Atypical pituitary adenomas: clinical characteristics and role of ki-67 and p53 in prognostic and therapeutic evaluation. A series of 50 patients.

The aim of the study was to assess incidence rate, hormonal activity, and local invasiveness and evaluate outcomes of so-diagnosed atypical pituitary adenomas that underwent endoscopic endonasal surgery at the Division of Neurosurgery of Università degli Studi di Napoli Federico II. According to the 2004 WHO classification, atypical pituitary adenomas are defined by an invasive growth, Ki-67/MIB-1 proliferative index greater than 3 %, high p53 immunoreactivity, and increased mitotic activity. A retrospective analysis of a series of 434 pituitary adenomas that underwent endoscopic endonasal surgery at our department between March 2007 and February 2013 was performed. Fifty adenomas (11.5 %) met the criteria of diagnosis of atypical lesions; 10 (21.6 %) of the 50 patients were recurrent tumors with a previous transsphenoidal surgery. Forty-one (82 %) were macroadenomas, and 21/50 (42 %) showed a clear invasion of the cavernous sinus. Histotype of atypical adenomas figured out to be nonfunctioning in 23 cases (46 %), PRL secreting in 10 cases (20 %), ACTH secreting and GH secreting each apart in 8 patients (16 %), and in a single case a GH/PRL secreting adenoma (2 %). The Ki-67 labeling index ranged from 3.5 to 22.5 % (mean 5.6 %). Tumor recurrence was observed in six cases (12 %) after a mean time of 18 months (range 9-24 months). Mean follow-up was 36.5 months (range 2-80 months). Atypical pituitary adenomas account for ca. 10 % of all pituitary adenomas; these lesions have peculiar features. It should be considered that a strong immunopositivity of p53 and higher Ki-67 LI could predict an increased risk of tumor recurrence, but more studies and larger series are expected to confirm and enlarge the diagnostic and therapeutic management process of these lesions.

Multidisciplinary diagnostic approach combining fine needle aspiration, core needle biopsy and imaging features of a presacral myelolipoma in a patient with concurrent breast cancer.

Myelolipomas are uncommon benign tumors composed of mature adipose tissue mixed with hematopoietic elements; these tumors can occur in both the adrenal glands and extra-adrenal locations, the presacral region being the most frequent extra-adrenal site. We present a case of presacral myelolipoma diagnosed by fine needle aspiration (FNA) and core needle biopsy (CNB) in a 55-year-old woman with concurrent invasive ductal breast cancer. TC and RM imaging were consistent with the diagnosis of presacral myelolipoma. The lesion was discovered incidentally during the staging procedure for breast malignancy. The purpose of our work is to describe the FNA and CNB finding in combination with the imaging features of this uncommon lesion.

Leiomyosarcoma of the thyroid gland: A case report and literature review.

Primary smooth muscle tumors of the thyroid gland are extremely rare neoplasms. Due to their rarity, clinical case studies concerning management are lacking. According to a literature review, only 19 cases of primary thyroid leiomyosarcomas (TLs) have been reported. In the majority of patients, the prognosis is poor since adjuvant radiochemotherapy is ineffective on local recurrence and on long-term survival. In this study, we report the case of a 77-year-old male affected by a rapidly enlarging mass of the anterior neck, associated with bilateral lung metastases, and increasing dysphagia and dyspnea during the previous 6 months. A Tir4 neoplasm fine needle cytological diagnosis of the right thyroid lobe was reached and the patient underwent total thyroidectomy (TT). Definitive histological examination identified a TL. The patient succumbed 40 days later due to respiratory distress. A literature review was performed and TL differential diagnoses, management, including alternative treatment strategies, and adjuvant therapy were analyzed. TL is an aggressive rare mesenchymal malignant tumor. Although an improved multimodal approach is often necessary, TT and neck dissection represent the treatment of choice and are often the only possible therapy. Adjuvant radiochemotherapy appears to be ineffective and a high mortality rate is observed. TL remains a fatal tumor, and innovative and more effective therapeutic strategies to improve management and outcomes are required.

Advanced-stage Hodgkin lymphoma: US/chest radiography for detection of relapse in patients in first complete remission--a randomized trial of routine surveillance imaging procedures.

