Concordance between HER-2 status determined by qPCR in Fine Needle Aspiration Cytology (FNAC) samples compared with IHC and FISH in Core Needle Biopsy (CNB) or surgical specimens in breast cancer patients.

Determining the status of HER2-neu amplification and overexpression in breast cancer is crucial for prognosis but mostly for treatment purposes. Standard techniques include the determination of IHC in combination with in situ hybridization techniques to confirm a HER2-neu amplification in case of IHC2+ using either a core-needle biopsy or a surgical specimen. qPCR has been also demonstrated to be able to determine HER2 status, mostly in core biopsies or in surgical specimens. Fine-needle aspiration is a reliable, quicker and less invasive technique that is widely used for diagnosis of invasive breast cancer. In this study, we assessed the performance of qPCR in invasive breast carcinomas to determine HER2-neu status by using fine-needle aspiration samples and comparing to standard IHC and FISH. From a total of 154 samples from patients who had nodular breast lesions and attended the 1-day-stop clinic at the Gustave Roussy from March 2013 to October 2014, qPCR was able to determine the HER2 status in a mean of 3.7 days (SD 3.1). The overall concordance with standard HER2-testing was very high: 97% (95% CI 0.94 to 0.99); sensitivity was 96% (0.87-1), specificity 98% (0.95-1) and positive and negative predictive values 88% (0.75-1) and 99% (0.98-1), respectively. In conclusion, our study demonstrates that qPCR performed using fine-needle aspiration samples from a primary tumour is a reliable and fast method to determine HER2/neu status in patients with early breast cancer.

The challenge of rapid diagnosis in oncology: Diagnostic accuracy and cost analysis of a large-scale one-stop breast clinic.

PURPOSE: Rapid diagnosis is a key issue in modern oncology, for which one-stop breast clinics are a model. We aimed to assess the diagnosis accuracy and procedure costs of a large-scale one-stop breast clinic. PATIENTS AND METHODS: A total of 10,602 individuals with suspect breast lesions attended the Gustave Roussy's regional one-stop breast clinic between 2004 and 2012. The multidisciplinary clinic uses multimodal imaging together with ultrasonography-guided fine needle aspiration for masses and ultrasonography-guided and stereotactic biopsies as needed. Diagnostic accuracy was assessed by comparing one-stop diagnosis to the consolidated diagnosis obtained after surgery or biopsy or long-term monitoring. The medical cost per patient of the care pathway was assessed from patient-level data collected prospectively. RESULTS: Sixty-nine percent of the patients had masses, while 31% had micro-calcifications or other non-mass lesions. In 75% of the cases (87% of masses), an exact diagnosis could be given on the same day. In the base-case analysis (i.e. considering only benign and malignant lesions at one-stop and at consolidated diagnoses), the sensitivity of the one-stop clinic was 98.4%, specificity 99.8%, positive and negative predictive values 99.7% and 99.0%. In the sensitivity analysis (reclassification of suspect, atypical and undetermined lesions), diagnostic sensitivity varied from 90.3% to 98.5% and specificity varied from 94.3% to 99.8%. The mean medical cost per patient of one-stop diagnostic procedure was €420. CONCLUSIONS: One-stop breast clinic can provide timely and cost-efficient delivery of highly accurate diagnoses and serve as models of care for multiple settings, including rapid screening-linked diagnosis.

Frequency and intensity of pain related to thyroid nodule fine-needle aspiration cytology.

BACKGROUND: Quality of life is an important issue in endocrine tumors because of the high prevalence of benign tumors and the indolent course of most malignant tumors. OBJECTIVE: To evaluate the frequency and the intensity of pain and anxiety in patients undergoing thyroid nodule fine-needle aspiration cytology (FNAC) and to identify factors associated with pain. METHODS: Single center prospective study in the setting of a one-stop outpatient diagnostic clinic for thyroid nodules. Pain was evaluated using a 100-mm visual analogue scale (VAS) immediately following (VAS1) and 30 minutes after (VAS2) FNAC and was considered significant if ≥ 30. Anxiety symptoms were assessed prior to FNAC using a self-report measure questionnaire: the state form of Spielberger State-Trait Anxiety Inventory (STAI, form Y-A). FNAC was performed with a 25-gauge needle and a moderate aspiration and two passes for each nodule. RESULTS: Two hundred eighteen consecutive patients (163 females, 55 males; mean age 53 years, range 12-84 years) undergoing FNAC of one to three nodules were included. VAS1 was ≥ 30 in 24% of the patients and VAS(2) was ≥ 30 in 13% of the patients. Independent significant factors correlated to a VAS1 of ≥ 30 were age under 25 years and the number of nodules being biopsied. Independent significant factors correlated to a VAS2 of ≥ 30 were VAS1 ≥ 30 and female sex. No correlation was found between pain and nodule size or nodule depth, nor the duration of application of the eutectic mixture of local anesthetics (EMLA) patch prior to FNAC. The mean STAI score for anxiety was 37 ± 12. The average STAI score was significantly higher in women (39) than in men (33; p = 0.01). There was no significant correlation between STAI score and age under 25 years, previous FNAC, number of nodules biopsied, or acetaminophen administration, but the STAI score was significantly correlated to VAS1 and VAS2. CONCLUSIONS: FNAC-related pain is frequent and correlates with the number of nodules biopsied, age under 25 years, female sex, and anxiety.

