The risk of misinterpreting genital signs of sexual abuse in cadavers: a case report.

The significance of genital findings in a case of suspected child sexual abuse has been widely debated in the past decades, as shown by the different classifications available in literature. In the case of postmortem examination, the search for signs of sexual abuse is considerably more difficult because of the superimposition of postmortem modifications, which may determine tissue modifications that can be mistaken for traumatic lesions. This study aims at reporting a case where presumed findings of the first autopsy were denied by histological analysis; in detail, what looked like a possible bruise of the hymen was correctly recognized as hypostasis (livor) of the hymenal tissue by histological analysis. This case report suggests caution in the analysis and discussion of genital lesions found during postmortem examination since the superimposition of cadaveric modifications may radically modify the morphology of soft tissues.

Sudden death from systemic sarcoidosis: a case of legal medicine.

INTRODUCTION: The sarcoid condition of vital organs such as heart, lungs, liver and brain, may constitute, though rarely, a dangerous situation for survival. In forensic pathology, sudden death related to such disease represents an unusual event occurring in subjects who die unexpectedly in spite of their previous good health, and whose autopsy reveals, mainly, the involvement of heart or the central nervous system (CNS). THE CASE: The Authors describe a case of sudden death due to systemic sarcoidosis with atypical presentation in a young South American nulliparous woman showing, as the only symptom, occasional episodes of spotting during the last two months of her life. RESULTS: The only noteworthy finding from the autopsy resulted in secondary obstructive hydrocephalus. The subsequent forensic toxicological examination was negative, whereas the histopathological examination, conducted by means of post-fixation techniques and standard coloring methods on the viscera removed during autopsy, revealed useful data to determine the cause of death, consisting of a diffuse inflammatory reaction with giant cells and epithelioid cells of sarcoid type localized in the CNS and in the genitourinary apparatus. CONCLUSIONS: The case presented, ranking among deaths occurred unexpectedly, is a useful opportunity both for clinical remarks, given its inherent diagnostic difficulties, especially in the presence of atypical symptoms, and for legal medicine ones, given the inclusion of sarcoidosis in cases of sudden death that can give rise to criminal investigations.

The use of the anti-Glycophorin A antibody in the detection of red blood cell residues in human soft tissue lesions decomposed in air and water: a pilot study.

The distinction between antemortem and postmortem wounds is one of the most important medico-legal problems. In fresh cadavers the macroscopic examination of haemorrhagic infiltration can be sufficient to reveal the vitality of a wound but in more difficult cases (putrefied corpses) histological and histochemical analyses need to be performed. The scope of this study was to detect the vitality of soft tissue samples in an advanced state of putrefaction using a monoclonal anti-human Glycoforin A antibody in order to evaluate the presence of red blood cells or red blood cell residues. Samples of skin wounds were taken from cadavers with a known time survival between trauma and death, and then submitted to a simulated putrefaction procedure. The skin samples were left to decompose for 30 days in air and in water and analyzed at a time interval of 3-6-15-30 days. These samples were stained with haematoxylin eosin stain, trichrome stain and with immunohistochemical stains. Results showed that in the air red blood cells could be seen for up to six days and granular deposits of Glycophorin reactive material for up to 15 days whereas no red blood cells were recognizable after 30 days. In water red cell putrefaction (or non-detection) was faster than in the air: after six days only amorphous granular deposits slightly reactive to Glycophorin could be seen. Nonetheless results showed that extravasated red blood cell residues can still be detected in skin bruises left to decompose in air and water, for up to at least 15 days in the open air and one week in water.

PI3KCA/PTEN deregulation contributes to impaired responses to cetuximab in metastatic colorectal cancer patients.

