Criteria For Malignancy Research Articles

The Performance of Radiographic Criteria for Bone Malignancy When Applied to Computed Tomography and Magnetic Resonance Imaging

BackgroundThe conventional radiologic features that differentiate benign from malignant bone lesions were originally described using radiography (x-ray [XR]). When evaluating sectional imaging studies such as magnetic resonance imaging (MRI) and computed tomography (CT), one may apply these principles to identify malignant bone lesions. The aim of this study was to evaluate the performances of these radiographic features for detecting malignity when applied to CT and MRI. Materials and MethodsThis retrospective study was approved by our institutional ethical board. Thirty-nine patients with histopathologic proof of a high-grade bone malignancy and preoperative imaging data obtained with a minimum of two different modalities were included in the study. Four radiologists reviewed the images and scored the lesions for distinctness of margins, presence and type of periosteal reaction, matrix mineralization, and presence of soft tissue mass. The average score for each modality was then tested for accuracy with regard to the histopathology. ResultsWhen lesion margins were considered, XR was the best modality to detect a high-grade malignancy. MRI, especially postcontrast T1-weighted sequence, was the least helpful in this regard. There was no significant difference between CT and XR and between CT and MRI. When the periosteal reaction was considered, XR was the best modality to detect the malignant type of periosteal reaction. In this regard, MRI and CT were misleading; either by not detecting or undergrading periosteal reaction. MRI was the best modality to detect soft tissue mass. ConclusionConventional imaging criteria for bone malignancy can be misleading when applied to MRI or CT. When cross-sectional imaging features contradict those from XR, the latter should be the guide for clinical management.

Diagnosis and Therapy of Iris Lesions

The most common iris lesions are iris nevi, iris melanomas and iris pigment epithelium cysts. However, there is an abundance of rare differential diagnoses that have to be considered, including other melanocytic and non-melanocytic lesions. Diagnostic tools include the slit lamp examination, gonioscopy, tonometry, transillumination, ultrasound biomicroscopy (UBM), optical coherence tomography, fluorescein angiography and standardized photography-assisted documentation. The timely identification of malignant lesions (i.e. iris melanoma) is paramount. To assess malignancy criteria of iris nevi, the ABCDEF rule (age young, blood, clock hour inferior, diffuse growth, ektropion uveae, feathery margins) can be applied. Statistically, up to 11% of iris nevi may develop into iris melanomas within 20 years. TNM Staging follows the 2010 AJCC cancer staging manual and helps determine the optimal treatment strategy. Treatment options include radiotherapy, such as plaque brachytherapy and proton beam radiation therapy, as well as surgical excision. Both the surgical and the radiotherapeutic approaches show comparable local tumor control rates. However, the spectrum of therapy-related side effects and complications may differ amongst treatment modalities. After initial treatment, patients should be followed up every 3 - 6 months. Tumor-related mortality ranges between 0 - 11% and is significantly lower than in other uveal melanomas. A prognostic value of common genetic alterations, which have been identified as significant prognostic factors in posterior uveal melanoma, could not be shown for iris melanoma.

Lacrimal myoepithelial carcinoma ex recurrent pleomorphic adenoma: A clinicopathological report and review of the literature.

Myoepithelial carcinoma is an uncommon malignant tumor of the lacrimal gland, composed of neoplastic myoepithelial cells with an infiltrative growth. The present study describes a unique case of progressive proptosis and blindness of the right eye in a 68-year-old woman following total tumor removal for lacrimal pleomorphic adenoma. Clinical study, surgical exploration, and pathology revealed lacrimal myoepithelial carcinoma ex recurrent pleomorphic adenoma, T2N0M0. In addition, 18 cases of lacrimal myoepithelial tumor that have been previously described in the literature are reviewed. The application of clinical, radiological, histopathologic, and immunohistochemical investigations may help to reach the definite diagnosis. Criteria for malignancy of lacrimal myoepithelial tumor should be the same as salivary myoepithelial tumor diagnosis, until long-term outcome data for a larger number of patients with lacrimal myoepithelial carcinoma become available.

