Carmela Giardina

Prognostic factors in breast cancer: the predictive value of the Nottingham Prognostic Index in patients with a long-term follow-up that were treated in a single institution

The Nottingham Prognostic Index (NPI) is an index, derived from a retrospective multivariate study, that is able to predict survival in patients with breast cancer. The index is based on tumour size, lymph node stage and histological grade and allows the stratification of patients into three different prognostic groups. The aim of this study was to verify, according to our experience with a long-term follow-up, the effect of some prognostic variables on survival and to establish the independent influence of each of them by means of a survival regression analysis. Then we applied the NPI to the same group of patients in order to assess the predictive power and reproducibility of the index. 402 patients treated from January 1979 to December 1987 were evaluated. In multivariate analysis (Cox proportional hazard model), only size, lymph node involvement and histological grade remained independent prognostic factors. The survival curves obtained after applying the NPI are similar to those for the factors with independent prognostic significance derived from our multivariate analysis. Our improved survival rates may be attributed to the administration of adjuvant therapies to a larger number of patients. The NPI allow us to accurately predict prognosis and we advocate its more common use.

Malignant deciduoid mesothelioma of the pleura: report of two cases with long survival.

Malignant deciduoid mesothelioma of the pleura: report of two cases with long survival

Osteoblastoma of the mandible: Clinicopathologic study of four cases and literature review

Osteoblastoma is a benign bone tumor accounting for 1% of all bone tumors; it commonly involves the spine and the sacrum of young individuals, with less than 5% being localized to the posterior mandible. In view of its rarity in the maxilla and mandible, osteoblastoma is rarely diagnosed as such in the absence of interdisciplinary cooperation.

A Further Validation of Subareolar Injection Technique for Breast Sentinel Lymph Node Biopsy

BackgroundIn this study we performed subdermal injection of 99mTc-labeled albumin combined with subareolar (SA) injection of blue dye, and we compared this technique with two techniques previously used in terms of the success of sentinel lymph node (SLN) identification, false-negative (FN) rate, and the overall accuracy and sensitivity of the three procedures. In all patients we performed a complete axillary lymph node dissection.MethodsFrom January 1999 to September 2004, a total of 195 patients with localized breast cancer were treated. Patients were subdivided into three groups. In patients in group 1 (n = 115; January 1999 to December 2001), lymphoscintigraphy together with injection of vital dye was performed; in group 2 (n = 40; January to October 2002), SA injection of blue dye alone was performed; and in group 3 (n = 40; November 2002 to September 2004), SA injection of blue dye and subdermal injection of radioisotope was performed.ResultsThe success rate of identifying an SLN by a combination of the two techniques was 95% in group 1 and 100% in group 3. The FN rate was 9% in group 1 and 0% in groups 2 and 3. The overall accuracy of lymphatic mapping was 97% in group 1 and 100% in groups 2 and 3. Sensitivity was 91% in group 1 and 100% in groups 2 and 3.ConclusionsThis study of SA injection for SLN biopsy using dual tracers demonstrates a high SLN identification rate and an absent FN rate. We propose that injection into the SA plexus is the optimal way to perform lymphatic mapping of the breast. This technique seems to be feasible even in patients with multicentric cancers.

Oral squamous cell carcinoma during long-term treatment with hydroxyurea.

Hydroxyurea (HU) is commonly used for the treatment of chronic myelogenous leukaemia, polycythemia vera and essential thrombocythaemia. Patients receiving HU present a number of side‐effects including skin/mucosa changes and tumours. Mucocutaneous abnormalities include xerosis, ichthyosiform lesions, dark brown pigmentation of skin folds and nails, malleolar ulcers, oral mucositis and oral ulcers. Cutaneous squamous/basal cell carcinomas have also often been reported following long‐term administration of HU. HU‐induced carcinogenesis is due to both the mutagenic potential of this agent and to an impairment of DNA repair mechanisms after damage by external factors such as ultraviolet radiation. Oral cancer following long‐term treatment with HU has been reported only once, in a patient with concomitant multiple skin tumours. We present the unique case of a patient with polycythemia vera who developed oral cancer after 15 years of HU therapy.

Sentinel lymph node micrometastasis and risk of non-sentinel lymph node metastasis: validation of two breast cancer nomograms.

