Use of fine needle aspiration for solid breast lesions is accurate and cost-effective

BACKGROUND: Palpable breast tumors have traditionally been diagnosed with open biopsy or core biopsy. We propose fine needle aspiration biopsy (FNA) as a reliable, cost-saving initial procedure in these patients. METHODS: Eighty-five palpable solid breast masses of the breast in 85 patients were classified by a combination of physical examination, mammography, and/or ultrasound as probably benign, indeterminate, or highly suspicious for cancer. All tumors had FNA biopsies. All patients had either a confirmatory open biopsy (55) or close clinical follow-up (30) with a mean follow-up of 29 months (range 6 to 36). RESULTS: Thirty-four patients classified as clinically benign had a benign FNA biopsy. No cancers were detected in this group by either open surgical biopsy or clinical follow-up. Twenty patients were classified clinically as indeterminate. All had FNA biopsies, and 6 were either positive for cancer or suspicious for cancer. Fourteen patients had negative FNA biopsies. Five of the 6 abnormal biopsies had cancer on open biopsies. The 1 false-positive result occurred in a lactating patient. Thirty-one patients were classified clinically as highly suspicious for cancer. Twenty-three were confirmed as cancer with FNA biopsy. Eight needed open surgical biopsy to confirm cancer. All 31 patients clinically suspicious for cancer had cancer. In patients classified clinically as highly suspicious or probably benign, FNA was a reliable first diagnostic step (100% positive predictive value, 100% specificity, 87% sensitivity, and 89% negative predictive value). CONCLUSIONS: Fine needle aspiration biopsy of solid palpable breast lesions should be the diagnostic procedure of choice for those patients classified clinically as probably benign or clinically as highly suspicious for cancer. Cost analysis revealed elimination of an open biopsy in such cases would save $1,100 per patient. For highly suspicious cases, a negative fine needle aspiration should not deter an open surgical biopsy. For patients classified as indeterminate, fine needle aspiration biopsy results are not reliable enough to determine treatment.     

A pivotal role for glutamate in the pathogenesis of schizophrenia, and its cognitive dysfunction

PURPOSE: To compare the outcome for patients with squamous cell carcinoma of cervical lymph nodes metastatic from an unknown primary site who were irradiated to both sides of the neck and potential mucosal sites with opposed photon beams, and for those irradiated to the ipsilateral side of the neck alone with an electron beam. METHODS AND MATERIALS: Fifty-two patients with squamous cell carcinoma metastatic to cervical lymph nodes from an unknown primary site were irradiated by two different methods. Thirty-six were irradiated with a bilateral technique (BT), i.e., to both sides of the neck, including the naso-oro-hypopharyngeal mucosa, and 16 were irradiated with an electron beam (EB) to the ipsilateral side of the neck alone. Twenty patients of the BT group and 11 of the EB group had cervical lymph node dissections, and the remaining 21 patients had lymph node biopsies, prior to radiotherapy. RESULTS: Tumor control in the ipsilateral side of the neck did not differ for either radiation technique, but was significantly higher after lymph node dissection than after biopsy (90 vs. 48%; p = 0.0004). Control of subclinical metastases in the contralateral cervical lymph nodes was higher for patients irradiated with BT than for patients irradiated with EB (86 vs. 56%; p = 0.03). The occult primary was later discovered in 8% of the patients in the BT group and 44% of the EB group (p = 0.0005). The disease-free survival rate at 5 years for patients who had lymph node dissection prior to irradiation was 61%, and was 37% for those who had biopsy (p = 0.05). Only 20% of patients who subsequently developed an occult primary were salvaged and survived for 5 years after salvage treatment. CONCLUSION: Bilateral neck and mucosal irradiation is superior to ipsilateral neck irradiation in preventing contralateral cervical lymph node metastases and the subsequent appearance of an occult primary cancer. Both techniques combined with cervical lymph node dissection were equally effective in controlling the ipsilateral neck disease.     

