Long-term results of ultrasound guided fine needle aspiration cytology in conjunction with sentinel node biopsy support step-wise approach in melanoma.

BACKGROUND: US-FNAC is a common diagnostic tool in the work-up of many cancers. Results in melanoma were initially poor (sensitivity 20-40%). Introduction of the Berlin Morphology criteria has shown potential improvement up to 65-80% in selected patients. AIM: This cohort study evaluates the long-term survival outcome of melanoma patients undergoing Ultrasound (US) guided Fine Needle Aspiration Cytology (FNAC) prior to sentinel node biopsy (SNB) or direct lymphadenectomy. METHODS: Between 2001 and 2010 over 1000 consecutive melanoma patients prospectively underwent targeted US-FNAC prior to SNB. The Berlin US morphology criteria: peripheral perfusion (PP), loss of central echoes (LCE) and balloon shape (BS) were registered. FNAC was performed if any factor was present. All patients underwent SNB or lymphadenectomy in case of positive FNAC. RESULTS: Median follow-up was 61 months (IQR 40-95). SN positivity rate was 21%. Survival analyses demonstrated that patients with positive US-FNAC had poor survival. After adjustment for SN status and other known prognostic features, patients with positive US-FNAC (hazard ratio (HR) 1.80, 95% CI 1.10-2.96) had worse survival than patients with normal US (reference). Patients with suspicious US and negative FNAC (HR 1.13, 95% CI 0.71-1.78) had survival comparable to patients with normal US. CONCLUSIONS: The long-term US-FNAC results support this step-wise approach to melanoma patients. Patients with positive US-FNAC have a poor survival and can be spared a SNB. Patients with suspicious US and negative FNAC should undergo SNB to detect microscopic occult disease. Completely US-FNAC negative patients might only require follow-up and no SN staging at all.

The interval between primary melanoma excision and sentinel node biopsy is not associated with survival in sentinel node positive patients - An EORTC Melanoma Group study.

BACKGROUND: Worldwide, sentinel node biopsy (SNB) is the recommended staging procedure for stage I/II melanoma. Most melanoma guidelines recommend re-excision plus SNB as soon as possible after primary excision. To date, there is no evidence to support this timeframe. AIM: To determine melanoma specific survival (MSS) for time intervals between excisional biopsy and SNB in SNB positive patients. METHODS: Between 1993 and 2008, 1080 patients were diagnosed with a positive SNB in nine Melanoma Group centers. We selected 1015 patients (94%) with known excisional biopsy date. Time interval was calculated from primary excision until SNB. Kaplan-Meier estimated MSS was calculated for different cutoff values. Multivariable analysis was performed to correct for known prognostic factors. RESULTS: Median age was 51 years (Inter Quartile Range (IQR) 40-62 years), 535 (53%) were men, 603 (59%) primary tumors were located on extremities. Median Breslow thickness was 3.00 mm (IQR 1.90-4.80 mm), 442 (44%) were ulcerated. Median follow-up was 36 months (IQR 20-62 months). Median time interval was 47 days (IQR 32-63 days). Median Breslow thickness was equal for both <47 days and ≥47 days interval: 3.00 mm (1.90-5.00 mm) vs 3.00 mm (1.90-4.43 mm) (p = 0.402). Sentinel node tumor burden was significantly higher in patients operated ≥47 days (p = 0.005). Univariate survival was not significantly different for median time interval. Multivariable analysis confirmed that time interval was no independent prognostic factor for MSS. CONCLUSIONS: Time interval from primary melanoma excision until SNB was no prognostic factor for MSS in this SNB positive cohort. This information can be used to counsel patients.

[Sonographic criteria for diagnosing sentinel node metastases in melanoma patients]. / Sonografische Kriterien zur Diagnostik von Metastasen im Sentinel-Lymphknoten bei Patienten mit malignem Melanom.