INTRODUCTION The aim of this study is to validate the predictive value of the Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram and the Tenon score system in our sentinel lymph node (SLN)-positive series, and to define their actual usefulness when applied to the subgroup of patients with micrometastasis in SLN. PATIENTS AND METHODS The study population consisted of 95 patients: 68 with macrometastasis and 27 with micrometastasis in the SLN. The predicted probability of non-SLN metastasis was calculated for each patient by using a computerized model from the MSKCC Web site. Furthermore, we have applied the Tenon score to our dataset. The receiver operating characteristic (ROC) curves were drawn and the areas under the curve (AUCs) were calculated to assess the discriminative power of the nomograms. The ROCs and relative AUCs were calculated both for all the patients in the study and for 2 subgroups. RESULTS The AUC for the entire study population was 0.720 in MSKCC nomogram: and 0.754 in Tenon nomogram. In 68 patients with macrometastasis in SLN, the AUC was 0.760 in MSKCC nomogram and 0.707 in Tenon score. Micrometastasis in SLN were found in 27 patients: AUC was 0.595 in MSKCC nomogram and 0.734 in Tenon score. CONCLUSION In our results the MSKCC nomogram did not provide a reliable predictive model for identifying patients with low risk of non-SLN metastasis in the event of micrometastasis in SLN. Our validation study shows that the Tenon score is more accurate and useful in patients with micrometastasis in SLN.

Tamoxifen binding sites heterogeneity in breast cancer: a comparative study with steroid hormone receptors

Steroid receptors and tamoxifen binding sites (TBS) were assayed in the soluble fraction of 121 primary breast cancers. Scatchard analysis of TBS in high speed supernatant (100,000 g) showed one population of binding sites; however, biphasic plots were obtained in low speed supernatants (40,000 g). Isoelectric focussing of supernatants preincubated with radioactive tamoxifen identified two classes of TBS (pI 4.1-4.6) which have different binding affinities and bind neither oestradiol nor diethylstilbestrol. Association between TBS and steroid receptors was: TBS positive/progesterone receptor positive 32.6%, TBS positive/glucocorticoid receptor positive 52.7%, TBS positive/oestrogen receptor positive 60% and TBS positive/androgen receptor positive 72.2%. We conclude that heterogeneous TBS are present in low speed fractions and can be easily separated from the oestrogen receptor by isoelectric focussing. The association between TBS and steroid receptor status could be of clinical value in the management of primary breast cancer.

Morphological parameters of lobular in situ neoplasia in stereotactic 11-gauge vacuum-assisted needle core biopsy do not predict the presence of malignancy on subsequent surgical excision

The management of lobular in situ neoplasia (LN) when diagnosed on core biopsy remains a controversial issue. The present study aimed to investigate the association between morphological parameters of LN on vacuum‐assisted needle core biopsy (VANCB) and the presence of malignancy (ductal carcinoma in situ, pleomorphic lobular carcinoma in situ, or invasive carcinoma) at surgical excision (SE).

Effect of the use of vital dye, lymphoscintigraphy, or a combination for axillary lymphatic mapping and sentinel node biopsy in breast cancer