Reliability of needle biopsy of solitary thyroid nodules in view of surgical indications

To evaluate the accuracy of fine-needle biopsy in the management of the solitary thyroid nodules, 320 biopsies without aspiration were performed in 212 patients, iteratively in 91 cases. Among the 212 initial biopsies, 93 smears were found presumably benign (43.9%), 6 malignant (2.8%), 49 benign implying cytologic control (23.1%), 24 suspicious with decision to operate (11.3%), 40 inadequate (18.9%). On 67 surgical indications (malignant or suspicious cytology, or clinical data), 59 operations were performed. The 11 diagnosed cancers (5.2% of the patients; 18.6% of the operations) correspond to six malignant and five suspicious cytologies at the first or second biopsy. On 145 cases without decision to operate, 125 were clinically surveyed, with sometimes another biopsy (mean survey: 27.6 months; range: 6-80 months), and it was never necessary to modify the initial expectancy attitude. Our results, rather similar to those related by most of the previous publications, confirm that the fine-needle biopsy is a reliable and effective means for the etiologic diagnosis of thyroid nodules and the indications for operative intervention. It spares many patients from a useless operation and is worthy to take a leading place in exploring these nodules.     

Prediction of occult neck metastases in laryngeal carcinoma: role of proliferating cell nuclear antigen, MIB-1, and E-cadherin immunohistochemical determination

The aim of this study is to investigate the predictive value of proliferative activity assessment and E-cadherin expression by means of immunohistochemistry in identifying patients with laryngeal squamous cell carcinoma at a high risk for occult node metastasis. Thirty consecutive patients treated for laryngeal carcinoma with false clinically negative nodes (occult metastases, pN+) between the years 1980 and 1990 were selected for this study. A group of 30 cases with negative cervical lymph nodes (pN-) having a similar anatomic site and tumor size distribution was used as control. In each case, several histological parameters, including grade, pattern of invasion, number of mitosis (x10 high-power field), tumor inflammatory infiltrate, and tumor sclerosis, were assessed. Proliferative activity was determined using immunohistochemical staining for proliferating cell nuclear antigen (PCNA) and MIB-1. Other putative prognostic factors investigated at the immunohistochemical level were the cell adhesion molecule E-cadherin and two oncoproteins, p53 and c-erbB-2. In pN+ cases, the expression of PCNA and MIB-1 was significantly higher than in the pN- group. Moreover, a significant loss of E-cadherin expression was observed in carcinomas with occult metastases. No differences in p53 and c-erbB-2 oncoproteins were found between pN+ and pN- cases. Among the other pathological parameters examined, only histological grade was significantly associated with the presence of occult metastases, but on multivariate analysis, this relationship was lost. We conclude that PCNA, MIB-1, and E-cadherin are independent predictors of occult nodal disease in laryngeal squamous cell carcinoma, and their immunohistochemical determination could be useful in identifying patients with clinically negative lymph nodes who are at considerable risk for occult metastases and who may benefit from elective neck dissection.     

Comparison of digital rectal examination and biopsy results with the radical prostatectomy specimen