BACKGROUND: It has been reported that KRAS mutations (and to a lesser extent KRAS mutations with the BRAF V600E mutation) negatively affect response to anti-epidermal growth factor receptor (EGFR) mAbs in metastatic colorectal cancer (mCRC) patients, while the biological impact of the EGFR pathway represented by PI3K/PTEN/AKT on anti-EGFR treatment is still not clear. PATIENTS AND METHODS: We analysed formalin-fixed samples from a cohort of 32 mCRC patients treated with cetuximab by means of EGFR immunohistochemistry, EGFR and PTEN FISH analysis, and KRAS, BRAF, PI3KCA, and PTEN genomic sequencing. RESULTS: Ten (31%) of 32 patients showed a partial response to cetuximab and 22 (69%) did not [nonresponder (NR)]. EGFR immunophenotype and FISH-based gene status did not predict an anti-EGFR mAb response, whereas KRAS mutations (24%) and PI3K pathway activation, by means of PI3KCA mutations (13%) or PTEN mutation (10%)/loss (13%), were significantly restricted to, respectively, 41% and 37% of NRs. CONCLUSION: These findings suggested that KRAS mutations and PI3KCA/PTEN deregulation significantly correlate with resistance to cetuximab. In line with this, patients carrying KRAS mutations or with activated PI3K profiles can benefit from targeted treatments only by switching off molecules belonging to the downstream signalling of activated EGFR, such as mammalian target of rapamycin.

Lethal cardiac amyloidosis: Modification of the Congo Red technique on a forensic case.

Congo Red staining is usually used in diagnosing amyloidosis, a pathology characterized by the storage of abnormal proteins in several human organs. When assessed on samples fixated in formalin and embended in paraffin, this staining can undergo several artefacts, causing diagnostic and interpretative difficulties due to its weak stainability and a consequent reduced visibility of the amyloid. These complications, in time, requested several variations of this staining technique, especially in clinical practice, while in the forensic field no protocols has ever been adapted to cadaveric samples, a material that is already characteristically burdened by a peculiar stainability. In our work, studying a sudden death caused by cardiac amyloidosis and diagnosed only with post-mortem exams, we present a modified Congo Red staining used with the purpose to demonstrate amyloid in cadaveric material after the unsuccessfully use of all standard protocols.

Prognostic significance of the 67-kilodalton laminin receptor expression in human breast carcinomas.

BACKGROUND: The 67-kd laminin receptor is a cell-surface protein that binds laminin with high affinity. In vitro studies suggest that this protein is involved in the progression of human tumors to invasive cancers (metastasis), but there have been few in vivo studies. Identification of such proteins would allow development of therapies aimed at interfering with their mechanisms of action. PURPOSE: This large retrospective study was designed to investigate the association of expression of this laminin receptor molecule with established prognostic factors and overall survival in breast carcinoma patients. METHODS: We immunohistochemically stained archival paraffin-embedded sections of 1160 primary breast carcinomas, using an immunoperoxidase technique and the MLuC5 monoclonal antibody, which is specific for the 67-kd laminin receptor. Specimens were obtained from consecutive surgeries performed from January 1968 through December 1971. Patients with negative lymph nodes or involved regional nodes had been treated with surgery alone; those with positive axillary nodes had received surgery and radiotherapy. No chemotherapy had been administered until disease recurrence. The statistical analysis was carried out using the logrank method for the survival curves and the actuarial life table to calculate survival rates according to the different prognostic variables. RESULTS: We found statistically significant associations between laminin receptor expression and young age (P < .001), premenopausal status (P = .001), positive axillary lymph nodes (P = .01), peritumoral lymphatic invasion (P = .02), and the diameter of the tumor (P = .05). Moreover, the association of expression of the receptor protein with poor prognosis, as indicated by survival curves, was statistically significant (P < .01). For patients with receptor-negative tumors, the survival rate was 50% at 20 years; for those with receptor-positive tumors, the survival rate was 50% at 13 years. Multivariate analysis showed the laminin receptor to be an independent prognostic factor (P = .005), indicating its predictive value in relation to overall survival. CONCLUSIONS: Our data suggest that the 67-kd laminin receptor is associated with the metastatic process. IMPLICATIONS: These preliminary findings also suggest that hormones may have a regulatory role in the in vivo expression of the 67-kd laminin receptor, which supports the hypothesis that hormone therapy might inhibit expression of the receptor. Studies of expression of this receptor in tumors of patients with extremely different sex hormone levels (e.g., men and pregnant women) are in progress.

