Intraoperative ultrasound is an effective and preferable technique to localize non-palpable breast tumors.

INTRODUCTION: Non-palpable breast tumors represent an increasing management problem in modern Breast Units. Therefore, a simple and accurate procedure to localize these lesions is needed. To date, the most commonly used technique is wire localization, but there are some disadvantages. METHODS: We conducted a prospective study on patients with malignant or benign non-palpable breast tumors who were surgically treated and underwent intraoperative ultrasound (IOUS) from May 2006 to June 2007. Margins of excision were inked and specifically assessed by the pathologist, and were considered positive if

A standardized sentinel lymph node enhanced pathology protocol (SEPP) in patients with breast cancer.

BACKGROUND AND OBJECTIVES: Sentinel lymph node (SLN) biopsy allows enhanced pathology with serial sections and immunohistochemical analysis of the retrieved node. We present our experience with a simple, practical, pathology protocol. METHODS: We analysed 416 consecutive breast cancer patient who underwent SLN biopsy. These were studied with six couples of sections at three different levels, each stained with hematoxylin-eosin (H/E) and immunohistochemistry (IHC) (MNF 116). RESULTS: With conventional analysis the SLN was positive in 106/416 cases (25%). The addition of serial sections, according to the protocol, allowed diagnoses of micrometastases (MICRO) (n = 22) or isolated tumor cells (ITC) (n = 38) or MICRO (n = 1) in 51/416 patients (14.6%). Specifically, the diagnosis was undertaken at level I (8.9%), level II (4%), or level III (1,6%). The incidence of MICRO or ITC was not different in T1 and T2 cases (13% vs. 15%, P = 0.7). The addition of the third level of analysis added very little both in T1 and T2 cancers (1.3% vs. 3.8%, P = 0.1). CONCLUSIONS: Serial sectioning of the SLN allows diagnosis of MICRO and ITC in a significant percentage of cases. Adoption of our protocol seems practical, as the incidence of level III positivity is extremely low, particularly in T1 cancers, and additional sections would be, therefore, unlikely useful.

Survivin and Cyclooxygenase-2 are co-expressed in human and mouse colon carcinoma and in terminally differentiated colonocytes.

In the evolution of colon rectal cancer (CRC) the imbalance between cell proliferation and apoptosis is considered one of the prominent causes of tumor induction and/or progression. In order to establish the role of anti apoptotic proteins in colon cancer development, we studied with immunohistochemical techniques the expression of Survivin in a mouse model of colon carcinogenesis induced by 1,2-dimethyl-hydrazine treatment. In this mouse model Survivin was over-expressed during tumor development, showing a distribution mimicking that described in the correspondent human malignancies. We also correlated Survivin distribution with COX-2 and beta-Catenin expression patterns. The co-localization of COX-2/beta-Catenin/Survivin in the same epithelial cells in tumor samples lends credence to possible in vivo regulatory effects of COX-2 and beta-Catenin on the intracellular Survivin levels in mouse and human colon cancer.

Bone marrow and sentinel lymph node biopsy in patients with breast cancer: from staging to ultrastaging?

Bone marrow (BM) biopsy has been suggested as an independent prognostic tool to improve staging in patients with breast cancer. Two hundred and ten consecutive patients operated for breast cancer from June 2000 to June 2005 who signed an informed consent were enrolled in this protocol. Patients underwent SLN biopsy, and lymph nodes were analysed with serial sections and stained with hematossilin-eosin and immunohistochemistry. At the end of the procedure a BM aspirate from the iliac crest was obtained and 5-10 cc of blood collected. A CEA specific nested reverse transcriptase (RT) polymerase chain reaction (PCR) assay was used to examine BM samples. Results were blinded to both patients and clinicians. The median age of the patients was 56 years (range 34-80), and the median tumor diameter 1,5 cm (range 0.2-4.5). BM aspirates were unsuccessful in ten patients, and RT-PCR was not technically feasible in seventeen women, leaving 183 patients available for analysis of results and follow up. SLN biopsy allowed diagnoses of occult metastases (micrometastases and isolated tumor cells) in 16% of patients (29/183). 25% of T1N0 patients (23/92), 35% of T2N0 patients (6/17), and 44% of N1-2 patients (32/72) were BM+ (p = 0.03). At a median follow up of 35 months 5/122 in the BM- group and 6/61 in the BM+ group have relapsed (p = 0.2), while 1/122 and 4/61 have died of disease (p = 0.04) In conclusion, ultrastaging of breast cancer patients may identify a substantial subgroup of patients N-/BM- who may not require adjuvant chemotherapy, as well as a subgroup N-/BM+ with a decreased survival who may need more aggressive therapies. Further follow-up is needed to confirm this hypothesis, and several studies are under way.

[Hormone-dependence and C-ERBB2: relationship between estrogen receptor expression, estrogen-regulated proteins, and C-ERBB2 in breast carcinoma]. / Ormono-dipendenza e C-ERBB2: rapporto tra espressione dei recettori estrogenici, estrogen regulated proteins e C-ERBB2 nel carcinoma della mammella.

We reviewed 1491 consecutive cases of operated breast cancer between 1999-2004, and found that hormone-dependence, particularly if evaluated with functional markers of the estrogen receptor (estrogen regulated proteins, ERP), is inversely proportional to antigen neu expression. Our data confirms that ERP can give additional information on the probability of response to hormonal therapy.