PURPOSE: Digital rectal examination is integral to staging prostate cancer. Ultrasound guided biopsy establishes the diagnosis, and it may provide useful information regarding disease grade and extent. Treatment decisions are largely based on information gained from digital rectal examination and biopsy but this information is only useful if it correlates with the radical prostatectomy specimen and prognosis. We correlated digital rectal examination and transrectal ultrasound guided biopsy results with a detailed analysis of the radical prostatectomy specimen. MATERIALS AND METHODS: The accuracy of an abnormal digital rectal examination for predicting the location and extent of cancer was assessed in 89 patients thought to have clinical stage T2 disease. We evaluated 155 patients with clinical stages T1c and T2 disease to correlate the location of positive biopsies with the tumor site in the prostate. Radical prostatectomy specimens were completely sectioned at 2 mm. intervals, and tumor extent and location were recorded. RESULTS: In 85 patients a unilateral lesion was suspicious on digital rectal examination, that is stage cT2. The final pathological review revealed cancer on the suspicious side in 82 cases (96%) with tumor confined to the same lobe in only 23 (27%), bilateral disease in 59 (69%) and tumor confined to the contralateral lobe in 3 (4%). In 4 patients with a palpable bilateral abnormality a bilateral lesion was confirmed on final pathological evaluation. Digital rectal examination demonstrated a 36 and 31% incidence of extracapsular tumor extension and positive surgical margins, respectively, on the clinically benign side. In 100 patients only unilateral biopsy was positive. The final pathological evaluation revealed cancer in the biopsy positive side in 95 cases (95%) with tumor confined to the ipsilateral lobe in only 26 (26%), bilateral disease in 69 (69%) and tumor confined to the contralateral lobe in 5 (5%). In 46 of the 55 patients (84%) with bilateral positive biopsies tumor involved both sides but the pathologist did not identify cancer in both lobes in 9 (16%). While 100 patients had a unilateral negative biopsy, analysis of the prostatectomy specimen revealed carcinoma in the benign lobe in 74 (74%). Moreover, extracapsular tumor extension and a positive surgical margin were observed on the biopsy negative side in 31% of the patients. The degree to which digital rectal examination and biopsy results confirmed the final pathological evaluation was assessed using the kappa statistic, which revealed only slight agreement with each factor. The correlation of digital rectal examination and biopsy results with the location of extracapsular extension and positive margins was evaluated by the Spearman coefficient of correlation, which indicated poor agreement. When patients with unilateral versus bilateral positive biopsy were compared with respect to prognostic parameters, the difference was statistically significant for initial serum prostate specific antigen, the percentage of surface involved by tumor, biopsy and final Gleason scores, and the incidence of extracapsular extension of tumor. CONCLUSIONS: Digital rectal examination and the interpretation of prostate biopsy are not accurate clinical tools for defining the location and extent of prostatic carcinoma. Bilateral positive biopsy may be useful as an adjunct to the current clinical staging system.     

The optimal diagnosis of recurrence and metastases in female genital cancer by needle biopsy (author's transl)

The "true-cut" disposable biopsy needle was used for 95 needle biopsies in 42 patients who were suspected to have a recurrence or metastases of low lying gynaecological cancer. Up to 3 biopsies per patient were obtained. In 21 patients the clinical suspicion of malignant was verified by microscopic examination. The needle biopsies were done as often by the vaginal as by the rectal route. Because of the low incidence of complications the needle biopsy was recommended for the definite diagnosis and follow-up examination of suspicious low lying gynaecological tumors.     

Microthoracoscopy: at the cutting edge of thoracic surgery

60 patients, 64 years old on average, with no evidences of prostatic cancer, but with a PSA level greater than 8.9 ng/ml, have undergone six transrectal systematic sextant biopsies. All patients had no suspicious finding on digital rectal examination. Ultrasound transrectal examinations did not show hypoechoic areas suspected of a prostatic cancer. We used an automatic biopsy gun fitted with an 18 gauge biopsy needle. Three biopsies in each lobe, at the apex, in the midline zone and at the base of the prostate, in the parasaggital plane, was performed. No complications were found during following days. Of the 60 men, with a non suspicious prostate on rectal examination, 12 had prostatic cancer. They had, on average, a PSA level of 10.8 ng/ml. The PSAD level was, on average, of 0.18 and the Gleason score was, on average, of 3.8. The patients who underwent pelvic lymphadenectomy and radical prostatectomy did not have an infiltration of the glans capsule of seminal vesicles and no lymph node metastasis were found. In our study, the digital rectal and ultrasound examination alone would have missed the 23% of prostatic cancers. Therefore, according to the literature, the PSA makes us able to discover prostatic cancer more than the clinical and instrumental evaluation alone. Furthermore the ultrasound examination presents some diagnostic limits. Particularly it is very difficult to detect small cancer arising into the hypoechoic multinodular adenoma of the transition zone. In addition 10-20% of cancers, arising into the peripheral zone, are hysoechoic with the surrounding parenchyma. For that reason, when PSA value is greater then 8.9 ng/ml without clinical or ultrasound evidence of cancer, we recommend to perform six systematic sextant biopsies. At present, the real question is to determine whether this early diagnosis is useful for patients, because there is no certainty of the therapeutic benefit in terms of quantity and quality life.     