Local recurrences and distant metastases after conservative breast cancer treatments: partly independent events.

BACKGROUND: Local disease recurrences are a concern in conservative breast cancer surgery, and many studies have attempted to identify risk factors for these events. It is important to distinguish local recurrences linked to increased risk of distant spread from those due to inadequate local treatment. PURPOSE: We evaluated the incidence of local and distant recurrences according to demographic, biological, and pathologic variables in a large series of women who were conservatively and uniformly treated for breast cancer, with the aim of identifying women in whom local failure is predictive for distant metastases and who are therefore candidates for aggressive systemic treatment. METHODS: Medical records of 2233 women who had been hospitalized at the Milan Cancer Institute from 1970 to 1987 were analyzed. All women received quadrantectomy and axillary lymph node dissection followed by radiotherapy for the breast. Quadrantectomy is breast-conserving removal of most of the affected quadrant by a radial incision that includes part of the skin. The end points considered were local failures (including local recurrences and new ipsilateral carcinomas) and distant metastases. Statistical analysis employed the competing risks and multiple failures approaches. RESULTS: There were 119 local recurrences, 32 new ipsilateral carcinomas, and 414 distant metastases as first events. The timing of local failures and distant metastases differed: The yearly probability for local failures was approximately 1% up to the 10th year and for distant metastases was 5% in the 2nd year and decreased progressively until the 8th year. Young age was an important risk factor, with peritumoral lymphatic invasion also predictive for local and distant recurrences. Tumor size and axillary lymph node involvement were not related to local recurrence but were important predictors of distant metastases. Extensive intraductal component was only a risk factor for local recurrence. Early (< 2 years) local failure predicted for distant metastases compared with later failure. In local failure patients, the 5-year survival rate was 69% from failure. CONCLUSIONS: Local recurrences and distant metastases are partially independent events that occur at different times; several predicting factors also differ. However, women with local recurrences have increased risk of distant metastases. In particular, women 35 years old or younger at first diagnosis who had initial peritumoral lymphatic invasion and local recurrence within 2 years are at high risk for distant spread. For recurrence in cases with an extensive intraductal component or where initial local surgery was possibly inadequate, women are at lower risk.

Antibody response against the c-erbB-2 oncoprotein in breast carcinoma patients.

Indirect immunofluorescence analysis of sera from breast carcinoma patients whose tumors were characterized for overexpression of the c-erbB-2 oncoprotein (p185HER2) and for lympho-plasma cell infiltration, revealed no circulating antibodies specifically directed against the p185HER2 molecule in the 20 samples tested, whereas supernatants of B-cell clones, derived from Epstein-Barr virus-transformed peripheral blood lymphocytes from 10 of these patients, contained such antibodies in 6 of the 7 c-erbB-2- and lympho-plasma cell infiltration-positive cases. The antibodies contained in two of the positive supernatants immunoprecipitated a M(r) 185,000 molecule from oncoprotein-positive cell extracts that was identified as the oncoprotein in sequential immunoprecipitation experiments with anti-p185HER2 monoclonal antibodies. No cells producing antibodies with a similar reactivity were obtained from Epstein-Barr virus-transformed peripheral blood lymphocytes from breast carcinoma patients with p185HER2-negative tumors or from healthy donors. These data prove the existence of an antibody response specifically directed against the p185HER2 oncoprotein in breast carcinoma patients that may represent an important effector mechanism in the control of c-erbB-2-overexpressing tumors.

Technical note: Improvement of cadaveric skin samples (with severe morphological alteration connected to putrefaction or injury) by an extended histological processing.

