Immunotherapy in mucosal melanoma: a case report and review of the literature.

BACKGROUND: Mucosal melanoma is a rare form of melanoma presenting variably as sores or unexplained bleeding located mainly in the head and neck region, anorectal region or female genital tract. Mucosal melanoma is usually diagnosed at an advanced stage and is characterized by an aggressive behavior. Surgery represents the mainstay of treatment for early stage melanomas, but for advanced disease there have been until recently very limited treatment options. Ipilimumab, a human monoclonal antibody directed against the cytotoxic T lymphocyte antigen 4, was the first treatment modality to demonstrate survival benefit in advanced malignant melanoma. METHOD: Description of a new case and review of the literature. RESULTS: We present here a patient with mucosal melanoma with aggressive biological behavior and documented late response to ipilimumab. CONCLUSIONS: Ipilimumab represents an effective treatment option in selected patients with mucosal melanoma.

Comparison of lymphatic vessel density and expression of VEGF-C and VEGF-D lymphangiogenic factors in Warthin's tumours and oncocytic adenomas.

OBJECTIVES: To compare the density of lymphatic vessels and VEGF-C and VEGF-D expression in Warthin's tumours (WTs) and oncocytic adenomas (OCAs). METHODS: Twenty three WTs and 13 OCAs of the parotid gland were analyzed. Lymphatic vessels were detected using the D2-40 antibody. For evaluation of the intratumour and peritumour lymphatic vessel density (iLVD and pLVD, respectively) the area of greatest vascularisation (hot spots) was chosen, using a ×40 field, and the number of vessels per square millimeter was counted in a ×200 field. The staining intensity for VEGF-C and VEGF-D immunoreaction in the tumour cells was graded from 0 to 3. RESULTS: The mean iLVD and pLVD values in WTs was 4.7 (range 1-8) and 6.9 (range 3-10), those in the OCAs 1.0 (range 0-3) and 5.8 (range 2-8), respectively. The differences in the iLVD, but not pLVD between the two tumour groups were statistically significant. In both entities, the pLVD markedly outnumbered the iLVD. The intratumour vessels in the WTs were present exclusively in the lymphoid stroma. In the group of 23 WTs, 13 (56.6%), 17 (73.9%) and 10 (43.4%) samples revealed positive VEGF-C, VEGF-D and both immunoreactions, respectively. 10 of 13 (77%) cases revealed VEGF-D immunoreaction and in none of them was the VEGF-C reaction present. CONCLUSION: The tumours had a comparable high density of peritumorous lymphatic network. However, WTs markedly differed from OCAs in the number of the intratumorous vessels. These were abundant solely in the stroma of WT, while practically lacking in the neoplastic epithelium of the WT and relatively rare in OCAs. We suggest that homeostasis in both entities is mediated mainly by peritumorous lymphatics. The lymphatic drainage in WTs is also fostered exclusively by stromal lymphatics, whereas in stroma poor OCAs by the vessels present in their neoplastic epithelium. We also believe that WTs stimulate proliferation of pre-existing lymphatic capillaries by means of the paracrine secretion of VEGF-C and VEGF-D in the neoplastic as well as reactive stromal cells, while in the OCAs only the latter factor takes part in their lymphangiogenesis.

Expression of VEGF-C/-D and lymphangiogenesis in salivary adenoid cystic carcinoma.

AIMS: Some human neoplasms stimulate lymphangiogenesis through the over-production of vascular endothelial growth factors C/D (VEGF-C/D). Previously little attention has been paid to the mechanisms of lymphogenous spread of salivary adenoid cystic carcinoma (SACC). The current study investigates the presence of lymphatic network and the role of VEGF-C and VEGF-D in its formation. METHODS: The retrospective study was performed in 20 (12 females and 8 males) patients diagnosed with SACC. For the evaluation of VEGF-C/D immunoreactivity, semiquantitative histoscore was calculated as a sum of positive tumor cell score (range 0-3) and staining intensity (range 0-3). Lymphatic vessel density (LVD) was determined as the number of D2-40 positive lymphatic capillaries present at "hot spots". Moreover, the values of histoscores were calculated in surrounding normal parotid parenchyma and compared to those counted in tumors. LVD in the tumor center (iLVD), in its periphery (pLVD), and in healthy gland were identified. RESULTS: VEGF-C/D expression, iLVD and pLVD were higher in SACC than in normal gland. The VEGF-C/D score correlated neither with pLVD nor with iLVD. High iLVD values were associated with poor survival. CONCLUSIONS: The authors present the first study demonstrating the existence of lymphatic vessels in SACC.