Therapeutic application of cytokines and future prospect of the drug design]

The biopsy of different tissues were reviewed in 34 patients with intrathoracic sarcoidosis for determining their value on the diagnosis of sarcoidosis. Biopsy of different tissues was performed by routine method. The transbronchial lung biopsy (TBLB) was done under bronchoscope. The diagnosis was confirmed in 90.9% (10/11) of the biopsies of periphery lymph nodes, 75.0% (3/4) of the scalene nodes' biopsies, 68.4% (13/19) of the transbronchial lung biopsies and 70.6% (12/17) of the bronchial mucosal biopsies (BMB) through fibroptic bronchoscopy. Only 4 in 7 patients were diagnosed through skin biopsies. Kveim test was positive in 5 of 6 patients. Both TBLB and BMB were undertaken in 16 patients. The coincidence ratio between them was as high as 81.3%. The total diagnostic percentage through bronchoscopy was 87.5%. Significant differences were found between the results of TBLB or SMB before and after 1990 (P < 0.05 and 0.01 separately proved by chi 2 test). After 1990, 85.7% of TBLBs and 92.3% of BMBs were diagnostic. According to the study, TBLB and BMB were the methods that were repeatable, highly diagnostic, less invasive, and mutually compensable. They were superior over the other methods in the diagnosis of sarcoidosis. The diagnostic yield could be elevated by the accumulation of experiences and the improvement of techniques. They deserved recommending in the clinical practice.     

Efficacy of transbronchial biopsy in pulmonary vaculitides

This study was performed to determine the value of transbronchial biopsy (TBB) in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides and mild-to-moderate pulmonary involvement. Included in the study were 19 patients with Wegener's granulomatosis (WG) and six patients with Churg-Strauss syndrome (CSS) with evidence of active pulmonary disease but without gross parenchymal lesions accessible by radiologically guided biopsy. All of the patients had undergone staging examinations which included TBB taken from peripheral lung tissue and from any focal tracheobronchial lesions. Any suspicious lesion in the upper respiratory tract was biopsied by an otolaryngologist and the number of positive biopsies was compared with that of TBB. In the WG patients, only two out of 17 biopsies of alveolar tissue yielded histopathological findings supporting the diagnosis of WG. In five WG patients, ulcerative or exophytic airway lesions were found whose histopathologies were invariably positive. Otolaryngological examination revealed abnormal findings in 19 WG patients and biopsies from these sites yielded positive results in 13 instances. In CSS, TBB produced a diagnostically helpful histopathology in four of six cases and biopsies from the upper respiratory tract were positive in five out of six cases. We conclude that transbronchial biopsies of alveolar tissue are seldom positive in Wegener's granulomatosis patients with mild-to-moderate pulmonary disease unless they are taken from grossly abnormal lung areas. Conversely, ulcerative, exophytic or stenotic tracheobronchial lesions had a high rate of positive findings. These results further suggest that the upper rather than the lower respiratory tract should be the biopsy site of first choice in Wegener's granulomatosis. In Churg-Strauss syndrome, the upper and lower respiratory tract seem to yield a roughly equal number of positive biopsies.     