INTRODUCTION: The microscopic study and the interpretation of skin samples with advanced post-mortal phenomena or with particular destructive injuries is problematic for the forensic pathologist. In an attempt of restoring the histological architecture of cadaveric skin and overcoming these types of problem, the Authors performed a histological processing that was longer than the standard: it was extended until 62 days to evaluate the improvement of the microscopic morphological aspect. MATERIALS AND METHODS: Cutaneous samples were taken from 25 cadavers (5 typologies of skin: charred, putrified, corifed, mummified and partially skeletonized), fixed with a 10%-buffered formalin and then processed in two different ways: one half of the samples was routinely addressed to the standard-time automatic technique, while the other half was manually processed with prolonged times. All the slides were then stained in Hematoxylin-Eosin. RESULTS: The standard-processed slides demonstrated marked morphological alterations and artefacts at the microscopic observation; conversely, those processed with the prolonged manual technique showed an improvement in the morphological structure, sometimes permitting the identification of the anatomical components. CONCLUSION: Though it is characterized by the inconvenience of protracted times, the application of a long-term manual histological processing to cadaveric skin samples with advanced post-mortal alteration permits to better observe the anatomical architecture of skin and it could be useful and helpful in the evaluation of such cases.

Biologic and clinicopathologic factors as indicators of specific relapse types in node-negative breast cancer.

PURPOSE AND METHODS: We evaluated, in 1,800 patients with node-negative tumors treated with locoregional therapy until relapse, the competitive risks for different types of metastasis by cell proliferation (3H-thymidine labeling index [3H-dT LI]), estrogen receptors (ERs), and progesterone receptors (PgRs), and by the integration of biologic and clinicopathologic information. RESULTS: Hormone receptor status and proliferative activity of the primary tumor were not indicative of contralateral failures. Hormone receptors failed to predict the 8-year incidence of locoregional recurrence, but they were significant indicators of distant metastasis and overall survival. The latter finding was confirmed even in multivariate analysis. Conversely, cell proliferation predicted both locoregional and distant metastases and survival, regardless of patient age, tumor size, and ER and PgR status. Recursive partitioning and amalgamation analysis ascribed to cell proliferation an important prognostic role for locoregional recurrence together with patient age and tumor size. CONCLUSION: Biologic markers, in particular cell proliferation, provide information for the different types of relapse and could complement the predictive role of pathologic staging.

Macrophage infiltrate and prognosis in c-erbB-2-overexpressing breast carcinomas.

PURPOSE: Experiments were designed to investigate the association between tumor leukocytic infiltrates with other pathologic and biologic variables in primary tumors and with prognosis, and to define the phenotype of the infiltrating leukocytes. PATIENTS AND METHODS: A retrospective series of 1,207 primary breast carcinomas was studied according to different prognostic variables, including the presence of lymphoplasmacytic infiltrate (LPI). LPI was analyzed in association with other variables and survival. Additionally, a small prospective series of surgical specimens from 75 primary breast carcinomas with infiltrating leukocytes was tested by immunohistochemistry on frozen sections to phenotypically characterize the infiltrate, using anti-CD reagents, and the tumor, using anti-c-erbB-2 oncoprotein monoclonal antibody. RESULTS: In the retrospective series, menopausal status, nodal status, tumor size, stage, grade, and p185HER2 overexpression but not LPI were found to be associated with prognosis and maintained their prognostic significance in a multivariate analysis. LPI was significantly associated with some of these independent prognostic factors, such as tumor size (P = .03), stage (P = .004), grade III carcinomas (P < .000001), and overexpression of the p185HER2 (P < .000001). In some subgroups of patients in whom LPI was found more frequently, such as grade III cases or N- and c-erbB-2-positive cases, LPI was found to be indicative of a good prognosis (P = .008 and P = .03, respectively). Phenotypic analysis of the infiltrating leukocytes revealed a preponderance of macrophages in high-grade (P = .05) or c-erbB-2-positive (P = .008) tumors, whereas T cells constituted most of the infiltrate in the other tumors. CONCLUSION: Our data demonstrate different leukocytic types in the infiltrate of breast tumors with different prognostic significance.