Diagnostik und Therapie von Irisläsionen

ZusammenfassungTeil des klinisch-ophthalmologischen Alltags ist die korrekte Diagnose tumoröser Irisläsionen. Insbesondere die Differenzialdiagnose und die Bewertung der Dignität anhand der Morphologie gestalten sich dabei oft schwierig. Dieser Beitrag gibt einen Überblick über das breite Spektrum von Iristumoren einschließlich empfohlener Diagnostik- und Therapiemodalitäten.

Synchronous malignant neoplasm in the oral cavity - case report

Approximately 555,000 new cases of head and neck cancer (HNC) are diagnosed annually worldwide. Moreover, second primary malignancy (SPM) occurs more commonly in the head and neck than in any other body region. A 67-year-old female patient was admitted to our Department for removal of an upper lip tumor. The patient underwent excision of the lip tumor under general anesthesia. Postoperative histopathology revealed a polymorphic, low-grade adenocarcinoma. Three weeks later, the patient was re-admitted to extend the margin of excision and perform lymphadenectomy. On physical examination, a second primary synchronous lesion was found on the left side of the hard palate. Lymphoscintigraphy was performed to determine the lymph node field and the sentinel lymph node. On ultrasonography, the lymph nodes were not enlarged. Extended excision of the upper lip was performed, and a 5-mm, hard palate tumor was removed with a margin of unchanged tissue. The patient was scheduled for adjuvant treatment. The criteria for a synchronous malignancy are as follows: both tumors must be malignant on histopathology, there must be a distance of at least 2 cm of unchanged mucosa between the index tumor and the primary tumor, the possibility that the second tumor is the metastasis of the index tumor needs to be excluded. In our patient, all these criteria were met. A thorough workup should include medical history, physical evaluation, and imaging, and it should be carried out on every step of treatment and during long-term follow-up in patients after cancer treatment. This is crucial, because not only is there a possibility of recurrence or metastases, but also a considerable percentage of patients may have a second primary lesion.

Systematic histopathological analysis of different 5-aminolevulinic acid-induced fluorescence levels in newly diagnosed glioblastomas.

OBJECTIVE Glioblastoma (GBM) is characterized by distinct intratumoral histopathological heterogeneity with regard to variable tumor morphology, cell proliferation, and microvascularity. Maximum resection of a GBM results in an improved prognosis and thus represents the aim of surgery in the majority of cases. Fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) is currently widely applied for improved intraoperative tumor visualization in patients with a GBM. Three intratumoral fluorescence levels (i.e., strong, vague, or no fluorescence) can usually be distinguished during surgery. So far, however, their exact histopathological correlates and their surgical relevance have not been clarified sufficiently. Thus, the aim of this study was to systematically analyze tissue samples from newly diagnosed GBMs with different fluorescence levels according to relevant histopathological parameters. METHODS This prospective study recruited patients who underwent 5-ALA fluorescence-guided resection of a newly diagnosed radiologically suspected GBM. Each patient received 5-ALA approximately 3 hours before surgery, and a modified neurosurgical microscope was applied for intraoperative visualization of 5-ALA-induced fluorescence. During surgery, tissue samples with strong, vague, or no fluorescence were collected. For each sample, the presence of tumor tissue, quality of tissue (compact, infiltrative, or no tumor), histopathological criteria of malignancy (cell density, nuclear pleomorphism, mitotic activity, and presence of microvascular proliferation/necrosis), proliferation rate (MIB-1 labeling index [LI]), and microvessel density (using CD34 staining) were investigated. RESULTS Altogether, 77 patients with a newly diagnosed, histopathologically confirmed GBM were included, and 131 samples with strong fluorescence, 69 samples with vague fluorescence, and 67 samples with no fluorescence were collected. Tumor tissue was detected in all 131 (100%) of the samples with strong fluorescence and in 65 (94%) of the 69 samples with vague fluorescence. However, mostly infiltrative tumor tissue was still found in 33 (49%) of 67 samples despite their lack of fluorescence. Strong fluorescence corresponded to compact tumors in 109 (83%) of 131 samples, whereas vague fluorescence was consistent with infiltrative tumors in 44 (64%) of 69 samples. In terms of the histopathological criteria of malignancy, a significant positive correlation of all analyzed parameters comprising cell density, nuclear pleomorphism, mitotic activity, microvascular proliferation, and necrosis with the 3 fluorescence levels was observed (p < 0.001). Furthermore, the proliferation rate significantly and positively correlated with strong (MIB-1 LI 28.3%), vague (MIB-1 LI 16.7%), and no (MIB-1 LI 8.8%) fluorescence (p < 0.001). Last, a significantly higher microvessel density was detected in samples with strong fluorescence (CD34 125.5 vessels/0.25 mm2) than in those with vague (CD34 82.8 vessels/0.25 mm2) or no (CD34 68.6 vessels/0.25 mm2) fluorescence (p < 0.001). CONCLUSIONS Strong and vague 5-ALA-induced fluorescence enables visualization of intratumoral areas with specific histopathological features and thus supports neurosurgeons in improving the extent of resection in patients with a newly diagnosed GBM. Despite the lack of fluorescence, tumor tissue was still observed in approximately half of the cases. To overcome this current limitation, the promising approach of complementary spectroscopic measurement of fluorescence should be investigated further.