Secondary hypertension and hirsutism as a clinical manifestation of tumor duplicity.

BACKGROUND: The differential diagnosis of the pathogenetic causes of hirsutism in combination with hypertension is a challenge for clinicians. METHODS AND RESULTS: This case report demonstrates a patient suffering from two hormonally active tumors - an adrenal adenoma with primary aldosteronism and a Leydig cell ovarian tumor with hyperandrogenism. The task of the authors was easier due to the perimenopausal age of the proband. Adrenal selective venous sampling was very helpful in the diagnosis of these active endocrine tumors. Both were resolved by a single laparoscopic surgery. CONCLUSION: The combination of the two described tumors is a unique clinical finding. The resolution using laparoscopy in a single procedure provided an elegant and efficient therapeutic approach.

[Closed pleural biopsy in the diagnostics of malignant pleural involvement]. / Necílená biopsie pleury v diagnostice maligního pleurálního výpotku - nase zkusenosti za posledních 15 let.

INTRODUCTION: Pleural effusion is a frequent reason for a pulmonologist´s investigation. The cornerstone is to distinguish transudative pleural effusion from exudative pleural effusion. In the case of the exudative pleural effusion the next step is detection of malignant etiology of pleural effusion. We have a variety of any non-invasive or invasive examinations. The pleural biopsy is one of the most important methods for diagnostics of malignant pleural effusion. MATERIAL AND METHODS: Two hundred and twenty-two closed pleural biopsies (CPB) were performed in 208 patients with pleural effusion, where the cytologic examination of pleural fluid was negative. The authors evaluated the value of CPB for the diagnosis of malignant pleural involvement. RESULTS AND CONCLUSION: Total sensitivity, specificity, accuracy, positive predictive value and negative predictive value were 63.1%, 100%, 73.9%, 100% and 52.8%, but in the group of mesotheliomas these results were 59.1%, 100%, 79.4%, 100% and 70.7%. The incidence of complications and representative sampling of the pleura was mentioned. The authors compared the diagnostic value and the incidence of complications of various diagnostic methods in malignant pleural involvement by data in the literature.

Synchronous second primary neoplasms detected by initial staging F-18 FDG PET/CT examination in patients with non-Hodgkin lymphoma.

PURPOSE OF THE REPORT: Cases of synchronous non-Hodgkin lymphoma (NHL) and second primary carcinoma in previously untreated immunocompetent patients are relatively rare. The aim of this part of our prospective study was to a revealed 2-F-18 fluoro-2-deoxy-D-glucose (F-18 FDG) positron emission tomography (PET)-positive lesion in an extranodal organ suggestive of second primary neoplasm in newly diagnosed NHL patients. MATERIALS AND METHODS: A total of 209 patients with NHL underwent initial staging F-18 FDG PET/computed tomography (CT). The finding was assessed by a radiologist, nuclear medicine physician, and hematologist. In 6 suspicious cases (2.9%) of second neoplasm, the decision was made to perform further investigations before lymphoma therapy. RESULTS: Two patients were diagnosed with colorectal carcinoma, 1 with esophageal adenocarcinoma, 1 with invasive ductal breast carcinoma, 1 with medullary thyroid carcinoma, and 1 with squamous cell lung carcinoma. In 5 of the 6 patients, the second solid tumor was completely asymptomatic and revealed only by F-18 FDG PET/CT examination. CONCLUSIONS: We conclude that in patients with NHL, appropriate imaging, clinical, and histologic analysis of organ lesions detected by F-18 FDG PET/CT will occasionally demonstrate significant synchronous neoplasms.