Immunocytochemical markers in stage I lung cancer: relevance to prognosis.

PURPOSE: This study investigated the frequency of the expression and prognostic significance of a panel of immunocytochemical markers in resected non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A total of 515 cases of pathologic stage I NSCLC were analyzed. The median follow-up time of surviving patients was 102 months. The following immunocytochemical markers were tested: blood group A and precursors of blood antigens; laminin receptor; c-erbB1/epidermal growth factor receptor (EGFR) and c-erbB2/Neu; BCl2; p53; and angiogenesis. Kaplan-Meier estimates of survival and time to recurrence were calculated for clinical variables and biologic markers using the Cox model for multivariate analysis. RESULTS: The pathologic tumor extension (pT) represented the most powerful prognostic factor for survival (P = .0008) and time to recurrence (P = .0007). None of the immunocytochemical markers emerged as an independent predictive factor for survival. Bcl2-positive tumors showed a better time to recurrence (P = .03), but the difference lost statistical significance in the multivariate analysis. Of interest, in the group of 137 patients classified as pT1N0, both EGFR expression and nonangiogenic type of vascular pattern were associated with a poorer survival (P = .02). However, data derived from subset analysis must be interpreted cautiously. CONCLUSION: Our findings do not support a relevant prognostic role of immunocytochemical markers in NSCLC. The evidence is not sufficient to alter clinical practice or even to restrict clinical trials of adjuvant treatments to predefined biologic subsets of patients.

Prognosis of breast cancer in males: an analysis of 170 cases.

A statistical analysis was performed on a series of 170 consecutive cases of operable (M0) breast cancer in males. All the patients underwent surgery. The end-points considered were: (i) overall mortality, (ii) all neoplastic events and deaths without evidence of breast disease (first event). Five- and ten-year overall mortalities were 26.9 and 54.3%, respectively. A multiple regression analysis showed that tumour size and nodal status (pT and pN) were statistically significant as prognostic factors. With regard to first events, 12 local recurrences (thoracic wall), one nodal relapse in the axilla and one contralateral tumour were observed. Primary tumours, other than breast cancer, occurred in 11 patients. The observed probability of surviving at 10 years from the treatment was definitely lower than that of the general population. For the follow-up periods of 0-5 and 6-10 years, the excess death rate per 100 man-years was 9.98 and 13.43, respectively. It appears from the analysis that prognosis of breast cancer is worse in men than in women.

Reducing colorectal cancer mortality by repeated faecal occult blood test: a nested case-control study.

Randomised trials have shown the efficacy of faecal occult blood testing (FOBT) in reducing colorectal cancer mortality, but observational studies are needed to monitor such efficacy in population programmes. We conducted a nested case-control study on a cohort of 21,879 subjects who participated in a colorectal screening programme from 1978 to 1995, undergoing at least one FOBT test. 95 fatal cases of colorectal cancer were eligible for the study. For each fatal case, 5 non-fatal matched controls were randomly selected from the cohort. FOBT screening history was less common among cases than controls. The odds ratio of colorectal cancer mortality among 'attenders' (defined as those who underwent a second FOBT within 2 years of study entry) with respect to 'non-attenders' was 0.64 (95% confidence interval 0.36-1.15). We also computed odds ratios defining exposure as one or more tests in the detectable preclinical period, hypothesising various lengths for the latter, which, however, yielded an efficacy estimate biased towards the null. A strong inverse relationship was observed between mortality and the number of tests, but this phenomenon is interpretable as 'healthy screenee bias'. The results suggest that the potential efficacy in preventing colorectal cancer mortality through annual FOBT screening may be of the order of one third.

