Retroperitoneal liposarcoma mimicking pheochromocytoma.

Retroperitoneal liposarcomas are rare mesenchymal tumors which carry a poor prognosis because of their late presentation. When symptoms do occur, they are usually nonspecific and related to mass effect or invasion of local structures. Rarely, retroperitoneal liposarcomas can clinically and biochemically mimic phaeochromocytomas. We discuss one such case of a 56-year-old Afro-Trinidadian female who presented to her primary care physician with a 3-month history of weakness, intermittent sweating, difficulty sleeping and elevated blood pressure. After a 2 week trial of an oral antihypertensive regime her blood pressure was still elevated and she complained of new right sided abdominal pain. A subsequent Computed Tomography scan of her abdomen revealed an enhancing, heterogeneous right suprarenal mass suspicious for pheochromocytoma. Urinary catecholamines were also elevated and an MRI of her abdomen supported the diagnosis of pheochromocytoma although intralesionsal fat was noted, an uncommon feature of pheochromocytomas. She was booked for laparoscopic adrenalectomy. Histological analysis of the resected specimen confirmed a dedifferentiated retroperitoneal liposarcoma. While the imaging features of phaeochromocytomas and retroperitoneal liposarcomas can be similar, the presence of intralesional fat on CT and MRI should favour the diagnosis of a retroperitoneal liposarcoma, albeit the clinical and biochemical picture.

Global Pathology Training in Residency and Fellowship: A Mutually Beneficial Intervention.

CONTEXT.­: Most cancers occur in lower and middle income countries, where pathologists are scarce. Despite this, few pathology training programs offer global health electives, and trainees are not exposed to challenges associated with practicing in resource-restricted settings. OBJECTIVE.­: To implement a global health elective model aimed at exposing trainees to global health while alleviating overburdened pathologists in resource-restricted settings. DESIGN.­: For 1 year, trainees at 2 US institutions reviewed cases shipped weekly from a pathology lab serving Trinidad and Tobago and Guyana. Turnaround time, specimen type, and trainee and clinician satisfaction were assessed. RESULTS.­: Trainees reviewed an average of 16 cases per week. Average turnaround time was 6 days. There was no significant difference between the turnaround time for the US trainees and the pathologist based in the lab in Trinidad. Trainees and clinicians reported a high level of satisfaction, and the collaboration was fruitful, resulting in the publication of a case report. CONCLUSIONS.­: We demonstrate that collaboration between US trainees and laboratories in resource-restricted settings, in the form of a global health elective, is mutually beneficial.

Large left posterior fossa meningioma presenting with quadriplegia in a woman with history of carbidopa-levodopa resistant parkinsonism.

A 56-year-old Afro-Trinidadian woman with a history of a carbidopa-levodopa resistance Parkinsonian-like syndrome for 2 years, presented with acute onset spastic quadriplegia and decreased responsiveness. Diagnosis involved clinical and MR-imaging correlation consistent with a large left posterior fossa meningioma. Surgical removal of the tumor led to complete reversibility of the neurological manifestations associated with cerebellar tonsillar herniation beyond the foramen magnum and mass effect on the brainstem, cerebellum and midbrain regions. Pathological findings were typical of a meningioma. This case demonstrates the association of a large left posterior fossa meningioma and carbidopalevodopa resistant parkinsonism in an Afro-Trinidadian woman who presented with acute onset acute quadriplegia and decreased responsiveness. This case reminds clinicians that patients with dopa unresponsiveness and/or acute neurological deficit or deterioration should be worked up for other possible causes and adds to the literature on the association of parkinsonism and intracranial space occupying lesions.

Epidemiology of salivary gland tumours in an Eastern Caribbean nation: A retrospective study.