PURPOSE: Ultrasound-guided fine needle aspiration cytology (US-FNAC) prior to surgical excision of a sentinel lymph node (SLN) is a new microinvasive approach for detecting micrometastases in melanoma patients. The aim of the current prospective study was to determine the sensitivity and specificity of the method and to define new diagnostic generally applicable ultrasound criteria. MATERIALS AND METHODS: In 800 consecutive patients suffering from malignant melanoma of stage I/II, the SNs were examined sonographically after lymphoscintigraphy. US-FNAC was performed in all suspicious lesions in 302 patients. All patients underwent surgical removal of the SLN. The final histopathology and sonographic findings were correlated. RESULTS: After a follow-up of 37 months and a given median tumor thickness of 1.6 mm in our cohort, 21 % of the patients had a positive SLN in the histologic examination. We calculated a sensitivity and specificity of US-FNAC of 56 % and 99 %, respectively. The positive and negative predictive values were 92 % and 89 %, respectively. The highest positive predictive values were achieved using the ultrasound criterion of peripheral perfusion in power mode. The sensitivity of US-FNAC increased in parallel with an increasing pT stage of the primary tumor and increasing size of the largest diameter of the involved SN nest. CONCLUSION: Our prospective study shows the impact of ultrasound-guided FNAC in the staging of the SN prior to a planned SLNB. It proved to be an additional, cost-effective diagnostic tool that enhances the discriminatory power for the indication to perform SLNB and spares both the patient and the surgeon a second surgical procedure. Among the tested ultrasound criteria, peripheral perfusion (PP) showed the highest sensitivity for detecting early SN.

[Surgical technique and postoperative morbidity following radical inguinal/iliacal lymph node dissection--a prospective study in 67 patients with malignant melanoma metastatic to the groin]. / Technik und Morbidität der radikalen inguinal / iliakalen Lymphknoten-dissektion--eine prospektive Untersuchung an 67 Patienten mit lymphogen metastasiertem malignen Melanom.

BACKGROUND: The surgical radical inguinal / iliacal lymph node dissection (RLND) is the procedure of choice in patients presenting with lymphatic metastasis of melanoma of the lower extremity or the lower part of the trunk. The perioperative morbidity of patients includes not only local wound complications, seroma formation or lymphatic fistula but also leg oedema, deep venous thrombosis and neuralgic disorders postoperatively. The aim of this prospective study was the evaluation of postoperative morbidity in patients undergoing radical inguinal/iliacal RLND in a standardised surgical fashion. PATIENTS AND METHODS: 67 patients suffering from malignant melanoma of the lower extremity or the lower trunk with metastatic lymph nodes in the groin or the iliacal region underwent a combined RLND of the inguinal / iliacal region or the groin alone between 2003 and 2006. All operations were performed in a standardised technique. The main criterion of the study was the incidence of postoperative wound complications. Minor endpoints included the incidence of lymphatic fistula, the length of hospital stay, and the development of temporary or permanent leg oedema. RESULTS: 64 patients underwent inguinal / iliacal and 3 patients only inguinal LND (lymph node dissection). All patients tolerated the procedure well. The overall wound complication rate was 34 %. One patient died on the 21st postoperative day due to a pulmonary embolism and a simultaneous cerebral apoplexy. Lymphatic fistula occurred in 22 (33 %) patients whereas seroma resulted in 23 (34 %) patients. The length of hospital stay was 15 (3-41) days. A relevant leg oedema was observed in 9 (13 %) patients. CONCLUSION: Even with a proper perioperative management and a precise wound care management, one-third of the patients undergoing radical inguinal / iliacal lymphadenectomy suffer from a complication requiring medical or interventional treatment. Our data demonstrate that most of these complications can be treated sufficiently by conservative treatment. A fitted surgical support hose could prevent long-term complications.

Primary carcinoma of ectopic axillary breast tissue.