MRI in the Assessment of BI-RADS® 4 lesions

The American College of Radiology (ACR) Breast Imaging-Reporting and Data System (BI-RADS) lexicon, which is used ubiquitously to standardize reporting of breast magnetic resonance imaging (MRI), provides 7 BI-RADS assessment categories to indicate the level of suspicion of malignancy and guide further management. A BI-RADS category 4 assessment is assigned when an imaging abnormality does not fulfill the typical criteria for malignancy, but is suspicious enough to warrant a recommendation for biopsy. The BI-RADS category 4 assessment covers a wide range of probability of malignancy, from >2 to <95%. MRI is an essential noninvasive technique in breast imaging and the role of MRI in the assessment of ACR BI-RADS 4 lesions is manifold. In lesions classified as suspicious on imaging with mammography, digital breast tomosynthesis, and sonography, MRI can aid in the noninvasive differentiation of benign and malignant lesions and obviate unnecessary breast biopsies. When the suspicion of cancer is confirmed with MRI, concurrent staging of disease for treatment planning can be accomplished. This article will provide a comprehensive overview of the role of breast MRI in the assessment of ACR BI-RADS 4 lesions. In addition, we will discuss strategies to decrease false positives and avoid false negative results when reporting MRI of the breast.

A modified reporting approach for thyroid FNA in the NIFTP era: A 1-year institutional experience.

The reclassification of noninvasive follicular variant of papillary thyroid carcinoma as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) has created diagnostic and management issues for thyroid fine-needle aspiration (FNA). In response to these challenges, the authors' laboratory adopted a NIFTP policy including 1) stringent criteria (requiring pseudo-inclusions, papillae, and/or psammoma bodies) for a malignant diagnosis of papillary carcinoma to limit false-positive results due to NIFTP and 2) the use of explanatory notes in cases with cytomorphologic features suggestive of possible NIFTP to encourage lobectomy over thyroidectomy. This study examined the effects of this policy on FNA classification and subsequent surgical management. All thyroid FNAs performed at Brigham and Women's Hospital (n = 1300) during a 1-year period were evaluated for changes in the use of diagnostic categories, explanatory NIFTP notes, and surgical follow-up in comparison with historical controls. The use of specific Bethesda categories did not significantly change. Only a single case of NIFTP was mistakenly classified as malignant. NIFTP was seldom suspected prospectively (17 of 1300; 1.3%); when NIFTP was suspected, cases were reported as suspicious for a follicular neoplasm/follicular neoplasm (n = 10) or suspicious for malignancy (SUS; n = 7). Five of the 7 SUS cases (71%) underwent partial thyroidectomy, compared to 19% of those classified as SUS without an explanatory NIFTP note (P < .02). Thyroid FNA reporting modifications due to NIFTP affect only a small subset of specimens. When NIFTP is suspected, an explanatory note promotes limited surgical excision. More stringent criteria for malignancy affect few cases while potentially limiting false-positive diagnosis due to NIFTP. Cancer Cytopathol 2017;125:854-64. © 2017 American Cancer Society.

Are actinic keratoses really squamous cell cancer? How do we know if they would become malignant?