Ten year results of a randomised trial comparing two conservative treatment strategies for small size breast cancer.

We report the 10-year results of a randomised clinical trial in which two different breast conservation treatment strategies were compared in women with small, non-metastatic primary breast cancer: quadrantectomy, axillary dissection and radiotherapy (QUART) versus tumorectomy and axillary dissection followed by external radiotherapy and a boost with 192Ir implantation (TART). No second surgery was given to women with affected surgical margins. Axillary node positive women received adjuvant medical therapy. From 1985-1987, this trial accrued 705 patients, 360 in the QUART and 345 in the TART arm. Crude cumulative incidence curves for intrabreast tumour recurrence (IBTR) and metastases as first events and mortality curves in each of the two treatment arms were computed. A crude cumulative incidence curve of IBTR as a second event (in women who had already had a local recurrence) was also computed. The two groups were compared in terms of hazard for IBTR, metastases or death occurrence by using Cox regression models, both with and without adjustment for patient age, tumour size, number of metastatic axillary nodes and histology. Possible interactions between the aforementioned prognostic factors and the type of surgery were also investigated. The two groups were well matched for baseline patient and tumour characteristics, the only exception being resection margins, which were more often positive in the TART group. At the Cox model, a significant difference between groups was detected for IBTR (P < 0.0001), but not for distant metastases and overall survival. In particular, 5- and 10-year estimates of crude cumulative incidence of IBTR were 4.7 and 7.4% in the QUART group and 11.6 and 18.6% in the TART group. The difference was not substantially affected by patient or disease characteristics. Likewise, the status of resection margins in women who underwent TART treatment did not significantly influence the risk of occurrence of IBTRs. Finally, the rate of second IBTR occurrence was relatively high, when compared with the rate of IBTR occurrence as first event. In summary, the results of this trial show that a better local control of the disease can be obtained with the more extensive surgical resection, i.e. QUART.

Use of monoclonal antibody MBr1 to detect micrometastases in bone marrow specimens of breast cancer patients.

Bone marrow specimens obtained from 121 breast cancer patients immediately after surgery were examined by an immunofluorescence method with monoclonal antibody MBr1 to detect tumour cells undetectable by other diagnostic procedures. 80 women were node-negative and 41 node-positive. In no case could conventional histology demonstrate tumour cells, whereas MBr1 was positive in 20 (16.5%) of the 121 cases. No difference was observed in MBr1 positivity between node-negative and node-positive cases (17% vs. 15%). With regard to clinical outcome (median follow-up 48 months) 27 women relapsed, including 6 of 20 MBr1-positive and 24 of 101 MBr1-negative patients. First distant metastases or death from progression of disease were taken as end-points. Multivariate analysis showed that the additional contribution of MBr1 positivity, after making allowance for other prognostic factors, was negligible.

Mucinous carcinoma of the breast. A clinicopathologic, histochemical, and immunocytochemical study with special reference to neuroendocrine differentiation.

We studied the clinical, histologic, histochemical, and immunocytochemical characteristics of 61 mucinous tumors (38 pure, 23 mixed) retrieved from a consecutive series of 1,689 infiltrating carcinomas of the female breast. The only statistically significant predictors of favorable survival were histologic (pure) type coupled with the absence of axillary lymph node metastases. Other factors, including classification into A and B types according to Capella et al., and neuroendocrine status, as assessed by the presence of argyrophilia, granins, neuron-specific enolase (NSE), and synaptophysin (SYN),-all had no influence on survival. Argyrophilic cells were found in 16 pure mucinous tumors (42%) and in the mucinous component of four mixed tumors (17%). Granin (chromogranin A or B), NSE, and SYN immunoreactivities were demonstrated in all the argyrophilic tumors. We also found NSE- and SYN-immunoreactive cells in 31 of 41 and 16 of 41 nonargyrophilic (granin-unreactive) mucinous tumors, which supports the view that mucinous carcinomas of the breast as a whole are neuroendocrine-programmed tumors.