Predicting regional lymph node metastasis in carcinoma of the penis: a comparison between fine-needle aspiration cytology, sentinel lymph node biopsy and medial inguinal lymph node biopsy

OBJECTIVE: To evaluate the accuracy of clinical examination and fine-needle aspiration cytology (FNAC) in detecting groin metastases in patients with carcinoma of the penis, and to assess the positive and negative predictive value (PPV, NPV) of a preliminary sentinel lymph-node biopsy (SNB) and biopsy of the most medial of the horizontal group of inguinal lymph nodes (MIN) in selecting patients for an ilio-inguinal block dissection. PATIENTS AND METHODS: The study comprised 28 patients (56 groins) with Stage I (one), Stage II (11) and Stage III (16) carcinoma of the penis. All patients underwent a detailed clinical examination followed by FNAC of the palpable inguinal nodes, and were subsequently submitted for block dissection. The MIN, the SN and the rest of the inguinal and iliac nodes were histologically examined separately for metastases. RESULTS: The clinical evaluation had a sensitivity of 74%, a specificity of 61%, a PPV of 57% and a NPV of 77%. The corresponding values for FNAC were all 100%, and the specificity and PPV for both MIN and SN were 100%. The sensitivity and NPV of MIN were higher than for SN, although not significantly so. CONCLUSION: Clinical examination alone is inaccurate in selecting patients with carcinoma of the penis for block dissection. FNAC is accurate and specific when nodes are palpable; in those with impalpable nodes a preliminary MIN biopsy followed by SNB if the MIN biopsy is negative will accurately select all patients with metastases in the groin nodes. This can be performed by examining frozen sections of the lymph nodes; if positive, block dissection can be carried out at the same time.     

Efficacy of sonographically guided biopsy of thyroid masses and cervical lymph nodes

OBJECTIVE: We performed a prospective study in 96 patients to determine accuracy of sonographically guided fine-needle aspiration biopsy of thyroid masses and cervical lymph nodes. MATERIALS AND METHODS: Real-time sonography was used to guide biopsy of 112 cervical masses in 96 patients (71 patients with impalpable masses, 16 with failed unguided attempts, patient's or physician's preference in nine). The diameters of all masses were less than 3 cm, with a mean of 1.5 cm and a median of 1.5 cm. Twenty-nine masses measured 1 cm or less in diameter, 60 masses between 1.1 and 2.0 cm, and 23 masses between 2.1 and 3.0 cm. Cervical masses that were sampled by biopsy included 75 thyroid masses and 37 lymph nodes. RESULTS: Diagnostic specimens were obtained in 102 (91%) of 112 masses sampled. Sixty-eight (91%) of 75 biopsies of thyroid tissue and 34 (92%) of 37 biopsies of lymph nodes were diagnostic. Nondiagnostic thyroid biopsies included four of complex cysts and three of solid nodules. Sonographic follow-up (1 year) revealed no change or decrease in size of those seven lesions. Sixty of 68 diagnostic thyroid biopsies showed benign processes: 42 macrofollicular adenomas, six colloid adenomas, five microfollicular adenomas, four probable cases of thyroiditis, and three hemorrhagic cysts. The remaining eight diagnostic thyroid biopsies showed malignant processes: seven papillary carcinomas and one metastatic small-cell carcinoma. Of 34 diagnostic biopsies of lymph nodes, 26 showed malignant processes and eight showed benign processes. Surgery in the three patients with nondiagnostic biopsies of lymph nodes revealed two recurrent medullary cancers and one benign node. CONCLUSION: Sonographically guided fine-needle aspiration biopsy of neck masses has a high sensitivity (91%) and should be routinely used to evaluate indeterminate masses in the neck.     

Positron emission tomography in diagnosis of occult adenocarcinoma of the breast

Occult adenocarcinoma with clinically apparent axillary lymphadenopathy represents a challenging surgical problem. Mammography is frequently unable to identify a primary breast carcinoma, and extramammary sources are common and equally difficult to identify. This may leave the clinician and patient with a conundrum of whether to proceed with "blind" mastectomy. A 35-year-old white female presented with axillary adenopathy and a normal breast physical exam. Mammography was unable to demonstrate a specific tumor. Excisional biopsy of the axillary lymph node demonstrated metastatic adenocarcinoma. Positron emission tomography showed increased uptake in the breast and the axilla, consistent with breast carcinoma and axillary metastases. The patient underwent modified radical mastectomy and pathologic review of the specimen proved infiltrating ductal carcinoma in the breast with metastatic nodes. Positron emission tomography may be helpful in localizing occult carcinoma of the breast that presents with metastatic lymph nodes and in excluding other potential primaries.     