Predicting tumour location in radical prostatectomy specimens: same-patient comparisons of 21-sample versus sextant biopsy.

OBJECTIVE: To determine the value of a 21-sample biopsy protocol in predicting tumour localization in radical prostatectomy (RP) specimens, compared with sextant biopsies. PATIENTS AND METHODS: In all, 300 consecutive patients underwent 21-sample prostate biopsies, followed by RP. The protocol consisted of sextant, three midline, six far lateral and six transitional zone biopsies. Tumour locations on biopsies and RP specimens were compared. The sensitivity, specificity, positive (PPV) and negative predictive value (NPV) and accuracy were calculated. RESULTS: There was no difference between sextant and 21-sample biopsies for sensitivity (38% vs 36%; P=0.50) and specificity (84% vs 87%; P=0.46), but the NPV was higher for 21-sample biopsies (57% vs 68% ; P<0.001). The PPV was higher in the sextant biopsies (74% vs 59%; P=0.007). Sextant, transitional zone and far lateral biopsies were re-grouped in six regions. Compared with 21-sample biopsies, sensitivity (54%) and PPV (79%) were higher (P<0.001), while specificity (74%) and NPV (46%) were lower (P=0.05 and P=0.001, respectively). CONCLUSION: A negative biopsy does not confirm the absence of cancer in the corresponding site in the RP specimen in a sextant or 21-sample biopsy protocol and cannot be used as a prognostic element before RP. A positive biopsy does not always correspond with a tumour in the same zone of the RP specimen. When 21-sample biopsies are re-grouped in to six regions, the value of a positive biopsy increases. A positive biopsy corresponds thus to a tumour in the same region, rather than in precisely the same location. The results of this study could help in the biopsy protocol used for making surgical decisions, e.g. preserving the bladder neck or neurovascular bundles.

High-grade prostatic intraepithelial neoplasia and atypical small acinar proliferation on initial 21-core extended biopsy scheme: incidence and implications for patient care and surveillance.

PURPOSE: To evaluate the incidence of high-grade prostatic intraepithelial neoplasia (HGPIN) and atypical small acinar proliferation (ASAP) in an initial 21-core extended biopsy scheme and to determine the prostate cancer detection rate in the repeated biopsy. METHODS: Between 2002 and 2008, 2,006 patients underwent a first 21-core extended biopsy scheme. Incidences of cancer, ASAP and HGPIN were studied. Cancer detection rate in the repeated 21-core extended biopsy for ASAP and HGPIN was reported and compared with those obtained on repeated biopsy for clinico-biological indications. RESULTS: Incidences of HGPIN and ASAP were 1.7 and 1.1%, respectively. The 6-core and 12-core biopsy schemes detecting HGPIN would have missed the diagnosis of cancer in 10 and 3.6% of cases, compared to a 21-core biopsy protocol, respectively. The cancer detection rate on repeated biopsy for HGPIN was 19% and not significantly different compared with the detection rate on repeated biopsy for clinico-biological indications (16.8%, p = 0.77). Seven prostate cancers were found among the 17 re-biopsies for ASAP revealing a detection rate of 41.2% (p = 0.01). All detected cancers were organ confined. No clinico-pathological data were independent predictor of cancer on repeated biopsy. CONCLUSION: Our report demonstrates the different risk profiles for HGPIN and ASAP in a 21-core extended biopsy scheme. The presence of HGPIN does not imply a higher risk for cancer detection at immediate re-biopsy compared to other patients for whom repeated biopsies were indicated for increasing or persistently increased PSA levels. Repeated biopsy is warranted when ASAP is diagnosed because of a high risk of prostate cancer.

Tubulocystic carcinoma of the kidney: a new entity among renal tumors.