PURPOSE: To compare the use of fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) with the use of a combination of ultrasonography (US) and chest radiography for systematic follow-up of patients with high-risk Hodgkin lymphoma. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. In a single center between January 2001 and December 2009, patients with advanced-stage Hodgkin lymphoma who had responded completely to first-line treatment were randomly assigned (1:1) to follow-up with either PET/CT or US/chest radiography. Follow-up included clinical and imaging procedures at 4, 8, 12, 16, 20, 24, 30, 36, 48, 60, 84, and 108 months after treatment discontinuation. When clinical and/or imaging results were positive, recurrence was confirmed histologically. The primary endpoint was to compare the sensitivity of the two follow-up imaging approaches. Secondary endpoints were their specificity, positive and negative predictive values, time to recurrence detection, radiation risks, and costs. RESULTS: A total of 300 patients were randomized into the two arms. The study was closed after a median follow-up time of 60 months, with a relapse rate of 27%. Sensitivity for detection of Hodgkin lymphoma was similar for the two follow-up approaches. All of the relapses (40 of 40) were identified with FDG PET/CT (100%) and 39 of 40 relapses were identified with US/chest radiography (97.5%; P = .0001 for the equivalence test). US/chest radiography showed significantly higher specificity and positive predictive value than did PET/CT (96% [106 of 110] vs 86% [95 of 110], respectively; P = .02; and 91% [39 of 43] vs 73% [40 of 55], respectively; P = .01). Exposure to ionizing radiation was estimated to be 14.5 mSv for one PET/CT examination versus 0.1 mSv for one chest radiographic examination. Estimated cost per relapse diagnosed with routine PET/CT was 10-fold higher compared with that diagnosed with routine US/chest radiography. CONCLUSION: US and chest radiography are diagnostic tools that enable effective, safe, and low-cost routine surveillance imaging for patients at high risk of Hodgkin lymphoma relapse.

Isolated mediastinal amyloidosis mimicking a neoplastic lesion.

Isolated mediastinal amyloidosis is a rare condition. We report an unusual case of amyloid presented as an isolated mass, entirely confined within anterior mediastinum and FDG-avid, mimicking a neoplastic lesion. Because the differential diagnosis included several diseases as lymphoma, a biopsy via mediastinotomy was attended to avoid unnecessary sternotomy. The pathological results diagnosed to be an amyloidosis. The patient was asymptomatic and biopsy allowed an exact diagnosis, thus we decided against the complete excision. No monoclonal gammopathy and/or amyloid deposition were found. Thus, other treatments as high-dose melphalan and/or autologous stem cell transplantation were not indicated.

Giant breast tumors in a patient with Beckwith-Wiedemann syndrome.

Beckwith-Wiedemann syndrome (BWS) is an overgrowth disorder with increased risk of embryonal tumors, such as Wilms tumor, hepatoblastoma, neuroblastoma, and rhabdomyosarcoma. We report on a patient with BWS that developed a giant fibroadenoma of the breast that was surgically removed. The tumor relapsed 8 months after the surgery and the patient underwent partial mastectomy. Although the patient presented several clinical features of BWS, a molecular diagnosis was not achieved despite extensive molecular investigations on both blood and tumor tissue. A SNP array revealed a de novo 7p22.1 loss in both blood and breast tumor involving the mismatch repair gene PMS2 gene that may be potentially associated with the breast tumor. In conclusion, it remains unclear whether BWS patients have an increased risk of breast lesions or a yet unknown molecular defect is responsible for the rare occurrence of this tumor in BWS.

Acinic cell carcinoma of the breast arising in microglandular adenosis.

Acinic cell carcinoma is a rare breast tumour belonging to salivary gland-like tumours of the breast. They are "triple-negative" breast cancers even if their biological behaviour seems to be more favourable. Herein we present an acinic cell carcinoma arising on a background of typical and atypical microglandular adenosis in a 58-year-old woman, along with a review of the literature.

Multifocal thoracic chordoma mimicking a paraganglioma.