Actinic keratosis (AK) is a very common skin disease caused by chronic sun exposure. AKs have historically been characterized as being “precancerous” or “premalignant.” It is true that these lesions do not possess metastatic potential, because they are confined to the epidermis, but it is not accurate to deem them “premalignant.” AK qualifies as a malignant neoplasm, because it also fulfills criteria for malignancy in classic pathology, namely, the capability, or potential, to kill by either destruction of tissue locally or by metastasis widely. In this context, AK is considered now by many a carcinoma in situ and can persist or progress to invasive squamous cell carcinoma (iSCC), which rarely metastasizes. Through this controversy, which speaks to an issue we have been debating for at least a century, we should like to start a constructive debate to reach a unanimous conclusion considering the various theories and points of view in the literature.

Expression of Contactin 4 Is Associated With Malignant Behavior in Pheochromocytomas and Paragangliomas.

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine, usually benign, tumors. Currently, the only reliable criterion of malignancy is the presence of metastases. The aim of this study was to identify genes associated with malignancy in PPGLs. Transcriptomic profiling was performed on 40 benign and 11 malignant PPGLs. Genes showing a significantly different expression between benign and malignant PPGLs with a ratio ≥4 were confirmed and tested in an independent series by quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemistry was performed for the validated genes on 109 benign and 32 malignant PPGLs. Functional assays were performed with hPheo1 cells. This study was conducted at the Department of Pathology of the Erasmus MC University Medical Center Rotterdam Human Molecular Genetics laboratory of the de Duve Institute, University of Louvain. PPGL samples from 179 patients, diagnosed between 1972 and 2015, were included. Associations between gene expression and malignancy were tested using supervised clustering approaches. Ten differentially expressed genes were selected based on messenger RNA (mRNA) expression array data. Contactin 4 (CNTN4) was overexpressed in malignant vs benign tumors [4.62-fold; false discovery rate (FDR), 0.001]. Overexpression at the mRNA level was confirmed using qRT-PCR (2.90-fold, P = 0.02; validation set: 4.26-fold, P = 0.005). Consistent findings were obtained in The Cancer Genome Atlas cohort (2.7-fold; FDR, 0.02). CNTN4 protein was more frequently expressed in malignant than in benign PPGLs by immunohistochemistry (58% vs 17%; P = 0.002). Survival after 7 days of culture under starvation conditions was significantly enhanced in hPheo1 cells transfected with CNTN4 complementary DNA. CNTN4 expression is consistently associated with malignant behavior in PPGLs.

Minimal (Limited) Pseudohyperplastic Prostatic Adenocarcinoma in Needle Prostatic Biopsy.

Study of minimum adenocarcinoma has been done almost exclusively on conventional acinar adenocarcinoma. Pseudohyperplastic adenocarcinoma can be confused with benign lesions because of its well-differentiated appearance and has not been studied when the biopsy shows few malignant glands (limited carcinoma). We reviewed 94 pseudohyperplastic adenocarcinomas diagnosed in prostatic biopsies for a period of 12 years and selected those measuring less than 1 mm or involving less than 5% of the biopsied tissue. We also reviewed 200 consecutive consultations. Four (4.2%) of the 94 cases were limited pseudohyperplastic adenocarcinomas, and 3 were from consultations. Three of them were mistaken for hyperplastic nodules, prostatic adenosis, or prostatic intraepithelial neoplasm. The number of glands varied between 6 and 50 (average 23). Three nodular histological patterns were identified-nodular, adenosis-like, and pseudohyperplastic carcinoma resembling prostatic intraepithelial neoplasia. The diagnosis of adenocarcinoma was not related to the number of neoplastic glands. Histological criteria that were useful included: crowded medium to large glands, papillary infoldings, branching glands, straight luminal borders, hyperchromatic nuclei, nucleomegaly, and apparent nucleoli. Areas of transition to conventional acinar adenocarcinoma were useful in recognizing four of these neoplasms, but were barely apparent in 2 of them. Hyperchromatic nuclei were found in all cases, whereas apparent nucleoli and nucleomegaly were only present in 4. The architectural and cytological criteria for limited acinar adenocarcinoma are only partially useful in interpreting minimum pseudohyperplastic adenocarcinomas. Knowledge of the criteria for malignancy in both neoplasms is important in order to avoid underdiagnosis of malignancy.