Changes of autonomic tone before the onset of paroxysmal atrial fibrillation

BACKGROUND: Sentinel node (SN) biopsy appears to offer an alternative to routine axillary lymph node dissection (ALND) for staging patients with breast cancer. Various techniques have been studied for identifying the SN, using vital blue dye or radioactive colloid, and initial reports are promising. The inherent limitations and pitfalls must be clearly understood before SN biopsy can be implemented in dinical practice. STUDY DESIGN: In a prospective trial, the feasibility of using lymphoscintigraphy and gamma probe detection for performing SN biopsy was studied. In 130 consecutive patients with T1-T2, N0 breast cancer, preoperative lymphoscintigraphy was performed with technetium 99m-colloidal albumin. During ALND, the radioactive axillary SNs were localized by the gamma probe. Histopathologic examination of the harvested SNs was compared with the status of the axillary lymph nodes. RESULTS: Axillary focal accumulations were clearly identified on lymphoscintigraphy in 116 patients (89%). The failure rate was significantly higher in patients who had a previous excision biopsy (36%) than in those with a palpable tumor in situ (4%). Using the gamma probe, radiolabeled axillary SNs were successfully biopsied in 122 patients (94%). Because 18 of these patients did not undergo formal lymphadenectomy, the predictive accuracy of SN biopsy was analyzed in 104 patients. Radioactive nodes revealed metastases in 44 of 104 patients (42%); in 26 of them (59%), these were the only involved axillary nodes. The SN was negative in 60 patients (58%); in one patient the ALND was found to contain metastatic disease (1.7% false negatives). Biopsy of the SN was 98% accurate in predicting the absence of nodal metastases. CONCLUSIONS: There are certain guidelines for performing SN biopsy by lymphoscintigraphy and gamma probe detection. Success depends primarily on an adequate functional capacity of the SN, necessary for sufficient nodal uptake to ensure accurate identification. Lymphoscintigraphy defines the pattern of lymph flow and may prevent failure or false-negative biopsies. Biopsy of the SN is a highly accurate, minimally invasive method of staging patients with breast cancer and can substantially reduce the morbidity and costs of surgical treatment by avoiding unnecessary ALND in the majority of patients.     

Gamma-probe-guided resection of the sentinel lymph node in breast cancer

Regional lymph node metastases in patients with breast cancer have fundamental staging, prognostic, and treatment implications. Classically, axillary lymph node sampling requires a dissection under general anesthesia. The concept that a primary, or sentinel, lymph node is the first node to receive drainage from a tumor has been established in patients with malignant melanomas using radiolabeled tracers and vital dyes. This study proposed two hypotheses: (1) radiolabeled sentinel lymph nodes can be identified in most patients with breast cancer, and (2) radiolabeled sentinel lymph node biopsy accurately predicts axillary lymph node metastases in those patients. Patients with operable breast cancer had Tc-99 sulphur colloid injected around their breast tumors 1-6 hours preoperatively. Patients underwent gamma probe identification of sentinel lymph nodes that were biopsied. All patients underwent axillary lymphadenectomy in conjunction with lumpectomy or mastectomy. Fifty female patients ages 26 to 90 years underwent lumpectomies with axillary dissections (40 patients) or modified radical mastectomies (10 patients). Sentinel lymph nodes were identified in 42 of 50 patients (84%). Eight patients (16%) had metastases to the axillary lymph nodes. In 7 patients, sentinel lymph nodes correctly predicted the status of the axillary nodes. There was one false negative result. A total of 550 lymph nodes were resected for an average of 11.2 nodes per patient. Sentinel lymph node scintigraphy and biopsy accurately predicted the axillary lymph node status in 41 of 42 patients (98%). Scintigraphy can identify sentinel lymph nodes in a large majority of patients. Sentinel lymph node biopsy is an accurate predictor of axillary lymphatic metastases.     