OBJECTIVE: The epidemiology of the salivary glands tumour is not well documented in the Caribbean countries. Therefore, the aim of this study is to determine the local trend of salivary gland tumours with a review of current diagnostic techniques. DESIGN & METHODS: Retrospective data was collected from the electronic database at the Pathology department of the San Fernando Teaching Hospital between the periods January 2005 to June 2015. All patients who underwent primary resection of either the parotid, submandibular or minor salivary glands for diagnosed tumour cytologically or suspected tumour were included in this study. The clinical and histopathological data were then collected and analyzed. RESULTS: A total of 85 surgeries were performed for suspected or diagnosed neoplasia, 54 parotidectomies, 26 submandibular gland and 5 minor salivary gland excisions. The benign neoplastic lesions, pleomorphic adenoma and Warthin's tumour, were the most common 53 (62.4%) of all the resections performed, followed by non-neoplastic lesions 25 (29.4%) such as sialadenitis, cysts or normal glands. Malignant neoplasms made up the minority with only 7 cases whereby mucoepidermoid carcinoma was the most common malignant neoplasm found followed by squamous cell carcinoma. CONCLUSION: Parotid gland remains the most frequent site of salivary gland tumours (80%), with pleomorphic adenoma being the most common benign tumour. Triple assessment is still required to manage these cases adequately with stress on preoperative tissue diagnosis FNAB vs USS guided core biopsy.

Giant Cystic Pheochromocytoma with Low Risk of Malignancy: A Case Report and Literature Review.

Giant pheochromocytomas are rare silent entities that do not present with the classical symptoms commonly seen in catecholamine-secreting tumors. In many cases they are accidentally discovered. The algorithm to diagnose a pheochromocytoma consists of biochemical evaluation and imaging of a retroperitoneal mass. The female patient in this case report presented with a palpable abdominal mass and was cured with surgical resection. She suffered no recurrence or complications on follow-up. The left retroperitoneal mass measured 27 × 18 × 12 cm and weighed 3,315 grams. Biochemical, radiological, and pathological examinations confirmed the diagnosis of a pheochromocytoma. In this paper, we report on our experience treating this patient and provide a summary of all giant pheochromocytomas greater than 10 cm reported to date in English language medical journals. Our patient's giant cystic pheochromocytoma was the fourth heaviest and fifth largest maximal diameter identified using our literature search criteria. Additionally, this tumor had the largest maximal diameter of all histologically confirmed benign/low metastatic risk pheochromocytomas. Giant cystic pheochromocytomas are rare entities requiring clinical suspicion coupled with strategic diagnostic evaluation to confirm the diagnosis.

A case report of the clear cell variant of gallbladder carcinoma.

INTRODUCTION: Clear cell gallbladder carcinoma accounts for less than 1% of all gallbladder malignancies and demonstrates its unique histopathological characteristics in patients with no prior medical illness or familial predisposition. PRESENTATION OF CASE: Here we present a case of a 56-year-old female, with no prior medical conditions presented with a 2-month history of upper abdominal pain. Routine hematological and biochemical tests were unremarkable. An abdominal ultrasound revealed the presence of a gallbladder calculi, and a fundic mass while magnetic resonance cholangiopancreatography revealed a 8.0cm×3.5cm gallbladder mass. Computed tomography imaging excluded any distant haematogenous metastases. An open cholecystectomy with lymphadenectomy was proceeded by staging laparoscopy. Upon pathologic investigation, the morphologic and immunophenotypic features supported a diagnosis of clear cell variant of gallbladder carcinoma. DISCUSSION: Pathological prognostications for primary clear cell gall bladder carcinomas are not well defined due to the rarity of cases and possible misidentification as secondary metastases. Foci of adenocarcinoma within the tumor along with immunohistochemical staining probes can be informative in consideration of differential diagnosis. CONCLUSION: In these cases, clinical case management should be personalized for increased survival with the possible incorporation of next generation sequencing approaches to guide therapeutic algorithms. We discuss this exceedingly rare case of the clear cell variant of gallbladder carcinoma in detail, highlighting some of the diagnostic, and clinical challenges.

Rare nodular malignant melanoma of the heel in the Caribbean: A case report.

INTRODUCTION: Malignant melanoma of the heel is a rare melanoma subtype with incidence rates that reflect the complex relationship between sun exposure at certain geographic locations, individual melanin levels and overall melanoma risk. It is oftentimes characterized by poor prognosis because of delays in presentation resulting in longitudinal tumor invasion, lymph node involvement and metastasis. PRESENTATION OF CASE: A 59-year-old woman was admitted to the Eric Williams Medical Sciences Complex, Trinidad and Tobago with a 5mm pruritic lesion on her left heel. At presentation, the lesion was asymmetric with border irregularities, color heterogeneity, with dynamics in elevation and overall size. She was subsequently diagnosed with malignant melanoma with left inguinal lymphadenopathy. A single stage wide local excision (WLE) of the left heel lesion with a split-thickness skin graft (STSG) and a left inguinal lymphadenectomy were performed. Dacarbazine (Bayer) was administered post operatively. DISCUSSION: Globally, the incidence of malignant melanoma is rapidly increasing, particularly, in countries like Trinidad and Tobago with a significant population of non-fair skinned individuals. There is need for strategic initiatives to increase patient adherence in these populations. CONCLUSION: The rarity of malignant heel melanomas heightens the need for increased patient awareness and greater clinical surveillance to ensure early diagnosis and treatment.