The presence of ectopic breast tissue is reported in 2-6% of the general population with most cases being located in the axillary region. Although the same pathology occurs in both eutopic and ectopic breast tissue, primary carcinoma of ectopic breast tissue has been reported only in a small number of cases. Because an overlying accessory areola or nipple is often missing and because of a general lack of awareness among physicians and patients concerning these unsuspicious nodules, clinical diagnosis is frequently delayed. Histological diagnosis can also be delayed if ectopic breast tissue is not present or screened for in the biopsy specimens as apocrine glands of the breast and skin, respectively, exhibit striking similarities and immunohistochemistry is of limited help. Diagnostic delay is demonstrated by the case of a 56-year-old patient who underwent a series of four surgical excisions of a primary ectopic breast carcinoma and developed local lymph node metastasis until treatment with tamoxifen was started. As two-thirds of reported cases of primary ectopic breast carcinoma arose within the axillae, this case underlines the importance of a search for ectopic breast tissue in the context of axillary ductal carcinoma.

Systemic eight-cycle anti-CD20 monoclonal antibody (rituximab) therapy in primary cutaneous B-cell lymphomas--an applicational observation.

BACKGROUND: Primary cutaneous B-cell lymphomas (PCBCLs) are characterized by restriction to the skin and a variable but mostly favourable prognosis. Since 1997 the recombinant, chimeric anti-CD20 antibody rituximab has been used in patients suffering from non-Hodgkin's B-cell lymphomas. Different studies have shown that the effectiveness and safety in the treatment of patients with low-grade follicular lymphoma is comparable to or even higher than the standard CHOP chemotherapy. So far it has been unclear whether an extended duration of therapy leads to a benefit for the patients with PCBCL. OBJECTIVES: To evaluate the objective response rate, time to progression, remission quality and histological changes and to compare our data with the literature. PATIENTS/METHODS: Ten patients with PCBCL [eight with follicle centre cell lymphoma (FCCL), one with marginal zone lymphoma (MZL) and one with diffuse large B-cell lymphoma of the leg (DLBCL)] were treated by intravenous application of a chimeric antibody against the CD20 transmembrane antigen (rituximab) with a dosage of eight cycles, 375 mg m(-2) body surface, weekly. RESULTS: The treatment regimen resulted in clinical overall response in 9 of 10 patients, in particular there were seven complete responses (70%) plus two partial responses (20%). The median duration of remission (durable remission, DR) is 23 months (4-30 months) to date. Histological assessment of responses in four patients showed no tumour-specific infiltration. In two patients histology revealed a residual infiltration and in one patient an increasing infiltration. In two patients no histology was taken after treatment; one patient developed a new lesion. No severe side-effects occurred. Observed side-effects were two bacterial infections, two patients with shivering during infusion, one patient with sweating for months and one patient with persisting itching. As expected the B-cell count in peripheral blood was depressed in all patients after infusion. CONCLUSIONS: Intravenous therapy with eight cycles of the anti-CD20 antibody rituximab is a non-toxic and effective treatment for a subset of patients with PCBCL (relapsed, aggressive entity, old patients, multiple lesions) with a long DR.

Cowden disease: CT findings in three patients.

Cowden disease, also known as multiple hamartoma syndromes, is an autosomal dominant disease characterized by numerous benign mucocutaneous tumors, hamartomas of multiple organs, and malignancies of the breast and thyroid. In this report, we present the computed tomographic findings in three patients with Cowden disease. In addition to the classic findings, the patients were diagnosed with spinal neurinoma (n=1), meningioma (n=1), and hepatic hemangioma (n=3). We also review current clinical and genetic concepts that unify Cowden disease.

Antitumour activity of paclitaxel and interferon-alpha in a case of metastatic eccrine porocarcinoma.