Comparison of oncogene mutation detection and telomerase activity for the molecular staging of non-small cell lung cancer

Novel oncogene mutation detection techniques have demonstrated that standard histopathological examination may fail to detect clinically significant metastatic cancer cells. Recently, telomerase activity has been detected in most immortal cell lines and human tumors, potentially providing a novel diagnostic marker. We compared standard histopathological examination with the telomeric repeat amplification protocol assay and either a p53 plaque hybridization or a K-ras mutation ligation assay in the lymph nodes of 12 patents with surgically resectable non-small cell lung cancer. Telomerase activity was detected in 10 of 10 (100%) evaluable tumors. Eight of 9 (89%) histopathologically positive lymph nodes were telomerase positive, and 26 of 48 (54%) histopathologically negative lymph nodes were telomerase positive. In comparison, oligonucleotide plaque hybridization detected metastases in all 3 histopathologically positive nodes and in 3 of 27 histopathologically negative nodes. Similarly, the K-ras mutation ligation assay detected metastases in all 6 histopathologically positive lymph nodes examined and in 1 of 21 histopathologically negative lymph nodes. Thus, most of the "positive" nodes by telomerase assay did not harbor occult neoplastic cells that shared the same genetic alteration as the primary tumor. The high rate of false positives associated with the telomeric repeat amplification protocol assay limits its role in staging lymph nodes in patients with non-small cell lung cancer.     

Reliability of multimodal evaluation of abnormal screening mammogram results

OBJECTIVE: Our purpose was to evaluate the effectiveness and reliability of the multimodal evaluation of suspicious or equivocal screening mammogram results by use of ancillary imaging studies and needle biopsies. STUDY DESIGN: This article reports on the experience of the Breast Evaluation Center at Long Beach Memorial Medical Center between 1989 and 1993 where 43,125 screening mammograms were performed. RESULTS: A total of 2866 patients were called back for additional evaluation, which consisted of magnification views and ultrasonography. Since 1990 fine-needle biopsies have been done on selected patients and since 1992 core biopsies have been available. Needle localization excisional biopsies were performed on 344 patients, and 158 cancers were diagnosed. This represents a 46% positive predictive value. Careful follow-up was obtained on the patients seen in 1990 to attempt to determine whether any cancers developed within a year of the time the patients with abnormal screening mammogram results had been evaluated with imaging modalities but no tissue diagnosis made. One cancer may have been missed. The cost savings of this protocol are also examined. CONCLUSION: Multimodal evaluation of patients with suspicious screening mammogram results appears to be a cost effective approach with adequate sensitivity and specificity.     

Staging of breast cancer: what standards should be used in research and clinical practice?

BACKGROUND: Bone scan (BS), chest X-rays (CXR), liver ultrasonography (LUS) and laboratory parameters (LP) are frequently used as routine staging procedures for breast cancer patients. These procedures are not always appropriate in either clinical or research settings, regardless of the stage. The aim of this study was to identify groups of patients with differing risks for metastases in order to select more precise standard staging procedures. PATIENTS AND METHODS: The staging data relating to 406 breast cancer patients consecutively referred to our institution between November 1989 and October 1996 were analysed including pathological TNN grading and biological parameters. All of the cases with a positive or suspicious pre-operatory staging and who proved to have metastatic disease before surgery or during the first six months of follow-up were considered true-positive; all of the other cases with a positive or suspicious initial staging but with no evidence of distant metastasis before surgery and with a disease-free survival longer then six months were considered false-positive. In the same way all cases with negative initial staging who relapsed during the first six months of follow-up were considered false-negative and those with negative initial staging and with a disease-free survival longer then six months were considered true-negative. Statistical analysis was performed using Fisher's exact test. RESULTS: BS, CXR and LUS, 388, 399 and 398 examinations respectively, were considered available, and 17 (4.38%), six (1.5%) and four (1%), respectively, proved to be true-positive. A statistically significant difference was observed when our cases were grouped according to T status (T4 vs. T1-T2-T3, P < 0.01) and nodal status (N0-N1 cases with less than three involved nodes and N1 with more than three positive lymph nodes N2 patients, P < 0.01). CONCLUSIONS: The present study suggests that breast cancer patients can be divided into three subgroups with different detection rates for distant metastases at staging (0.59%, 2.94% and 15.53%), and that the standard practice should be changed. In the first (T1N0 and T1N1 patients with < or = 3 positive lymph nodes--41.13% of the patients) and the second group (T2N0, T2N1 with < or = 3 positive lymph nodes, T3N0 and T3N1 patients with < or = 3 positive lymph nodes--33.49% of the patients) there is no need for a complete set of staging procedures, whereas full procedural staging is needed in the third group of patients (T4, N1 with > 3 lymph nodes and N2, 25.37% of the patients).     