[Towards the standardization of sentinel lymph node analysis in women with breast cancer]. / Verso una standardizzazione dell'analisi del linfonodo sentinella in donne con cancro della mammella.

Sentinel lymph node biopsy allows enhanced pathology through serial sections and immunohistochemical analysis of the retrieved node, with detection of micrometastases and isolated tumor cells not otherwise recognized. We present our experience with a simple, effective, pathology protocol requiring six couples of sections at three different sentinel lymph node levels. Additional micrometastases or ITC were diagnosed in 51/416 patients (14.6%).

[Does incidence of sentinel lymph node metastasis increase after diagnostic manipulation in women with breast cancer?]. / Aumenta l'incidenza di metastasi nel linfonodo sentinella dopo manipolazione diagnostica in donne con cancro della mammella?

503 patients were retrospectively evaluated to assess whether a previous needle or core biopsy, or surgical surgical excision of the primary tumor are associated with passive dislodgment of tumor cells in the sentinel lymph node, as reported in recent publications. We could not identify any increased incidence of sentinel lymph node micrometastases or isolated tumor cells after diagnostic manipulation of the primary tumor.

[Predictive variables of lymphatic metastasis in breast carcinoma with a diameter below 2 cm]. / Variabili predittive di metastasi linfonodali nei carcinomi mammari di diametro inferiore a cm 2.

The axillary lymph node status of patients with newly diagnosed breast cancer remains the most important prognostic information available at the moment. However, only a minority of patients presents with such node metastases at diagnoses. We reviewed our database and studied 500 consecutive patients with early breast cancer, and found that age inferior to 50 years, high grade, diameter superior to 1 cm, elevated Ki-67, and expression of oncogene p-53 are all factors associated with lymph node metastases.

Is apoptosis a diagnostic marker of acute myocardial infarction?

OBJECTIVE: To investigate and quantify the presence of apoptosis in early myocardial ischemia in humans. METHODS: Histologic sections from the left and right ventricles of 16 hearts with impending myocardial infarction were stained with terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick end labeling (TUNEL) method and with antibodies to p53, bcl-2, cpp32, FAS, FAS-L, and bax. DNA electrophoretic analysis was also performed. RESULTS: According to the inclusion criteria, all 16 cases showed morphologic changes consistent with ischemia and/or reperfusion. TUNEL results were positive in 14 of the 16 ischemic areas. Unexpectedly, they were also positive in "remote from ischemia" myocardium of both the left and right ventricles. DNA electrophoretic analysis confirmed the results of TUNEL. Immunohistochemistry was uniformly negative, probably because of autolysis phenomena. CONCLUSIONS: We showed that apoptosis precedes necrosis in humans, but the detection of apoptosis cannot be used as a diagnostic tool, since it can also be triggered by nonischemic events.

[Differential diagnosis in a case of brown tumor caused by primary hyperparathyroidism]. / Diagnosi differenziale in un caso di tumore bruno da iperparatiroidismo primitivo.

Fibrous-cystic osteitis is a bone metabolic disorder related to hyperparathyroidism. This pathological condition shows a bone catabolism enhancement, due to increased level of PTH. Brown tumour is a uni- or multi-focal bone lesion, which represents the terminal stage of the hyperparathyroidism-dependent bone pathology. This focal lesion is not a real neoplasm showing itself as a cellular reparative process, mainly interesting the jaws, specially the mandible. Because of the similar radiological features (cyst-like radiolucency) showed by other lesions, the diagnosis can be difficult. Histology cannot guarantee a certain diagnosis, some lesions, such as giant cell tumour, giant cell granuloma, aneurysmal bone cyst and cherubism, show a similar macroscopical and microscopical features. Differential diagnosis is possible only by comparative evaluation of clinical, radiological and biochemical evidences. Personal experience with a patient affected by maxillary expansive lesion previously diagnosed as GCT is reported. Radiological examinations showed another cyst-like lesion involving the mandible. Clinical history and multifocality of lesions were suggestive for the presence of a systemic disease, laboratory data allowed a primary hyperparathyroidism diagnosis. Parathyroid scintigraphy was performed and detected a parathyroid adenoma. In first instance the patient underwent to surgical operation on the jaws in order to stop the rapid progression of bone lesions, and then another operation for the removal of parathyroid adenoma was performed.

Solitary crystal-storing histiocytosis of the tongue in a patient with rheumatoid arthritis and polyclonal hypergammaglobulinemia.

A 73-year-old woman with a long history of rheumatoid arthritis and polyclonal hypergammaglobulinemia developed a solitary mass in the tongue, which on morphologic and immunohistochemical analyses was consistent with crystal-storing histiocytosis, a rare condition commonly described in association with clonal lymphoplasmacytic disorders. The lesion consisted of a localized collection of histiocytes filled with numerous eosinophilic crystals immunoreactive for both kappa and lambda light chain and gamma heavy chain antibodies. Mature lymphocytes and plasma cells were present both throughout and around the lesion. Since a clonal lymphoplasmacytic neoplasm was ruled out by clinical and immunohistochemical studies, we consider that, in this case, crystal-storing histiocytosis was consequent to polyclonal hypergammaglobulinemia and suggest that this rare histiocytosis is not specific to lymphoplasmacytic neoplasms, but may represent a reaction to high values of normal (or abnormal) immunoglobulins.