Tubulocystic carcinoma is a tumor entity, which is not yet included in the WHO-classification of renal tumors. We report a series of 11 cases of this tumor, 6 of which were examined in by immunohistochemistry using a panel of five antibodies (CK7, CK34betaE12, CK19, CD10 and P504S). All patients were men. Each had renal tumor stage of pT1N0M0, with a diameter of 1.7 to 7 cm (mean, 3.3 cm). None of the patients presented with recurrence or metastases. Grossly, tumors were microcystic masses with a bubble-wrap appearance. Histological features included cysts and small tubules, separated by delicate septa and lined by flat to columnar or hobnail cells. The cyst and tubule epithelium showed immunohistochemical characteristics of both proximal and distal tubules. Tubulocystic carcinoma is a distinctive kidney tumor, with noteworthy macroscopic and microscopic characteristics, which can be distinguished from other cystic kidney tumors, including cystic nephroma, multilocular cystic renal cell carcinoma and some solid tumors with extensive cystic changes. More cases are needed to ascertain its prognosis. Tubulocystic carcinoma should be considered as a new subtype of renal cell carcinoma in the next revision of the WHO classification.

KIT is highly expressed in adenoid cystic carcinoma of the breast, a basal-like carcinoma associated with a favorable outcome.

Recent biological studies have classified breast carcinomas into HER2-overexpressing, estrogen receptor-positive/luminal, basal- and normal-like groups. According to this new biological classification, the objectives of our study were to assess the clinical, morphologic and immunophenotypic characteristics of adenoid cystic carcinoma of the breast in order to classify this subtype of breast carcinoma. A total of 18 cases of adenoid cystic carcinoma were identified from the Institut Curie files. Clinical information was available for 16 patients with a median follow-up of 6.5 years. Morphologically, all tumors were graded according to the system defined by Kleer and Oberman (histologic and nuclear grade). Immunophenotype was assessed with anti-ER, PR, HER-2, KIT, basal (CK5/6) and luminal cytokeratins (CK8/18) and p63 antibodies. One out of 18 tumors was nuclear grade 1 (16%), nine were nuclear grade 2 (50%) and eight were nuclear grade 3 (44%). All cases were estrogen receptor, progesterone receptor and HER-2 negative. Epithelial cells were strongly positive around glandular lumina with one or both cytokeratins, identifying the coexistence of CK5/6+ cells, CK5/6 and CK8/18+ cells, CK8/18+ cells and p63+ cells. All cases (100%) were also KIT positive. In all, 15 patients were treated by surgery. Nine of them received adjuvant radiotherapy. Follow-up was available for 16 patients. In all, 14 patients were alive. Two of them, initially treated by surgery only, presented a local recurrence. Two patients died (one of them treated by radiation therapy only died from her disease). Our study shows that adenoid cystic carcinoma of the breast is a special, estrogen receptor, progesterone receptor, HER-2 negative and highly KIT-positive, basal-like breast carcinoma, associated with an excellent prognosis. This highly specific immunophenotype could be useful to differentiate adenoid cystic carcinoma of the breast from other subtypes of breast carcinoma such as cribriform carcinoma.

Skin metastases from unknown origin: role of immunohistochemistry in the evaluation of cutaneous metastases of carcinoma of unknown origin.

Determining the primary origin of skin metastases might be a challenging issue for pathologists, especially when there is no primary history or when this history is unavailable. The poor specificity of morphological appreciation is challenging, emphasizing the need for ancillary studies. We have retrieved 44 cases of skin metastases from our pathology files. Paraffin blocks were collected and homemade tissue arrays were made. We have tried to assess the primary origin based on morphological data alone, and then using 13 antibodies (cytokeratins (CK) 5/6, 7, 19, 20, thyroid transcription factor-1, carcinoembryonic antigen, PS100, tumor-associated glycoprotein 72, BerEP4, estrogen receptor (ER), progesterone receptor (PR), CD10, and E-cadherin). Most metastases in our series were from breast (13) and colorectal cancers (six) as they are the main clinical activity in our hospital. Only 44% of cases were correctly assessed based on the sole morphology, emphasizing the need for ancillary studies. CK 20, ER, and PR were the most helpful markers to determine the primary origin of skin metastases by highlighting colorectal origin and mammary origin, respectively. By far, clinical information and morphological evaluation are more reliable than the use of ancillary techniques, which have to be used in the absence of the former one and the poor differentiation of the latter ones. Azoulay S, Adem C, Le Pelletier F, Barete S, Francès C, Capron F. Skin metastases from unknown origin: role of immunohistochemistry in the evaluation of cutaneous metastases of carcinoma of unknown origin.

Pericardial ectopic thymoma.

Primary intrapericardial thymoma is an unusual localization. We report a case of a patient with an isolated and primary pericardial thymoma. This 72-year-old woman presented with dyspnea, dysphony and myalgia. The radiological evaluation revealed an intrapericardial mass. Surgical exploration showed a hemorrhagic and infiltrative tumor in the pericardial sac, while the mediastinum was free of tumor. Surgical biopsies and, later, an ablation of pericardial mass were done. The tumor was a thymoma, composed of large epithelial cells and immature T lymphocytes and was classified B2 according to the World Health Organization classification (1999). Clinically, a myasthenia gravis was revealed. We discuss the few cases reported in the literature.