Endocrine Tumors—Part 1

FigureFigureSince the third volume of the World Health Organization (WHO) Classification of Tumours of Endocrine Organs was published in 2004, more than a decade ago, the following remarkable accomplishments have been achieved and included in the new fourth volume released in June of 2017. biologic behavior and prognosis new therapies and corresponding surrogate biomarkers immunophenotypes and molecular pathology genetic background of the tumors The new WHO volumes contain the following chapters: Tumors of the Pituitary Tumors of the Thyroid Gland Tumors of the Parathyroid Gland Tumors of the Adrenal Cortex Tumors of the Adrenal Medulla and Extra-adrenal Paraganglia Neoplasms of the Neuroendocrine Pancreas Inherited Tumor Syndromes In order to make new fourth WHO classification practically familiar among surgical pathologists and other professionals dealing with endocrine tumors, AJSP-RR is publishing 2 issues devoted to the fourth WHO classification of the endocrine tumors. Each chapter in WHO blue book has the structure with the items in order: Definition, Synonyms, Epidemiology, Etiology, Localization, Clinical Features (including diagnostic tests, Imaging), Macroscopy, Microscopy, Genetic Profile, Genetic Susceptibility, Prognosis, and Predictive Factors. This first AJSP-RR issue includes reviews on the following topics: (1) pituitary (Osamura), (2) medullary thyroid carcinoma (DeLellis), (3) nonmedullary thyroid cancers (Lam), and (4) adrenal cortex (Sasano). We have also included a case report devoted to cytopathology of paragangliomas. PITUITARY GLAND The fourth edition devotes attention to the transcription factors, which are involved in the differentiation pathways linked to particular hormone production; it has been shown that pituitary adenomas are derived from the differentiated anterior pituitary cells: somatotroph, lactotroph, thyrotroph, and so on. Therefore, the nomenclature of adenomas has been changed to somatotroph adenoma, lactotroph adenoma, thyrotroph adenoma, and others. The atypical adenoma category proposed in 2004 (Ki-67 >3% and p53 positive) is no longer included in the new WHO classification because its incidence is low and its significance for prognosis is not evident. Instead, the fourth edition proposes to use morphologic features that portend aggressive behavior, for example, sparsely granulated somatotroph adenoma with fibrous bodies, Crooke’s adenoma, and others. SSTR2, SSTR5, MGMT, and MSH6 are the predictive biomarkers that can be detected by immunohistochemistry. Familial tumor syndromes include 10 genetic alterations, and growth hormone (GH), prolactin (PRL) production in these conditions has been emphasized. THYROID Epithelial tumors: The most important achievement in the area of thyroid pathology is molecular genetics characterization of well-differentiated, follicular-patterned thyroid tumors composed of follicular cells with a differential diagnosis of papillary versus follicular and benign versus malignant. Several new categories have been introduced for papillary thyroid carcinoma. Several categories remained in the intermediate group between follicular adenoma versus follicular carcinoma/follicular variant of papillary carcinoma. These tumors sometimes are designated as “tumors of uncertain malignancy” and are still under discussion. “Noninvasive follicular thyroid neoplasm with papillary-like nuclear features” was adopted as a new terminology for the indolent tumors with particular nuclear appearance. Poorly differentiated carcinoma and oncocytoma were recognized as distinct entities. Medullary thyroid carcinoma is a unique tumor that produces calcitonin and carcinoembryonic antigen and is a part of multiple endocrine neoplasia type 2 syndrome. In the fourth edition, morphologic appearance is emphasized along with notable variants. Genetic molecular aberrations including RET and RAS are included in the discussion. ADRENAL CORTEX This review includes the Weiss criteria for malignancy in adrenal cortical tumors and Weiss and Lin-Weiss-Bisceglia criteria of malignancy in oncocytic adrenal cortical neoplasms. It is noteworthy to mention that various molecular parameters can distinguish adenomas from carcinomas. Carcinomas can be further divided into good and poor prognostic groups. Various hereditary syndromes are also included in this review. IN THE SECOND INSTALLMENT OF THIS ISSUE The second installment of the endocrine topics will contain review articles reflecting the WHO 2017 positions on the following: tumors of the adrenal medulla and extra-adrenal paraganglia, neuroendocrine tumors of the pancreas and inherited endocrine tumor syndromes.

Analysis of Efficacy and Tolerability of Bruton Tyrosine Kinase Inhibitor Ibrutinib in Various B-cell Malignancies in the General Community: ASingle-center Experience.