Chordoma of thoracic vertebras is a very rare locally invasive neoplasm with low grade malignancy arising from embryonic notochordal remnants. Radical surgery remains the cornerstone of the treatment. We describe a case of multifocal T1-T2 chordoma, without bone and disc involvement, incidentally misdiagnosed as a paraganglioma, occurring in a 47-year-old male asymptomatic patient. Neoplasm was radically removed by an endocrine surgeon through a right extended cervicotomy. A preoperative reliable diagnosis of chordoma, as in the reported case, is often difficult. Radical surgery can provide a favorable outcome but, given the high rates of local recurrence of this neoplasm, a strict and careful follow-up is recommended. Although very rare, chordoma should be suggested in the differential diagnosis of the paravertebral cervical masses of unknown origin. Spine surgeon consultation and a FNB should be routinely included in the multidisciplinary preoperative work-up of these neoplasms.

Multicentric encapsulated papillary oncocytic neoplasm of the thyroid: A case diagnosed by a combined cytological, histological, immunohistochemical, and molecular approach.

Fine-needle aspiration (FNA) diagnosis of oncocytic lesions is challenging. In fact, oncocytic changes occur in inflammatory, hyperplastic, and neoplastic settings, including both benign and malignant tumors. The rare oncocytic variant of papillary thyroid carcinoma (PTC), shows papillae composed by cells with large oncocytic granular cytoplasm featuring clear PTC nuclear features. A morphological similar, but biologically distinct lesion, is the encapsulated papillary oncocytic neoplasia. Here, we first report on FNA, its cytological features together with histological, immunohistochemical, and molecular correlates.

Immunophenotyping analysis in invasive micropapillary carcinoma of the breast: role of CD24 and CD44 isoforms expression.

We analyzed immunohistochemically the expression of CD24 and spliced variants of CD44v5 and v9 in invasive micropapillary carcinoma (IMPC) of the breast that is a rather aggressive tumor characterized by alteration of cells adhesion molecules, early lymph node metastases and poor prognosis. We analyzed 31 high-grade IMPCs and compared their expression to 22 high grade (G3) invasive ductal carcinomas of the breast (IDCs). We found a higher expression of CD24 in high-grade IMPCs with a peculiar inverted apical localization, compared to IDCs, showing a strong cytoplasmic staining; normal breast tissue resulted completely negative. IMPCs showed reduced expression of CD44v5 and CD44v9 compared with IDCs, but without a statistical significant difference. This study demonstrated that IMPC represents a distinct entity of breast carcinoma with high expression of CD24 with a typical inverted apical membrane pattern and reduction of CD44 isoforms v5 and v9, compared to IDCs. These features could explain the high lymph-vascular invasion propensity and higher metastatic capability of these tumors and could be a useful tool for a future targeted therapy.

Cytological and histological detection of amyloid deposits in bone marrow of patients affected by multiple myeloma.

We recently published a study aiming to verify the frequency of amyloid deposits in the bone marrow of patients with multiple myeloma (MM) who did not present any signs or symptoms of systemic amyloidosis, applying the Congo red technique on bone marrow smears obtained by aspiration from the posterior iliac spine. The results suggested that nearly 40% of patients affected by MM may have amyloid deposits in their bone marrow. Subsequently, this finding has not been confirmed by another study performed with histological specimens of bone marrow in a similar clinical setting. To explain this discrepancy, we performed a comparative study on the bone marrows of 36 patients affected by MM, evaluated by both cytological and histological techniques. The results of this study confirm the high frequency of amyloid deposits in the bone marrow of patients affected by MM when the analysis is made on cytological smears, and indicate that the presence of amyloid on marrow smears is confirmed by core biopsies simultaneously performed in only 25% of cases. Should further studies confirm our findings, cytological assessment could be considered a sensitive technique to detect bone marrow amyloid deposits.

Efficacy and safety of rituximab treatment in patients with progressive transformation of germinal centers after Hodgkin lymphoma in complete remission post-induction chemotherapy and radiotherapy.