Right sided spleen laying retro-duodenal: A case report and review of the literature.

INTRODUCTION: Unlike left sided accessory spleen that are seen in 10-30% of cases at autopsy, cases of right accessory spleens are extremely rare. This congenital body of healthy splenic tissue simulates tumors from neighboring organs and presents a challenge in formulating a differential diagnosis. PRESENTATION OF CASE: We present the case of a patient whose CT scan of the abdomen showed a large mass, 11×8cm, arising retro-duodenal and lying just anterior to the right kidney. To the best of our knowledge, this is the only case where the accessory spleen was found retro-duodenal, directly anterior to the kidney and completely separate from the supra-renal gland. The chief complaint of the patient was right upper quadrant pain, radiating to the back, and colicky in nature. The patient was diagnosed with duodenal gastro-intestinal stromal tumor and a retro-peritoneal sarcoma. The mass was removed via a Kocher's incision and immunohistological examination showed that it was a right sided accessory spleen. The patient's left sided spleen appeared normal. DISCUSSION: Efforts to distinguish an accessory spleen from a retroperitoneal tumor with available scans, percutaneous biopsy or biochemical tests are inconclusive. Differential diagnosis between a retroperitoneal tumor and an accessory spleen can only be made after surgical exploration. CONCLUSION: This case highlights the fact that surgeons should consider the possibility of an accessory spleen when making a differential diagnosis of retroperitoneal tumors.

Clinical validation of a next-generation sequencing screen for mutational hotspots in 46 cancer-related genes.

Transfer of next-generation sequencing technology to a Clinical Laboratory Improvement Amendments-certified laboratory requires vigorous validation. Herein, we validated a next-generation sequencing screen interrogating 740 mutational hotspots in 46 cancer-related genes using the Ion Torrent AmpliSeq cancer panel and Ion Torrent Personal Genome Machine (IT-PGM). Ten nanograms of FFPE DNA was used as template to amplify mutation hotspot regions of 46 genes in 70 solid tumor samples, including 22 archival specimens with known mutations and 48 specimens sequenced in parallel with alternate sequencing platforms. In the archival specimens, the IT-PGM detected expected nucleotide substitutions (n = 29) and four of six insertions/deletions; in parallel, 66 variants were detected. These variants, except a single nucleotide substitution, were confirmed by alternate platforms. Repeated sequencing of progressively diluted DNA from two cancer cell lines with known mutations demonstrated reliable sensitivity at 10% variant frequency for single nucleotide variants with high intrarun and inter-run reproducibility. Manual library preparation yielded relatively superior sequencing performance compared with the automated Ion Torrent OneTouch system. Overall, the IT-PGM platform with the ability to multiplex and simultaneously sequence multiple patient samples using low amounts of FFPE DNA was specific and sensitive for single nucleotide variant mutation analysis and can be incorporated easily into the clinical laboratory for routine testing.

Frequency and spectrum of BRAF mutations in a retrospective, single-institution study of 1112 cases of melanoma.

The US Food and Drug Administration (FDA) approved vemurafenib to treat patients with metastatic melanoma harboring the BRAF c.1799T>A (p.V600E) mutation. However, a subset of melanomas harbor non-p.V600E BRAF mutations, and these data are of potential importance regarding the efficacy of current targeted therapies. To better understand the BRAF mutation profile in melanomas, we retrospectively analyzed data from 1112 primary and metastatic melanomas at our institution. The cohort included nonacral cutaneous (n = 774), acral (n = 111), mucosal (n = 26), uveal (n = 23), leptomeningeal (n = 1), and metastatic melanomas of unknown primary site (n = 177). BRAF mutation hotspot regions in exons 11 and 15 were analyzed by pyrosequencing or with the primer extension MassARRAY system. A total of 499 (44.9%) specimens exhibited BRAF mutations, involving exon 15 [497 (99.6%)] or exon 11 [2 (0.4%)]. p.V600E was detected in 376 (75.4%) cases; the remaining 123 (24.6%) cases exhibited non-p.V600E mutations, of which p.V600K was most frequent [86 (17.2%)]. BRAF mutations were more frequent in nonacral cutaneous (51.4%) than acral melanomas [18 (16.2%)] (P < 0.001); however, there was no significant difference among cutaneous histological subtypes. All mucosal, uveal, and leptomeningeal melanomas were BRAF wild type (WT). The high frequency of non-p.V600E BRAF mutations in melanoma has important implications because the FDA-approved companion diagnostic test for p.V600E detects some but not all non-p.V600E mutations. However, the therapeutic efficacy of vemurafenib is not well established in these lesions.