Long-term outcome of patients with peripheral T-cell lymphoma treated with first-line intensive chemotherapy followed by autologous stem cell transplantation.

BACKGROUND: Peripheral T-cell lymphomas (PTCL) are infrequent subtypes of non-Hodgkin's lymphomas. The clinical course is aggressive and the median survival is about 2-3 years. An optimal first-line chemotherapy protocol has not been established and the role of high-dose therapy with autologous stem cell transplantation (ASCT) is still unclear. AIM: To analyze the long-term outcome of unselected PTCL patients treated with intensive first-line chemotherapy with high-dose therapy and ASCT. METHOD: Here we report our experience with 29 patients with PTCL. The histological subtypes were as follows: peripheral T-cell lymphoma, not otherwise specified n=13; anaplastic large cell lymphoma (ALCL) ALK-negative n=5; ALCL ALK-positive n=3; ALCL with an unknown ALK status n=3; angioimmunoblastic lymphoma n=1; hepatosplenic lymphoma n=1; Sézary syndrome n=1; and enteropathy-associated T-cell lymphoma n=2. The median age at diagnosis was 48 years (29-64), most patients had advanced Ann Arbor stages (22 patients, 77%), IPI score ≥3 was found in 13 (45%) and PIT score ≥2 in 17 (59%) of the 29 patients. Eighteen patients received first-line high-dose therapy and autologous SCT consolidation; two patients were consolidaed with allogeneic SCT in the 1st complete remission and one patient in the 1st relapse. Ten patients with FDG-avid lymphoma were examined with integrated Positron emission tomography/ Computed tomography (PET/CT) at the time of diagnosis and after first-line therapy, two other patients were assessed with Positron emission tomography/ Computed tomography (PET/CT) only at time of restaging. RESULTS: Nineteen (66%) patients achieved complete remission, 3 (10%) partial remission and 7 (24%) patients failed the treatment. The overall response rate was 76%. PET negativity (complete metabolic response) after therapy was achieved in 8/12 (75%) individuals. After a median follow-up of 55.1 months, 14 (48.3%) patients relapsed or progressed and nine patients died (lymphoma progression). Eleven patients (50% of chemosensitive patients) survived more than 50 months. Three of the long-term survivors were treated with allogeneic SCT. The 2-year event-free survival (EFS) was 52% (95% confidence interval [CI], 0.33-0.71); the 2-year overall survival (OS) rate reached 65% (95%CI, 0.47-0.84). PET negativity was associated with a lower probability of relapse (chi-square p=0.09). CONCLUSION: Our data show that intensive first-line therapy with etoposide-doxorubicine-based regimens and ASCT consolidation may lead to long-term disease control in about a half of patients with chemosensitive PTCL. Achievement PET negativity is probably an essential prerequisite for long-term complete remission.

Standardised uptake value of 18F-FDG on staging PET/CT in newly diagnosed patients with different subtypes of non-Hodgkin's lymphoma.

OBJECTIVES: Positron emission tomography using 2-[fluorine-18]-fluoro-2-deoxy-D-glucose ((18) F-FDG) is considered to be the most beneficial imaging method for staging patients with non-Hodgkin's lymphoma (NHL). The intensity of (18) F-FDG accumulation may be determined by calculating the so-called standardised uptake value (SUV). The study aimed at assessing the benefit of SUV(max) determination in staging (18) F-FDG PET/CT in untreated patients with NHL. METHODS: One hundred and forty-nine initial staging (18) F-FDG PET/CT scans performed in patients with NHL between January 2007 and August 2009 were assessed, and the SUV(max) was determined. RESULTS: The highest mean and median values of SUV(max) were observed in patients with diffuse large B-cell lymphoma (DLBCL), the lowest mean and median values were found in small lymphocytic lymphoma. The overlap in SUV(max) < 10 between DLBCL and the other subgroups of NHL was very significant. Statistically, no correlation was found between the lactate dehydrogenase and SUV(max) values. On the other hand, a correlation of the Ki-67 proliferative index of tumour cells and SUV(max) was revealed (r = 0.409, P < 0.001). The geometric mean of SUV(max) in patients with Ki-67 ≤ 60 and those with Ki-67 > 60 was 8.8 and 14.3, respectively (P < 0.001). CONCLUSIONS: The results confirm that SUV(max) is not beneficial for making a more precise diagnosis in most patients with NHL. Correlation of SUV(max) with the Ki-67 values suggests that SUV(max) might have a prognostic values in NHL.