Cyclin D1, another molecule of the year?

AIM: Testicular germ cell tumours may present as metastases in cervical lymph nodes, yet the primary tumours remain clinically occult. The aim of the study is to alert pathologists and clinicians to this uncommon but important presentation and highlight the clues and the diagnostic adjuncts to its correct diagnosis. METHODS: The clinical, cytological, histological, and immunohistochemical features of two patients with germ cell tumour initially presenting as cervical lymphadenopathy were described and analysed. RESULTS: Both patients were young adult males, who were found to have metastatic undifferentiated carcinoma on fine needle aspiration of the enlarged cervical lymph nodes. The tumour cells in both cases were positive for placental alkaline phosphatase (PLAP) and negative for epithelial membrane antigen (EMA). CONCLUSIONS: Clinicians and pathologists should be aware of the possibility of germ cell tumour when encountering a young adult male with metastatic poorly differentiated carcinoma. Positivity for PLAP and negativity for EMA are helpful adjuncts in arriving at the correct diagnosis.     

Clinical evaluation of cytological diagnosis of nasopharyngeal malignancies

Between 1970 and 1975 cytological examination was applied to the diagnosis of nasopharyngeal malignancies in a series of 216 consecutive patients who had either a tumour in the nasopharynx or clinical signs of nasopharyngeal carcinoma, or who were locally asymptomatic but had enlarged cervical lymph nodes. Smears were taken by introducing a small rough pad of compressed gauze through the mouth into the nasopharynx with an upward-angled forceps. In each case the cytological smear was taken immediately before biopsy; often, a lymph node was removed subsequently. When morphological diagnoses were doubtful and histological findings were at variance with positive cytological findings, the patients were reexamined clinically, and diagnosis was postponed. The case material was made up of 90 nasopharyngeal carcinomas, 24 lymphomas, one malignant melanoma, one adenoid cystic carcinoma and 100 patients without malignancies. Cytological findings from the first smear were positive in 77.8% of nasopharyngeal carcinomas, in 66.6% of lymphomas and in the cases of melanoma and adenoid cystic carcinoma. There were no false-positive results. When the nasopharyngeal carcinomas were subdivided into undifferentiated carcinomas of the nasopharyngeal type and squamous-cell carcinomas, cytological findings were positive in ,0% and 73%, respectively. Positivity of histological findings was distributed as follows: 91.7% for malignant lymphomas, 86.6% for undifferentiated carcinomas and 86.6% for squamous-cell carcinomas. With respect to clinical suspicion of malignancy, positive cytological findings were obtained in 50% of clinically occult cases and in 84.6% of patients with obvious malignancies; intermediate figures were found for clinically doubtful (64.3%) and for highly suspicious (77.8%) cases. Cyto-histological concordance was shown in 70% of cases; false-negative histological results were obtained in 7.8% and false-negative cytological results in 16.6% of cases. Combined cyto-histological positive results allowed diagnostic accuracy from the first samples in 94.4% of cases. Undifferentiated carcinoma appeared to be the malignancy most accessible to cytological diagnosis, with positive results ranging from 65% in clinically negative or doubtful cases to 84.5% in those with obvious tumours. Assessment of the cytology of the nasopharynx, using the new sampling method described herein, may be a useful diagnostic tool in nasopharyngeal maliganancies.