Detection of ABCC1 expression in classical Hodgkin lymphoma is associated with increased risk of treatment failure using standard chemotherapy protocols.

BACKGROUND: The mechanisms responsible for chemoresistance in patients with refractory classical Hodgkin lymphoma (CHL) are unknown. ATP-binding cassette (ABC) transporters confer multidrug resistance in various cancers and ABCC1 overexpression has been shown to contribute to drug resistance in the CHL cell line, KMH2. FINDINGS: We analyzed for expression of five ABC transporters ABCB1, ABCC1, ABCC2, ABCC3 and ABCG2 using immunohistochemistry in 103 pre-treatment tumor specimens obtained from patients with CHL. All patients received first-line standard chemotherapy with doxorubicin (Adriamycin®), bleomycin, vinblastine, and dacarbazine (ABVD) or equivalent regimens. ABCC1 was expressed in Hodgkin and Reed-Sternberg (HRS) cells in 16 of 82 cases (19.5%) and ABCG2 was expressed by HRS cells in 25 of 77 cases (32.5%). All tumors were negative for ABCB1, ABCC2 and ABCC3. ABCC1 expression was associated with refractory disease (p = 0.01) and was marginally associated with poorer failure-free survival (p = 0.06). Multivariate analysis after adjusting for hemoglobin and albumin levels and age showed that patients with CHL with HRS cells positive for ABCC1 had a higher risk of not responding to treatment (HR = 2.84, 95%, CI: 1.12-7.19 p = 0.028). CONCLUSIONS: Expression of ABCC1 by HRS cells in CHL patients predicts a higher risk of treatment failure and is marginally associated with poorer failure-free survival using standard frontline chemotherapy regimens.

Rapid detection and quantitation of BRAF mutations in hairy cell leukemia using a sensitive pyrosequencing assay.

BRAF protooncogene is an important mediator of cell proliferation and survival signals. BRAF p.V600E mutation was recently described as a molecular marker of hairy cell leukemia (HCL). We developed and validated a pyrosequencing-based approach that covers BRAF mutational hotspots in exons 11 (codon 468) and 15 (codons 595 to 600). The assay detects BRAF mutations at an analytical sensitivity of 5%. We screened 16 unenriched archived bone marrow aspirate samples from patients with a diagnosis of HCL (n = 12) and hairy cell leukemia-variant (HCL-v) (n = 4) using pyrosequencing. BRAF p.V600E mutation was present in all HCL cases and absent in all HCL-v. Our data support the recent finding that BRAF p.V600E mutation is universally present in HCL. Moreover, our pyrosequencing-based assay provides a convenient, rapid, sensitive, and quantitative tool for the detection of BRAF p.V600E mutations in HCL for clinical diagnostic testing.

Glioma-associated oncogene homologue 3, a hedgehog transcription factor, is highly expressed in Hodgkin and Reed-Sternberg cells of classical Hodgkin lymphoma.