BACKGROUND: Eccrine porocarcinoma (EP) is a rare malignant tumour arising in the acrosyringium, with about 50% of the cases developing local recurrence or metastatic disease. No standard therapy protocols for metastatic disease exist. In the past, only short remissions were achieved by applying combinations of cytotoxic agents, which were associated with severe side-effects. AIM OF THE STUDY: In the case reported here, the aim was to find a protocol with fewer side-effects for a patient who was not willing to undergo extensive polychemotherapy. SUBJECT: A 67-year-old male patient with local recurrence and regional lymph node metastases after resection of EP was treated with a combination of interferon-alpha (IFN-alpha) 9 million units s.c. three times per week and paclitaxel 100 mg/m(2) weekly i.v., which shows a side-effect profile similar to taxotere and is used in the treatment of a variety of neoplasms such as advanced squamous cell carcinoma. MAIN OUTCOME: This less aggressive treatment was tolerated well and the patient responded with minor remission and long-term stable disease.

Malignant melanoma arising in a radiotherapy field: report of two cases and review of the literature.

We report 2 patients who developed melanoma or melanoma metastases in radiation fields 6 and 43 years after radiation therapy, respectively. One of the patients had received adjuvant hyperfractionated photon therapy for Ewing sarcoma, while the other patient had received X-ray therapy for a hemangioma. While postradiation secondary cancers with a long latency period are not uncommon, the development of melanoma is exceedingly rare.

Chronic indurated ulceration of the leg, epithelioid sarcoma with lymph node metastasis.

Epithelioid sarcoma is a seldom seen tumor characterized by an innocuous presentation of a non tender nodule or cluster of nodules located on a distal extremity with a high propensity for nodal spread as well as relentless local progression. We describe a patient with the neoplasm masquerading as chronic leg ulcers of unknown origin with an unusual immunohistochemical profile. The difficulty of timely clinical and histological diagnosis is a key problem encountered. Better awareness may result in earlier diagnosis and improved prognosis.

Prognostic factors for survival and factors associated with long-term remission in patients with advanced melanoma receiving cytokine-based treatments: second analysis of a randomised EORTC Melanoma Group trial comparing interferon-alpha2a (IFNalpha) and interleukin 2 (IL-2) with or without cisplatin.

The aim of this study was to define prognostic factors for survival, and especially for long-term survival in a mature data-set of patients with stage IV melanoma treated within a randomised trial of cytokine-based protocols. Long-term follow-up data on patients enrolled into a European Organization for Research and Treatment of Cancer (EORTC) trial comparing interferon-alpha (IFNalpha) plus interleukin-2 (IL-2) with or without cisplatin were collected. Univariate and multivariate Cox regression analyses were performed to define prognostic factors for survival. The characteristics of patients alive at 2 and 5 years after randomisation were compared with the entire cohort using the chi(2) test. The minimum potential follow-up of the 131 evaluable patients was 5 years. 18 patients (14%) were alive 2 years after randomisation, and 11 (8%) 5 years after randomisation. Pretreatment performance status (PS), serum lactate dehydrogenase (LDH) and tumour mass were significant predictors for survival, whereas site of metastases and number of sites were non-significant. PS and LDH were the only independent prognostic factors. All except 1 patient alive at 2 and 5 years had a pretreatment PS of 100%, and only three long-term survivors had elevated pretreatment LDH. There was no association between the site of metastases and long-term survival. Response to treatment was a major predictor for long-term survival, whereas addition of cisplatin did not impact upon overall survival probability or on long-term survival. The probability of long-term survival in stage IV melanoma patients after IL-2-based treatments is governed by pretreatment PS, serum LDH and response to treatment. Site of metastases, the basis for the M-subcategories of the new AJCC staging system, was not informative in this study.

Efficacy of ultrasound B-scan compared with physical examination in follow-up of melanoma patients.