Rituximab does not adversely affect the stem cell mobilization and engraftment after high-dose therapy and autologous transplantation in patients with diffuse large B-cell lymphoma in first complete or partial remission.

AIMS AND METHODS: The goal was to investigate the effect of prior combined rituximab (R) and intensive chemotherapy on peripheral blood stem cell mobilization and their engraftment after stem cell transplantation (ASCT) in 69 patients with poor-risk, diffuse large B-cell lymphoma (DLBCL). RESULTS: A statistically comparable median number of CD34+ stem cells was collected in both groups (13.80x10(6)/ kg in the non-R group and 7.81x10(6)/kg in the R group; p = 0.110). A trend toward greater number of CFU-GM was found in the non-R group (98.1x10(4)/kg) compared to the R group (76.6x10(4)/kg; p = 0.068). The non-R patients had a much higher median number of BFU-E (90.9x10(4)/kg) than the R patients (31.3x10(4)/kg; p = 0.001). CONCLUSIONS: Hematopoietic engraftment was rapid for both groups and no different between them. The 3-year event-free survival was 90.4 % in the R group and 67.2 % in the non-R group (p = 0.04), but there was no significant difference in the 3-year overall survival (94,7 % vs 83,5 %; p = 0.179).

Precursor T-lymphoblastic lymphoma as a secondary malignancy in a young patient after successful treatment of acute promyelocytic leukemia.

BACKGROUND: Acute promyelocytic leukemia (APL) is a relatively rare subtype of acute myeloid leukemia. It has become the best curable subtype of acute leukemias in adults due to the inclusion of all-trans-retinoic acid (ATRA) in the treatment. Despite the efficacy of ATRA, chemotherapy must be added in APL patients in order to maintain durable complete remission. However, chemotherapy administration is inevitably related to many complications, including the risk of secondary malignancies. T-lymphoblastic lymphoma (T-LBL) is an infrequent disease that belongs to the group of highly aggressive lymphomas. CASE REPORT: The authors describe the case of a 25-year-old woman who was treated for APL in 2002 and developed precursor T-LBL 5 years later. CONCLUSION: Several cases of secondary acute lymphoblastic leukemias in 'cured' APL patients have been described, but probably no patient with secondary precursor T-LBL. Secondary malignancy has become one of the topics discussed (not only) in APL patients. It is apparently related to the excellent treatment outcomes and long-term survival. Better tailored treatment based on relevant prognostic factors allowing chemotherapy reduction or omission in some patients is needed.

Prolonged survival of patients with peripheral T-cell lymphoma after first-line intensive sequential chemotherapy with autologous stem cell transplantation.