The hedgehog signaling pathway has been shown to play a pathogenic role in diffuse large B-cell lymphoma and anaplastic large cell lymphoma, but has not been assessed in classical Hodgkin lymphoma. Glioma-associated oncogene homologues 1, 2, and 3 are transcriptional effectors of the hedgehog pathway. In this study, we first used real-time quantitative polymerase chain reaction to investigate the expressions of GLI1, GLI2, and GLI3 in 3 classical Hodgkin lymphoma cell lines. GLI1 and GLI2 were variably expressed, but GLI3 was highly expressed in all cell lines. We then used immunohistochemistry to assess glioma-associated oncogene homologues 1, 2, and 3 in 39 classical Hodgkin lymphoma patient samples. Glioma-associated oncogene homologues 1 and 2 were weakly to variably expressed in a subset of classical Hodgkin lymphoma patient samples. In contrast, glioma-associated oncogene homologue 3 showed strong, uniform nuclear expression in virtually all Hodgkin/Reed-Stenberg cells. We then performed an immunohistochemical survey of glioma-associated oncogene homologue 3 expression in 13 cases of nodular lymphocyte predominant Hodgkin lymphoma and 218 non-Hodgkin lymphomas. Most other lymphoma types showed variable or no expression of glioma-associated oncogene homologue 3, with a minor subset of cases of nodular lymphocyte predominant Hodgkin lymphoma, ALK-positive and ALK-negative anaplastic large cell lymphoma, and B-cell lymphoma, unclassifiable with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma showing a glioma-associated oncogene homologue 3 staining pattern indistinguishable from classical Hodgkin lymphoma. Our data provide a rationale to further investigate the biologic significance of glioma-associated oncogene homologue 3 in classical Hodgkin lymphoma biology.

Selected topics on lymphoid lesions in the head and neck regions.

Lymphoid tissue located in the head and neck region include multiple regional lymph node chains as well as mucosa associated lymphoid tissue of the conjunctiva, buccal and nasopharyngeal cavities (Waldeyer's ring), and thyroid and salivary glands. This region is a rich source of antigenic stimuli including infectious agents coming from the outside environment. Many reactive conditions that affect lymphoid tissue in this region may mimic neoplasia. In fact, distinguishing between benign and malignant lymphoid proliferations in the head and neck region is a relatively frequent diagnostic challenge and in many instances, this distinction is not straightforward. It therefore behooves the practicing pathologist to be able to recognize the benign lymphoproliferative disorders that affect this region so as to effectively guide the appropriate clinical management of such patients. Kimura disease, Epstein Barr lymphadenitis, HIV associated salivary gland disease and chronic sialadenitis are benign conditions that not infrequently affect lymphoid tissue in the head and neck region and that share certain overlapping features with malignant lymphoma. In this brief review, we discuss these conditions and highlight clinicopathological features that may help distinguish them from neoplastic lymphoproliferations that may share similar features.

Malakoplakia of the spleen: a case report.

Malakoplakia is an uncommon chronic inflammatory disorder, which is characterized by the presence of histiocytes containing concentric concretions known as Michaelis-Gutmann bodies in a background of mixed inflammation. The urinary tract is the most commonly involved site. However, malakoplakia can be found in a wide range of other organs throughout the body. Its occurrence has been attributed to a defect in the bactericidal capacity of phagocytic cells, and it is usually seen in patients with some degree of immunologic compromise. A case of malakoplakia of the spleen in a patient with Crohn's disease is reported in this article.

Comparison of thyroid transcription factor-1 expression by 2 monoclonal antibodies in pulmonary and nonpulmonary primary tumors.

Thyroid transcription factor-1 (TTF-1) is a transcription factor that plays a role in the development and physiology of the thyroid and lungs. Expression of TTF-1 is used as a marker of lung and thyroid clinically. Commercially available clones of TTF-1 monoclonal antibodies, 8G7G3/1 and SPT24, have been reported to have different sensitivities for the detection of neoplasms of different origins. Although they are used extensively in daily practice, a comprehensive comparative study of these antibodies in a wide variety of neoplasms is lacking. We examined TTF-1 expression in primary tumors of the lung, prostrate, pancreas, stomach, salivary glands, breast, bladder, colon, and squamous cell carcinoma of the head and neck and compared the results obtained with both TTF-1 clones. The SPT24 clone detected more primary lung tumors of all histologic subtypes. Importantly, the SPT24 clone detected a significantly higher number of squamous cell carcinomas and carcinoid tumors of the lung. Among nonpulmonary primary tumors, a significant number of invasive urothelial carcinoma of the bladder (5.1%) was TTF-1 positive. In addition, a small proportion of prostate (1.2%), stomach (0.9%), salivary gland (1.8%), and colon (2.5%) carcinomas were positive with both clones. Of note, both clones stained the same nonpulmonary tumors with similar intensity and distribution. Carcinomas of the pancreas, breast, and squamous cell carcinomas of the head and neck were negative with both clones. In summary, the SPT24 clone detected a higher number of pulmonary non-small cell tumors of all histologic subtypes whereas both clones stained a similar proportion of nonpulmonary tumors.