Argyrophilic carcinoma of the male breast. A neuroendocrine tumor containing predominantly chromogranin B (secretogranin I).

Argyrophilic tumors were diagnosed in 28 of 134 (20.8%) consecutive male patients who had a carcinoma of the breast removed between 1961 and 1990. Histologically, most argyrophilic tumors showed uniform cellularity and prevalent expansive growth. Ultrastructural observation disclosed the presence of electron-dense cored granules in the cytoplasm of the tumor cells. By immunocytochemistry, 17 of 28 argyrophilic tumors (60.7%) contained chromogranin B (secretogranin I)-immunoreactive cells, whereas chromogranin A was present in four of these 17 tumors only (14.2%). Immunoblotting studies showed chromogranin B immunoreactivity similar to that found in normal neuroendocrine cells. Despite these findings, which would argue for a distinct morphologic and immunochemical entity, no statistically significant differences between argyrophilic and common male breast carcinomas were found when a number of clinicopathologic features and relapse-free survival were considered.

Argyrophilia and granin (chromogranin/secretogranin) expression in female breast carcinomas. Their relationship to survival and other disease parameters.

Ninety-one tumors (5.6%) containing argyrophilic cells were identified in a series of 1,628 consecutive primary breast carcinomas diagnosed between 1968 and 1972 at the Istituto Nazionale Tumori, Milan, Italy. Histological evaluation of these argyrophilic tumors showed the presence, either throughout the whole tumor mass (pure form) or in some areas (mixed form), of distinctive though not pathognomonic cellular features. Immunocytochemistry revealed the presence of chromogranin A or chromogranin B (secretogranin I) immunoreactivity in 86% of these argyrophilic carcinomas and of neuron-specific enolase (NSE) immunoreactivity in all of them. The three neuroendocrine markers were also immunolocalized at the ultrastructural level in the dense-core granules (granins) and the cytoplasmic matrix (NSE). Immunoblotting studies confirmed the chromogranin A and B and NSE immunoreactivities and documented the presence of secretogranin II. We also studied the relation of the histologic, histochemical, and immunocytochemical features to prognosis. There was no significant correlation between argyrophilia and such clinical parameters as age, menopausal status, tumor size, and overall survival; however, the pure form of argyrophilic tumors had a significant association with less frequent lymph node involvement and a low histologic grade.

Preliminary-results of preoperative axillary radioimmunoscintigraphy with in-111 b72.3 in breast-cancer.

Nineteen patients with clinical and mammographic diagnosis of breast cancer and 1 patient already mastectomized underwent radioimmunoscintigraphy (RIS) in order to evaluate the axillary node status before surgery. After histologic examination, ductal breast carcinomas were found in 17/19 patients and axillary metastases were found in 11 patients. RIS was performed with planar scintigraphies and SPET (Single Photon Emission Tomography) of mammary and axillary regions after intravenous injection of In-111 B72.3. Overall RIS sensitivity for breast tumors was 71% (12/17); according to the tumor site different RIS sensitivity was demonstrated (90% for lesions of external quadrants versus 43% for lesions of internal quadrants). RIS was negative in 2 patients with post-surgery diagnosis of mammary dysplasia. As regards axillary metastasis RIS sensitivity and specificity were 91% (10/11) and 78% (7/9), respectively. Human Anti-Murine Antibody (HAMA) production was shown in 16.7% (2/12) of the patients. The quantitation of In-111 B72.3 uptake (%I.D./g; mean+/-S.D.) was 0.0054+/-0.0021 in breast tumors, 0.0021+/-0.0011 in normal mammary tissue, 0.0053+/-0.0027 in axillary metastasis and 0.0032+/-0.008 in normal axillary nodes. Our data demonstrated that RIS can detect tumor spread to the axilla in patients with breast cancer. Larger pre-operative study is required to evaluate if RIS can alter the management of this disease.