Ibrutinib, an irreversible inhibitor of Bruton tyrosine kinase (BTK), is a novel drug that has shown significant efficacy and survival benefit for treatment of various B-cell malignancies. The primary objective of the present study was to investigate the efficacy of ibrutinib therapy in various B-cell malignancies in the general community. The secondary objectives included studying the adverse effects, ibrutinib-induced peripheral lymphocytosis, and effect on immunoglobulin levels. The present study was a retrospective observational cohort analysis conducted at Abington Jefferson Health. The clinical response was determined from the hematologist's assessment and evaluated independently using the response criteria for each B-cell malignancy. Adverse effects were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. The Wilcoxon signed-rank test was used to compare immunoglobulin levels before and after ibrutinib. Forty five patients with B-cell malignancies and receiving ibrutinib therapy were eligible. The median age was 73 years (range, 49-96 years), and 84.4% of the patients had received≥ 1 previous therapy. The best overall response rate of all cohorts combined was 63.8%. The greatest overall response rate was observed in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (76.1%), followed by those with Waldenström macroglobulinemia (75%). Of the 45 patients, 88.9% experienced adverse effects. Antiplatelet activity of ibrutinib was most commonly observed (30.5%). Of note, 5 patients (11%) developed new-onset atrial fibrillation after drug initiation. Peripheral lymphocytosis after drug initiation was observed in most patients, with a peak level at 1 month (median lymphocyte count, 2.7× 103 cells/μL). Although the IgG levels at 3, 6, and 12 months had decreased (P= .01 for all) compared with the levels before ibrutinib, the IgA levels had not increased at 3, 6, 12, and 24 months (P= .6, P= .5, P= .3, and P= .9, respectively). Ibrutinib is a highly effective and tolerable drug for B-cell malignancies in the general community. In contrast to the previously reported rate of 5% to 7%, we observed a higher rate (11%) of atrial fibrillation, which might have resulted from the smaller sample size in the present study and the multiple comorbidities. Nonetheless, this treatment-limiting side effect requires further elucidation. Paradoxical lymphocytosis at the outset of therapy was a common and benign finding. In conjunction with the reported trials, the IgG levels decreased in the first year of continued therapy. However, the IgA levels did not increase, even after 2 years of therapy.

CORR Insights®: Pathologically Benign Lymph Nodes Can Mimic Malignancy on Imaging in Patients With Angiomatoid Fibrous Histiocytoma.

CORR Insights®: Pathologically Benign Lymph Nodes Can Mimic Malignancy on Imaging in Patients With Angiomatoid Fibrous Histiocytoma.

이하선에 발생한 악성 고립성 섬유종 1예

Solitary fibrous tumor is an uncommon spindle cell mesenchymal neoplasm with unpredictable behavior, usually arising in the pleura of the thoracic cavity. It is rarely found in the head and neck, and malignant solitary fibrous tumor is even rare. Malignant criteria of solitary fibrous tumor includes increased cellularity, increased mitoses (&gt;4 mitoses/10HPF), cytologic atypia, tumor necrosis and/or infiltrative margin. The treatment of malignant solitary fibrous tumor is complete surgical excision and adjuvant radiotherapy. We report a case of malignant solitary fibrous tumor originating from the parotid gland, relapsed very quickly and grown very rapidly in 6 weeks after surgical resection. (J Clinical Otolaryngol 2017;28-:104-109)

Autologous stem cell transplantation as a treatment modality for type 1 cryoglobulinemia in monoclonal gammopathy of renal significance.

e19500 Background: Type I cryoglobulinemia (CRYO) can be driven by disorders such as plasma cell dyscrasias. Monoclonal gammopathy of renal significance (MGRS) represents a group of kidney disorders characterized by the presence of a paraprotein; though not fitting the criteria for a hematologic malignancy. There exists no standard approach to manage these patients. Our patient is a 56-year-old man who was initially evaluated for edema. Workup revealed worsening renal function and proteinuria (Figure 1). Renal biopsy revealed abundant cryofibrinogen deposits and cryoglobulinemic glomerulonephritis with membranoproliferative pattern. Bloodwork showed type I (IgG Kappa) CRYO. Bone marrow evaluation revealed 7% clonal plasma cells. Further evaluation did not confirm a diagnosis of myeloma. Methods: Treatment was initiated with bortezomib, cyclophosphamide and dexamethasone. After 3 cycles of therapy the patient had normalization of his creatinine and marked improvement in edema. Peripheral blood stem cells were mobilized following the administration of high-dose cyclophosphamide (2gm/m2) plus filgrastim. He was subsequently conditioned for transplantation with high-dose melphalan (200mg/m2; HDM) followed by autologous stem cell rescue. He tolerated the procedure well without any unexpected toxicities; achieving prompt hematologic recovery Results: Evaluations post transplant revealed resolution of any circulating cryoglobulins and reduction in proteinuria. At 1 year post transplant, the patient has returned to his premorbid condition. Conclusions: Type 1 CRYO associated MGRS represents a complicated disorder for which there is no consensus treatment approach. As this process may be driven by clonal plasma cells, classical anti-myeloma therapy may provide a strategy for management. Given the typical low plasma cell burden in these patients, HDM has the potential to offer deep and durable remissions. Prospective studies are needed to validate this approach. [Table: see text]