BACKGROUND: The value of ultrasound B-scan for routine follow-up of melanoma patients still is not generally accepted. Therefore, the authors compared the efficacy of physical examination (PE) with ultrasound B-scan (UBS) for detection of regional tumor recurrence in melanoma patients. The aim of the current study was to evaluate whether early detection of metastases improves relapse-free and overall survival. METHODS: For a period of 4 years, 829 consecutive melanoma patients were followed prospectively. Physical examination of 3011 patients and concomitant UBS of in-transit routes and regional lymph node basins were performed. Suspicious lesions were diagnosed by fine-needle aspiration cytology and pathology. RESULTS: During the study period, 242 (90.6%) of 267 patients with melanoma recurrences were first recognized by PE or UBS within the routine follow-up program. The sensitivities of both methods differed significantly (P = 0.001). Metastases were detected by PE in only 61 of 242 recurrences (25.2%, 95% confidence interval [CI]: 19.9-31.2%), whereas UBS revealed 240 recurrences (99.2%, 95% CI: 97.3-99.6%). The specificity was 98.4% (95% CI: 97.8-98.8%) and 98.3% (95% CI: 97.7-98.7%), respectively. Survival of 103 patients who presented with a first nodal melanoma recurrence was followed and analyzed by multiple Cox regression. Overall survival was affected by the diameter of the largest metastasis (P = 0.001) and the number of metastatic lesions (P = 0.012). CONCLUSION: The study found that ultrasound B-scan was highly effective in the early detection of regional melanoma metastases compared with physical examination. Earlier detection of such metastases seemed to result in improved overall survival.

Ultrasound in dermatology. Part II. Ultrasound of regional lymph node basins and subcutaneous tumours.

Ultrasound in dermatology is a non-invasive tool for the detection and verification of tumours in skin, subcutaneous tissues and in lymph node basins. Since the introduction of ultrasound examination in the routine practice of dermatology in the late seventies [1], ultrasound has evolved to become a standard diagnostic method, at least in Europe. Subcutaneous or regional nodal metastases or benign tumours or tissue accumulation may not be palpable due to small size, distance from the skin surface or location in an area of postoperative or radiation fibrosis, which renders a physical examination on its own difficult. Palpation even by an experienced physician is also known to be an inaccurate technique for the assessment of lesions in head and neck cancer [2] as well as in scar tissue. Ultrasound, on the contrary is able to give additional and reliable information about the exact position of a tumour, surrounding anatomical structures, the dimension of the lesion in two perpendicular diameters in mm, its echo pattern as well as the distance from the skin surface. High resolution ultrasound technique is not only able to detect small targets (< 3 mm), but also to predict difficulties in the surgical search for metastases due to a deep subcutaneous or intramuscular position, or a localization near structures (e.g. vessels) which could easily be traumatized. Several invasive and non-invasive staging tools have been developed for the detection of regional disease or tumours in the soft tissue to support the often ineffective physical examination on its own. Among these techniques, ultrasound has been proven to have superior sensitivity to physical examination in the detection of regional metastases in melanoma patients [3-6] as well as in hematology and oncology patients [7] and it even facilitates the surgical management of such patients [8-10]. Based on technical equipment and clinical requirements, ultrasound used in dermatology is performed using frequencies between 7.5 and 15 MHz. Additionally duplex and colour flow analysis may complement grey-scale ultrasound by demonstrating tumour vascularity and characterising masses [11, 12]. In this part of the two CME articles on ultrasound we want to illustrate the most important technical details, procedural steps and the clinical use of high-frequency ultrasound in dermatology.

Presurgical ultrasound-guided anchor-wire marking of soft tissue metastases in stage III melanoma patients.

BACKGROUND: Due to increased sensitivity of diagnostic procedures, soft tissue metastases in melanoma patients are frequently detected very early. However, small sizes, deep location, or position close to vulnerable structures could render subsequent surgery quite difficult. OBJECTIVE: To test the feasibility and effectiveness of presurgical ultrasound-guided anchor-wire marking of melanoma metastases. METHODS: We selected melanoma patients with cytologically proven metastases in clinical stage III which were either unfavorably located or which have failed removal by previous surgery. Anchor-wire marking was performed ultrasound guided and free-hand style without the use of local anesthesia. RESULTS: Twelve procedures in nine patients were well tolerated without any complications. In 11 cases the wire tip proved to be located within the tumor lesion; in one case the wire tip missed the target by less than 5 mm and thus was close enough to support appropriate surgery. Earlier, 3 of the 12 study lesions had undergone unsuccessful surgery. The median diameter of the removed metastases was 18.5 mm (range 7-30 mm). CONCLUSION: Ultrasound-guided anchor-wire marking of unfavorably located melanoma metastases is feasible and might facilitate subsequent surgery.

