,495 cases.

In the past 10 years, 7,495 cytological breast fine-needle aspirations (FNAs) were performed (4,756 FNAs of solid nodes and 2,739 of cystic nodes). Of these, 2,099 cases underwent surgery; 650 (31%) had histologically proven carcinoma. Sensitivity was 83.9%, specificity was 99.5%, the predictive value for negative results was 93.2% and for positive results was 98.6%, and the accuracy was 94.6%. Inadequate (13.3%) and doubtful samples (8.1%) were excluded from calculation. False-negative results (82 cases) mainly resulted from sampling errors. False suspicious results (six cases) lessened with increasing experience in breast pathology and with the application of strict diagnostic criteria, but most likely they will never reach zero. Frozen-section diagnosis could be bypassed only in selected cases. Guidelines on the role of FNA in management of solid breast lesions are given. FNA deserves further evaluation in diagnosing early stages of breast carcinoma: sensitivity was 7.5% in 57 carcinomas in situ, 67.5% in 55 minimally invasive carcinoma, and 92.7% in 538 nonminimally invasive carcinomas.

Primary choriocarcinoma of the fallopian tube: report of a case.

A case of the relatively rare condition of a choriocarcinoma in the fallopian tube is presented. The patient apparently recovered completely and quantitative beta hCG assay demonstrated negative results after TAHBSO and adjuvant chemotherapy. This brings the total cases reported to 77.

Accuracy of frozen section diagnosis in breast cancer detection. A review of 4436 biopsies and comparison with cytodiagnosis.

Frozen section diagnosis (FSD) given in 4436 consecutive breast biopsies performed in 5 years in a single pathology laboratory were checked against the final pathological report. In 4284 cases (96.57%) there was no difference between the FSD and the definitive diagnosis. There were 74 (1.66%) false negative reports and no false positive diagnoses. The diagnosis was deferred to paraffin sections in 78 cases (1.75% of biopsies). The predictive value for positive results was 100% and for negative results 97.5%; the specificity was 100%, the sensitivity 94.6% and the accuracy 98.3%. Minimal breast cancer, in situ (CIS) especially, was the main source of false negative reports. In non minimal invasive cancers (NMIC) FSD was correct in 99.42%. In minimal invasive cancers (MIC) FSD was correct in 80.21%, false negatives and deferred diagnosis increased to 8.79% and 10.98%. In CIS false negatives increased to 76.82% and deferred diagnoses to 12.19%. The sensitivity of fine needle aspiration, performed before biopsy in a portion of the patients, was lower than FSD in NMIC (71.39% versus 99.21%) and in MIC (41.66% versus 80.55%), identical to FSD in CIS (7.40% versus 7.40%). The value of cytodiagnosis in addressing surgery is discussed.

Lactating supernumerary mammary gland tissue in the vulva.

2 cases of supernumerary breast tissue in the vulva observed in pregnant women are reported. The mammary tissue showed histological features typical of the lactating breast and immunohistochemical evidence of milk protein production.

Juvenile milk protein secreting carcinoma.

A case of juvenile secretory carcinoma of the breast is reported. The tumor occurred in a 19 yr-old nulliparous woman and was treated by local resection; it recurred 7 years later. Slight infiltration of the pectoral muscle, metastatic involvement of one lymph node and multifocal areas of carcinoma were found at radical mastectomy. No further recurrence has been detected after 1 year. This case confirms the slow evolution of this neoplasm but stresses that its behavior is not always as indolent as previously believed. We have used histochemical techniques for mucins (PAS, Alcian Blue) and immunoperoxidase methods for milk proteins (MFGM, beta-Casein, alpha-lactalbumin), for myoepithelial cells (actin) and for oncofetal antigens (CEA). Our results suggest that: Immunoperoxidase methods for milk proteins are a more specific and reliable marker than PAS staining in characterizing the secretory activity of juvenile carcinoma. The absence of myoepithelial cells in infiltrative areas detected by immunoperoxidase methods for actin confirms the low degree of organization in this well differentiated carcinoma of limited aggressiveness which secretes milk proteins.

Radiosurgical treatment of uterine cervix carcinoma at the 1st Clinic of Obstetrics and Gynecology of the University of Turin, (in the period 1972-1978).

The Authors report the results of a planned prospective study on Radiosurgical treatment of carcinoma of the cervix at stage Ia, Ib, and IIa. The protocol adopted is based on preoperative Curietherapy performed by Ir192 on a after loading technique device, hysterectomy according the Wertheim-Meigs' technique with systematic lymphadenectomy for the internal and external iliacs and obturator stations, Telecobalt therapy in cases with hystological evidence of lymphatic spread. The Authors discuss the results after three and five years in term of survival according to stage and type of treatment, the anatomosurgical examination and the histologic findings of the lymph nodes. At the end, they analysed the complications according to the stage and the kind of treatment, studying only recovered patients and performing the analysis after three years, in order to allow all complications to appear.

Hormone patterns during bromocriptine-induced pregnancy in hyperprolactinemic patients.

Plasma prolactin (PRL) and human placental lactogen (HPL), and urinary estriol and pregnanediol were studied during pregnancies induced with bromocriptine (Parlodel, Sandoz) in 10 cases of hyperprolactinemia. Previous selective adenomectomy or intrasellar implantation of radioactive gold (198Au) failed to induce a complete remission in 3 of these subjects. PRL rapidly increases after bromocriptine withdrawal, reaching values higher than those in normal women in the same stage of pregnancy within a few weeks. At term, pathological PRL levels occurred in 3 subjects only (with distinct alterations of the sella turcica). Estriol, pregnanediol and HPL were normal in all cases. These findings suggest that PRL levels higher than those normally observed during pregnancy do not alter fetoplacental endocrine function.