Early detection of an atypical presentation of neuroleptic malignant syndrome: A case report.

Neuroleptic malignant syndrome (NMS), which is considered a neurologic emergency, is believed to be caused by exposure to dopamine antagonist or withdrawal from a dopamine agonist. This article reports a case of suspected atypical NMS in a patient following rapid conversion of ziprasidone to risperidone without titration. While the initial presentation did not fully meet the Diagnostic and Statistical Manual of Mental Disorders, 5th edition, diagnostic features, a sequential treatment strategy was initiated and the patient appropriately responded to antipsychotic cessation in addition to combination therapy with dantrolene and bromocriptine. Neuroleptic malignant syndrome diagnostic criteria, treatment, and prognosis are discussed.

Association between ultrasonographic appearance of splenic parenchyma and cytology in cats.

Objectives The purpose of this study was to determine whether the presence of a splenic mass or a diffusely moth-eaten parenchyma on ultrasonographic scans could represent potential criteria of malignancy in the feline spleen. Methods Feline patients with ultrasonographic images and cytological analysis of the spleen obtained by fine-needle aspiration were retrospectively included in a multicentre study. Results One hundred and ninety-five cats met our inclusion criteria. There was a lack of agreement between the moth-eaten ultrasonographic appearance of the spleen and the presence of a malignant neoplasia on cytological analysis. The sensitivity and specificity of a moth-eaten parenchyma for predicting malignant neoplastic disease were 13.2% and 84.8%, respectively. The sensitivity and specificity of a splenic mass >1 cm for predicting malignant neoplastic disease were 21.0% and 94.7%, respectively. A marbled appearance of the splenic parenchyma was significantly more frequent among patients examined with a high-frequency transducer (11-18 MHz) than among those examined with a low-frequency transducer (6.6-10 MHz) (27.6% vs 11.1%, respectively; P = 0.004). Similarly, although not statistically significant, a moth-eaten parenchyma was more frequent in the high-frequency transducer group than in the low-frequency group (17.1% vs 8.9%, respectively; P = 0.09). Conclusions and relevance Based on our findings, a moth-eaten ultrasonographic appearance of the spleen in cats does not necessarily reflect a lymphoma or another malignant neoplastic process on cytological analysis. The presence of a splenic mass >1 cm on ultrasound is suggestive of malignancy in cats. Finally, the transducer frequency must be taken into account when assessing the splenic parenchyma, as a high-frequency transducer seems to improve the detection of a marbled or moth-eaten parenchyma.

Evaluation of hypofunctioning thyroid nodules with technetium-99m MIBI and ultrasonography