Because the lymphatic tissue of progressive transformation of germinal centers (PTGC) expresses CD20, rituximab treatment may prevent transformation to lymphoma of this rather atypical entity. We prospectively evaluated the efficacy of immunotherapy with rituximab (375 mg/m2 i.v. weekly for 4 consecutive weeks, followed by a single i.v. infusion of 375 mg/m2 every 3 months for 2 consecutive years) in 48 patients with biopsy-proven PTGC after Hodgkin lymphoma in complete remission post-induction therapy (4-6 courses of anthracycline-containing chemotherapy with radiotherapy). The event-free survival (EFS) of this series was compared with that of a historical cohort of 48 patients with PTGC developing after Hodgkin lymphoma in complete remission post-induction therapy, who underwent observation. At a median follow-up of 40 months, histology showed a malignancy in 27% of patients in the observation group (Hodgkin lymphoma, 13 patients) and in 2% of patients in the rituximab-protected group (non-Hodgkin lymphoma, one patient) (p ∼ 0.001). Rituximab was well tolerated in all treated patients. All relapses in the group not protected by immunotherapy involved the PTGC regions and non-contiguous nodal sites, which suggests that PTGC is a reservoir for malignant transformation and dissemination. The number needed to treat with rituximab to avoid one Hodgkin lymphoma relapse was four. Our study shows that prophylaxis with rituximab helps improve EFS in patients with PTGC and a history of Hodgkin lymphoma.

Lichen planus pigmentosus-like ashy dermatosis.

Ashy dermatosis, also known as erythema dyschromicum perstans, is an idiopathic dermal melanosis of unknown etiology. We here describe an unusual case of 63-year-old Caucasian male with ashy dermatosis and skin lesion of lichen pigmentosus-like. No treatment was tried because the lesions were totally asymptomatic. After a control, three months later, all lesions had cleared up. This case is of interest because it proves the existence of ashy dermatosis with clinical aspect lichen planus pigmentosus-like. This is the first case in the literature of lichen planus pigmentosus-like ashy dermatosis confirming the view that ashy dermatosis is a variant of lichen planus without the typically band-like infiltrate and Max Joseph spaces.

Nodal and extranodal soft tissue polymorphous hemangioendothelioma: a case report and review of the literature.

BACKGROUND: Polymorphous hemangioendothelioma is a rare vascular tumor of borderline malignant potential and only 10 cases have been described in the literature so far. METHODS AND RESULTS: We report a case of nodal and extranodal polymorphous hemangioendothelioma and review the literature. A 66-year-old man with an unremarkable past medical history was admitted for a left submandibular mass. The main nodule was composed of angiosarcoma-like areas mixed with angiomatous features; some vascular spaces with hobnail endothelium were seen. The tumor involved two adjacent lymph nodes. Immunohistochemically, the neoplastic cells were strongly positive for CD31 and vimentin. After a few months the tumor recurred and the patient was treated with radiation therapy. CONCLUSIONS: Polymorphous hemangioendothelioma is a distinct entity in the hemangioendothelioma group with its own clinical and histological features.

Analysis of Cox-2 expression in Wilms' tumor.

Cylooxygenase-2 (Cox-2) inhibitors have increasingly become therapeutic alternatives in some Cox-2-overexpressing neoplasms. As the treatment eligibility for these drugs hinges on Cox-2 expression, Cox-2 immunostaining has recently been widely examined in several malignant neoplasms. However, data on the expression of Cox-2 in Wilms' tumor (WT) are limited. In this study, we examined Cox-2 expression in 40 examples of WT to identify the prognostic impact, to evaluate the effects on tumorigenesis, and to answer the question of whether neoplasms with Cox-2 expression could benefit from treatment with specific Cox-2 inhibitors. Sections from paraffin-embedded tumor samples were immunostained by a standard ABC technique using Cox-2 mouse monoclonal antibody. As in other rare examples reported in the literature, Cox-2 immunoreactivity was analyzed and correlated with histological features and the staging of neoplasms. However, in contrast to other studies, we also evaluated the relation of Cox-2 positivity to age, sex, and survival of patients. The results of this study demonstrated that Cox-2 was ubiquitously expressed in all cases of WT and their neovasculature, independently of the type of neoplasm (tumors with a favorable or unfavorable histology), tissues which constitute the neoplasm (blastemal, mesenchymal and epithelial, heterologous or non-heterologous elements), patient age, sex, or stage of development and survival rate. Thus, Cox-2 inhibitors could be used for treating all cases of WT. Further studies, including molecular investigations, would be useful to confirm our hypotheses.