[Ultrasound-guided fine needle aspiration cytology (FNAC) of unclear lesions in melanoma patients]. / Ultraschallunterstützte Feinnadelaspirationszytologie (FNAC)unklarer Raumforderungen bei Melanompatienten.

AIM: Fine needle aspiration cytology (FNAC) is widely used in oncology to obtain the diagnosis of unclear tumours in cancer patients. However, because the method is established only in few melanoma centers, we performed this study to evaluate ultrasound guided FNAC in routine follow-up of melanoma patients. METHOD: Unclear tumours recognised during routine follow-up of melanoma patients underwent ultrasound guided fine needle aspiration with cytological examination. The results were then compared to subsequent histopathology or future clinical outcome. RESULTS: 275 unclear tumours received ultrasound guided fine needle aspiration with cytological examination. Sensitivity showed to be 95.6% [95% CI: 91.5-98.1], specificity was 100% [95% CI: 96.2-100.0]. The positive predictive value was 100.0% [95% CI: 97.9-100.0], the negative predictive value 92.2% [95% CI: 85.1%-96.9%]. In 89 cases lesions turned out to be cytologically benign thus diagnosis avoiding surgery. In lesions with diameters up to 10 mm sensitivity and specificity were 91.4% and 100.0%, respectively. CONCLUSION: Ultrasound guided FNAC proved to be a minimal invasive procedure in the diagnosis of unclear tumours in the follow-up of melanoma patients. It allows definite diagnosis and avoids unnecessary diagnostic surgery.

Ultrasound-guided fine-needle aspiration cytology in the early detection of melanoma metastases.

BACKGROUND: The early detection and treatment of tumor recurrences in melanoma patients is dependent on reliable, sensitive, and specific techniques to verify suspected tumor metastases. As of now, fine-needle aspiration cytology (FNAC) has yet to establish itself in the routine follow-up of melanoma patients. METHODS: FNAC procedures were performed in melanoma patients with palpable tumors or nonpalpable, ultrasonically suspicious lesions. Cytodiagnostic evaluation of fine-needle samples obtained from suspicious lesions was performed morphologically. Findings were validated either by histopathologic diagnosis or prolonged clinical follow-up. RESULTS: The cytologic examination of 739 FNACs from 330 melanoma patients was conducted within 1 day of sampling. Complications were not observed. This study showed a sensitivity of 97.9% and a specificity of 100.0%. Moreover, in 158 FNACs derived from lesions with a diameter less than 1 cm a sensitivity of 94.6% was achieved. Diagnosis of metastatic melanoma with unknown primary tumor was established in 20 cases. CONCLUSIONS: FNAC is very reliable for the early detection of melanoma metastases. FNAC is a swift method free of complications and is able to replace diagnostic surgery completely for nonmalignant lesions in a large number of patients. Moreover, FNAC is especially useful in combination with ultrasound in melanoma follow-up and can enable diagnosis of lesions smaller than 1 cm without impairment of sensitivity or specificity.

Correlation of positive RT-PCR for tyrosinase in peripheral blood of malignant melanoma patients with clinical stage, survival and other risk factors.