Background: Fine needle aspiration cytology (FNAC) cannot reliably differentiate follicular adenoma from follicular carcinoma (FC), which requires histological evidence of capsular or vascular invasion. FC is the most predominant thyroid cancer in our loco-regional environment, indicating the need for improvement in preoperative diagnostic accuracy of thyroid nodules to ensure appropriate and timely interventions.Objective: The purpose of this study was to assess the role of technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) scintigraphy and ultrasonography (USG) in the differential diagnosis of thyroid nodules.Methods: Forty-two patients with hypofunctioning thyroid nodules were prospectively studied with 99mTc-MIBI scintigraphy and USG to differentiate benign from malignant nodules. An injection of 740 MBq of 99mTc-MIBI was intravenously administered, followed by semiquantitative analysis of dual-phase scans using a 4-point (0 to 3) scoring system. USG was subsequently performed and interpretation was based on some sonographic criteria for malignancy. In the following days and weeks, patients underwent FNAC followed by surgery and histopathologic examination.Results: All malignant nodules were positive on 99mTc-MIBI and all but two malignant nodules were positive on USG. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy are, respectively, 100%, 70%, 65%, 100%, and 81% for 99mTc-MIBI scintigraphy; 87%, 78%, 68%, 91% and 81% for USG; and 83%, 100%, 100%, 96% and 64% for FNAC. There was no statistically significant difference between 99mTc-MIBI scintigraphy and USG performance for both benign (p = 0.317) and malignant (p = 0.573) nodules.Conclusion: 99mTc-MIBI scintigraphy and USG are important imaging modalities in the evaluation of thyroid nodules, particularly follicular neoplasms which are frequently associated with non-diagnostic cytology.

A Subhepatic Calcified Cyst

Question: A 68-year-old woman, asymptomatic, with no medical history, underwent an abdominal computed tomography scan in a traumatic context. An enhanced series (Figure A) revealed a 4-cm cystic mass with tissue and calcified rim components located under the left liver (Figure A, arrow) inside the ligamentum teres. The lesion was supplied by a left hepatic artery branch. The frontal view showed the mass drainage into the left external iliac vein through a long pedicle (the umbilicus vein connected to the left inferior epigastric vein) (v). A laparoscopic resection of this mass was performed because of the risk of spontaneous hemorrhage linked to the dense tumoral vasculature and the lack of formal histologic diagnosis. During the procedure, the surgeon observed a cystic mass attached to ligamentum teres between the liver and the umbilicus. At pathologic examination (Figure B), a well-circumscribed largely cystic mass, with a fibrous and calcified shell and hemorrhagic modifications (arrow) was observed. Histologically (Figure C), the fibrous wall contained many large vessels and a small cellular area (star). This area consisted of small nests of moderate-sized monotonous clear cells with normochromatic ovoid nuclei. There was no nuclear atypia and no mitosis. The tumor exhibited an elaborate network of small capillaries. Tumor cells expressed the melanocytic marker HMB45 and smooth muscular actin. What is your diagnosis? Look on page 489 for the answer and see the Gastroenterology website (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and images in GI. PEComas are tumors derived from epithelioid perivascular cells that typically coexpress smooth muscle and melanocytic markers. The family of PEComas includes angiomyolipoma, clear cell “sugar” tumor, and lymphangioleiomyomatosis. Some of these tumors may be associated with tuberous sclerosis complex. PEComas of the ligamentum teres (also called in this location “clear cell myomelanocytic tumors”) are rare, but the ligamentum teres location is the most classic in children. Thirteen cases have been reported in the literature, within or in the immediate vicinity of falciform ligament/ligamentum teres.1Folpe A.L. Goodman Z.D. Ishak K.G. et al.Clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres: a novel member of the perivascular epithelioid clear cell family of tumors with a predilection for children and young adults.Am J Surg Pathol. 2000; 24: 1239-1246Crossref PubMed Scopus (201) Google Scholar, 2Folpe A.L. Mentzel T. Lehr H.A. et al.Perivascular epithelioid cell neoplasms of soft tissue and gynecologic origin.Am J Surg Pathol. 2005; 29: 1558-1575Crossref PubMed Scopus (679) Google Scholar, 3Alaggio R. Cecchetto G. Martignoni G. et al.Malignant perivascular epithelioid cell tumor in children: description of a case and review of literature.J Pediatr Surg. 2012; 47: 31-40Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar There was a marked female predominance with a mean age of 20 years (range, 3-54), a mean size of 8 cm (range, 5-20), and a significant risk of metastasis (3 of 13 cases). Many of the lesions were calcified and had hemorrhagic and cystic alterations. In the absence of established malignancy criteria, PEComas must be considered to have an uncertain malignant potential, requiring surgical resection and long-term monitoring. A mass of the ligamentum teres should always lead to consider the diagnosis of PEComa, even in adults, and even with cystic presentation. Moreover, most frequently, other tumors of the ligamentum teres are malignant (local extension of hepatocellular carcinoma, metastatic adenocarcinoma of gastrointestinal or gynecological origin). The patient was free of disease at 6 months follow-up.