BACKGROUND: Nodal peripheral T-cell lymphomas (PTCLs) are infrequent subtypes of non-Hodgkin's lymphomas. The WHO classification recognizes three subgroups of nodal PTCL: peripheral T-cell lymphoma not otherwise specified (PTCL, NOS), anaplastic large cell lymphoma (ALCL) and angioimmunoblastic lymphoma (AIL). The clinical course is aggressive and despite multiagent chemotherapy, the median survival is about 2 years. Optimal first-line chemotherapy is not established and the role of high-dose therapy with autologous stem cell support is still controversial. AIM: To analyze the long-term outcome of PTCL patients treated with intensive first-line chemotherapy with highdose therapy and autologous transplant consolidation. METHOD: Sequential chemotherapy protocol consisting of 3 cycles of CHOEP-21-like regimen (PACEBO), 1 cycle of an ifosfamide and methotrexate-based regimen (IVAM) and a priming regimen with high-dose cytosine arabinoside (HAM). Consolidation was provided with myeloablative conditioning (BEAM 200) and autologous stem cell support. Eighty-four patients with aggressive high-risk lymphoma were treated with the sequential protocol from 2000 to 2007 in our institution. Here we report our experience with 18 patients with nodal PTCL (10 PTCL, NOS; 3 ALCL, ALKnegative; 2 ALCL, ALK-positive; 2 ALCL, unknown ALK status; 1 AIL). RESULTS: Eleven (61 %) patients achieved complete remission, 3 (17 %) partial remission and 4 (22 %) patients failed the procedure. The overall response rate was 77.8 %. After a median follow-up of 25.7 months, nine patients relapsed or progressed (6 PTCL, NOS; 2 ALCL ALK-positive; 1 ALCL ALK-negative; median 14.1 months) and four patients died (lymphoma progression). The relapse was treated with allogeneic stem transplantation in one patient. The 2-year progression-free survival (PFS) was 52 % (95 % CI, 0.27 to 0.76); the 2-year overall survival rate reached 71 % (95 % CI, 0.47 to 0.95). CONCLUSION: Our results show that intensive first-line chemotherapy with high-dose therapy and autologous transplant consolidation offers a chance for long-term survival in patients with chemosensitive PTCL.

The value of dynamic contrast enhanced breast MRI in mammographically detected BI-RADS 5 microcalcifications.

AIMS: To evaluate the role of dynamic contrast-enhanced magnetic resonance imaging (MRI) in the diagnosis of BI-RADS-5 type of microcalcifications of the breast, to compare the size of the microcalcification lesions using mammography (MG) and MRI, and to determine the value of MRI in surgery for microcalcifications. The study also determines the morphology of microcalcification lesions, assesses kinetic curves and compare MRI features of ductal carcinoma in situ (DCIS) for different histopathological grades. METHODS: Our group consisted of 32 patients with mammographically detected BI-RADS 5 microcalcifications. The MRI was done in this group of women which was later followed by stereotactic vaccum-assisted biopsy (SVAB). Surgery was performed on all patients with a biopsy that resulted in a diagnosis of breast cancer or atypical ductal hyperplasia (ADH). RESULTS: Of our group of 32 patients, there were 35 mammograhically detected microcalcification lesions, 32 DCIS, one ADH and two benign findings according to the final histology. The microcalcification lesions were larger using MRI than in MG in 10 women. We diagnosed DCIS multifocality in 6 women and bilateral carcinoma in one woman. As with kinetic curve assessment, we found in 67 % of DCIS a rapid rise, 27 % a moderate and in 6 % a slow initial rise. With the pattern of enhancement in the delayed phase, we found in 30 % of DCIS a washout pattern, 67 % a plateau and in 3 % a persistent pattern. Noted difference between high and low grade DCIS was confirmed. CONCLUSIONS: MRI sensitivity in the detection of DCIS was 94 % in our group of patients and was the sole evidence for detection of multifocality and bilateral incidence of carcinoma. In 26 % of women the outcome of MRI was the most important for converting breast conserving surgery to mastectomy.

Pseudoangiomatous stromal hyperplasia of breast: a case report.