The clinical value of the reverse transcription polymerase chain reaction (RT-PCR) assay for tyrosinase in peripheral blood of melanoma patients is still under debate. A total of 212 blood samples from 212 melanoma patients in all clinical stages (AJCC) were examined. Erythrocytes were lysed prior to RNA extraction by phenol precipitation from 2.7 ml of blood. cDNA for tyrosinase PCR was synthesized using random hexamers. Positive tyrosinase RT-PCR results were obtained in 11% of 106 stage I patients, 18% of 56 stage II patients, 31% of 26 stage III patients and 67% of 24 stage IV patients. After a median follow-up of 36 months (range 26-41), stage III patients with positive RT-PCR for tyrosinase had a shortened disease-free interval as compared to negative patients (P < 0.01). In stage IV patients, median overall survival was 8 months in case of a positive RT-PCR in contrast to 12 months in case of a negative test. While univariate analysis showed sex and primary tumour location associated with positive RT-PCR, multiple regression analysis revealed clinical stage and detection of tyrosinase transcripts in peripheral blood as best prognostic factors. Hazard ratios for disease-free survival were 19.7 (confidence interval (CI) 8.53-45.5, P = 0.0001) for metastatic vs primary disease and 2.96 (CI 1.49-5.89, P = 0.002) for positive vs negative tyrosinase RT-PCR. The corresponding hazard ratios for overall survival were 97.0 (CI 12.7-741, P = 0.0001) and 4.33 (CI 1.69-11.1, P= 0.002). Our results emphasize the importance of tyrosinase RT-PCR testing in peripheral blood.

[Endoscopic fasciotomy and subfascial perforator division for chronic stasis ulcers]. / Die endoskopische Fasziotomie mit und ohne Perforansdiszision bei chronischem Ulcus cruris venosum.

Chronic venous ulcer disease is often refractory to conservative treatment modalities. After surgery of the superficial vein system, endoscopic methods can be used for division of incompetent perforators or to perform paratibial fasciotomy in cases of chronic functional compartment syndromes. We report on 13 endoscopically performed paratibial fasciotomies with or without concomitant endoscopic subfascial division of perforators (ESDP) in patients with stasis ulcers present for a median duration of 15 years. In all patients we observed immediate reduction of pain and edema. In 8 of 13 cases the ulcers healed within 3 months, another ulcer healed within 6 months and the remaining 4 ulcers showed a reduction in size of more than 75%. We conclude that endoscopically performed fasciotomy with or without ESDP is highly effective and has its place in the treatment of chronic venous ulcer disease.

Detection of regional melanoma metastases by ultrasound B-scan, cytology or tyrosinase RT-PCR of fine-needle aspirates.

Physical examination and ultrasound B-scan screening are important follow-up procedures in melanoma patients with regional disease. However, they do not allow definite diagnosis of suspicious lesions. Fine-needle aspiration cytology (FNAC) enhances the diagnostic accuracy in such patients but, unfortunately, reaches its technical limits, particularly when very small or necrotic lesions are examined. We therefore tested whether tyrosinase reverse transcription polymerase chain reaction (RT-PCR) of fine-needle aspirates (FNA-PCR) could help to increase diagnostic sensitivity. With clinical follow-up in 69 melanoma patients 81 regional lymph nodes were detected by ultrasound B-scan examination, nine of whom appeared to be palpable. Technically, FNAC was successful in all 81 lymph nodes, while FNA-PCR failed to obtain RNA at detectable levels in two lymph nodes of two patients. Of 79 lesions which have been completely evaluated by B-scan, FNAC and FNA-PCR, 44 proved to be melanoma metastases by histopathology, while the remaining 35 lesions were finally classified as non-specific lymph nodes. Of the 44 melanoma metastases 80% (n = 35) have been detected by B-scan, 90% (n = 39) by FNAC and 100% (n = 44) by FNA-PCR (P < 0.05 vs FNAC, P < 0.005 vs B-scan). In the subclass of lesions with diameters below 10 mm the sensitivities were 72% (n = 13), 78% (n = 14) and 100% (n = 18) respectively. In 35 regional lymph nodes classified as benign lesions, FNAC was always negative while FNA-PCR produced one positive result. Neither of these methods did produce false positive results in 15 control lymph nodes of non-melanoma patients. We conclude, that FNA-PCR might have superior sensitivity as compared to FNAC or ultrasound B-scan, particularly in melanoma lesions with diameters below 10 mm.