Axillary dissection in patients with breast cancer is associated with significant morbidity. Because 85% of the patients with a cancer ≤1 cm have negative axillary nodal status, axillary dissection in these patients is only a staging procedure. A study of the sentinel lymph node (SLN) biopsy has been developed to determine axillary nodal status by means of a minimally invasive procedure. The aim of our study was to estimate the degree of reliability for identifying the SLN using a vital dye or lymphoscintigraphy, or a combination of the two. From January 1999 to May 2000 a series of 60 patients with breast cancer were evaluated for enrollment in the study. For the mapping procedure, lymphoscintigraphy in combination with injection of vital blue dye was performed in 24 patients, and vital dye alone was utilized in 36. Complete axillary dissection was performed in all patients after SLN biopsy. The mapping procedure was possible in 59 cases (98.3%). The SLNs were positive in 19 patients (32.2%) and negative in 40; in 38 of the 40 patients all axillary nodes were negative. There was concordance in 57 of 59 cases (96.6%). The false-negative rate was 5% (2/40). The overall sensitivity of the SLN biopsy was 90.4% (19/21), with a negative predictive value of 95% (38/40). Our results indicate that SLN biopsy guided by a gamma probe in combination with vital dye can identify a negative axilla with high accuracy. We conclude that the use of both techniques produces an optimal result, as they are complementanry.RésuméLa lymphadénectomie de l’aisselle pour cancer du sein est responsable d’une certaine morbidité. Puisque 85% des patients ayant un cancer <1 cm n’ont pas d’atteinte ganglionnaire axillaire, la lymphadénectomie chez ces patients ne sert qu’au staging. L’étude des ganglions satellites, basée sur la biopsie de ganglion sentinelle (GS), a été développée pour pouvoir déterminer l’état ganglionnaire axillaire par un procédé minimal-invasif. Le but de notre étude a été, pour optimiser les résultats, d’évaluer la fiabilité de l’identification du GS par l’utilisatiaon des colorations vitales ou la lymphoscintigraphie ou les deux. Entre janvier 1999 et mai 2000, 60 patientes porteuses de cancer du sein ont été incluses dans l’étude. La coloration vitale a été utilisée seule (n=36) ou en combinaison avec la lymphoscintigraphie (n=24). Chez toutes les patientes, une lymphadénectomie axillaire complète a été réalisée après biopsie du GS. Une cartographie a été obetnue avec succès dans 59 cas (98.3%). Les GS étaient positifs chez 19 patientes (32.2%), négatifs chez 40 patientes alors que chez 38 de ces patientes, tous les ganglions axillaires étaient indemnes. Il y a eu concordance donc dans 57/59 cas (96.6%). Le taux de faux négatifs a été de 5% (2/40). La sensibilité globale de la biopsie du GS a été de 90.4% (19/21), avec une valeur prédictive négative de 95% (38/40). Nos résultats indiquent que la biopsie du GS guidée par une sonde γ en combinaison avec une coloration vitale pourrait identifier avec une grande précision une aisselle négative et nous conclusons que l’utilisation des deux techniques produit un résultat optimal en raison de leur complémentarité.ResumenEl vaciamiento axilar en el cáncer de mama origina una importante morbilidad. Dado que el 85% de los pacientes cuyo cáncer de mama tiene un tama no igual o menor a 1 cm, presentan adenopatías axilares negativas, la disección de la axila sólo tiene por objeto verificar la estadificación del proceso neoplásico. El concepto de biopsia del ganglio centinela se ha desarrollado con objeto de averiguar la estadificación ganglionar, mediante una intervención mínimamente invasiva. El presente trabajo tiene por objeto averiguar el grado de fiabilidad, en la identificación del ganglio centinela (SLN), de los colorantes vitales, de la linfoescintigrafía, o, para optimizar los resultados, de la combinación de ambas técnicas. Desde enero de 1999 a mayo de 2000, se estudiaron con estos fines 60 pacientes con cáncer de mama. La cartografía en 24 enfermos se realizó mediante linfoescintigrafía combinada con la inyección de contraste vital azul; en 36 sólo se emploó la coloración vital. En todos los pacientes, tras la biopsia del ganglio centinela (SLN), se realizó un vaciamiento total de axila. La cartografía fue posible en 59 casos (98.3%). El SLN fue positivo en 19 (32.2%) de los pacientes; negativo en 40, de los que en 38, registramos adenopatías axilares negativas. Así pues, observamos una concordancia en 57/59 casos (96.6%). El porcentaje de falsos negativos fue del 5% (2/40). La sensibilidad global de la biopsia del SLN fue del 90.4% (19/21) con un valor pronóstico negativo del 95% (38/40). Nuestros resultados demuestran que la biopsia del SLN guidad por gammagrafía combinada con la utilización de colorantes vitales permite descartar la presencia de metástasis ganglionares axilaraes, alcanzándose resultados óptimos si se emplean conjuntamente ambas técnicas.

Sentinel lymph node biopsy in patients with pure and high-risk ductal carcinoma in situ of the breast.

Aims and Background The role of sentinel lymph node biopsy in patients initially diagnosed with ductal carcinoma in situ resides in determining the predictors of invasive disease. The aim of the present study was to examine the incidence of sentinel lymph node metastases in a selected group of patients, with characteristics of high-risk ductal carcinoma in situ, in order to determine the clinical usefulness of sentinel lymph node biopsy. Methods A total of 90 patients with a biopsy diagnosis of ductal carcinoma in situ were treated. Fifty-two patients with high-risk ductal carcinoma in situ had sentinel lymph node biopsy. The following characteristics of the primary tumor were considered as indicative of a risk of invasive disease: presence of palpable mass, mammographic mass, multicentric disease that required mastectomy, and histologically high nuclear grade or non-high nuclear grade with necrosis. Subdermal injections of 99mTc-labeled human albumin and subareolar injection ofblue dye were used for sentinel lymph node identification. All sentinel nodes were sectioned serially and stained with hematoxylin and eosin. Immunohistochemical analysis was performed using a cytokeratin monoclonal antibody. Results A positive sentinel lymph node was found in only one patient (1.9%). The patient had a double lesion, and core-needle biopsy showed an atypical ductal hyperplasia and a intermediate degree of ductal carcinoma in situ. At pathologic review of the specimen, no invasive aspect was detected. Conclusions The results of our study indicate that sentinel lymph node metastasis in pure ductal carcinoma in situ is extremely uncommon. We therefore suggest that sentinel lymph node biopsy might be indicated for patients with ductal carcinoma in situ detected as a palpable mass or as large extensive microcalcifications, as well as for patients who are undergoing mastectomy, especially with immediate reconstruction.