AIM: To present a case of pseudoangiomatous stromal hyperplasia (PASH) and its findings under 1. mammography - MG, 2. ultrasonography - USG and 3. magnetic resonance imaging - MRI. MATERIALS AND METHODS: A woman 39 years of age with a history of mass in her right breast of 3 months duration was subjected to a routine examination of the mass using MG & USG. According to the modality findings a core cut biopsy was done following which the samples were send for histological analysis. Later, MRI was done as advocated by the surgeon to get a better picture of the extent of the lesion prior to surgery. RESULTS: Bilateral mammogram views revealed in the patient's right breast a huge well-bordered tumour of lobulated contour without halo sign. Sonography revealed a big well-demarcated tumour in the central part of the right breast which was cystic and lobulated in shape. Histological analysis of the sample confirmed pseudoangiomatous stromal hyperplasia (PASH). MRI under a breast array coil revealed a mass of 85 x 75 x 35mm in the right breast. Finally, based on the clinical, radiological and histological report the mass was diagnosed as benign and despite the massive size of the mass, tumour excision alone was done and not mastectomy. The right breast after the huge tumour excision was almost normal in size compared to the left. CONCLUSION: PASH should be included in the differential diagnosis of a circumscribed or partially circumscribed mass, especially in the pre-menopausal female population. These benign masses often grow over time and can recur locally. Radiological diagnosis of PASH is usually done by MG and USG followed by core cut biopsy for histological analysis. However great the mass is, excision only of the tumor mass is recommended and not mastectomy.

Cystic parathyroid adenoma within a multinodular goiter: a rare cause of primary hyperparathyroidism.

Parathyroid cysts are uncommon lesions that do not have a specific sonographic appearance. We report a rare case of a functionally active cystic parathyroid adenoma as a cause of primary hyperparathyroidism and discuss the difficulties associated with the diagnosis. In this case, the association with a multinodular goiter made preoperative differentiation from thyroid cysts difficult. Demonstration of a high intact parathyroid hormone level in the aspirated cyst fluid was critical for the correct diagnosis.

Relapsed follicular lymphoma sequentially treated with rituximab and 90Y-ibritumomab tiuxetan. Case report.

BACKGROUND: Monoclonal antibodies have dramatically changed the treatment possibilities for follicular lymphoma. (90)Y-ibritumomab tiuxetan (Zevalin) is the first radioimmunotherapy agent approved for the treatment of relapsed and resistant follicular lymphoma patients. Long-term benefit was observed especially for patients achieving CR after radioimmunotherapy. METHODS AND RESULTS: A 65-year-old female patient with the second relapse of CD20 positive follicular lymphoma and multiple concomitant diseases was treated with four weekly doses of rituximab (375 mg/m(2)). (18)F-fluoro-deoxyglucose positron emission tomography combined with computed tomography (PET-CT) demonstrated only partial response to therapy with persistent PET scan positivity in enlarged abdominal lymph nodes. Therefore, it was decided to treat her with a 1200-MBq (32-mCi) dose of (90)Y-ibritumomab tiuxetan radioimmunotherapy. No acute complications were noted afterwards. Hematological nadirs were reached 4 weeks later, with a platelet count of 24 x 10(9)/l that normalized within the next 2 weeks. The patient had neither infection nor bleeding complications. Eight weeks after radioimmunotherapy, the PET-CT scans documented only 3 lymph nodes around the abdominal aorta, maximum size 2 x 1 cm. The PET scan analysis proved no accumulation of (18)F-fluoro-deoxy-glucose in any lymph nodes or other organs and tissues. CONCLUSIONS: Sequential treatment with rituximab and (90)Y-ibritumomab tiuxetan may be an interesting alternative in cases of relapsed follicular or other indolent lymphomas in pretreated or older patients with other concomitant diseases.

T-cell gamma/delta hepatosplenic lymphoma - prolonged remission induced by aggressive first line treatment.

T-cell gamma/delta hepatosplenic lymphoma is a primary extranodal lymphoma, distinct from other T/LGL lymphomas. The clinical course is aggressive, and despite use of the multiagent chemotherapy and young age of the patients, the median survival is less than 1 year. Curability of this disease is still uncertain. We reported a case of the successful intensive treatment with splenectomy, chemotherapy a first line autologous stem cell transplant. High intensity cytarabine- platinum containing regimen (EDHAP) may overcome primary resistance to conventional alkylating agents.