Establishing an Anatomic Pathology Laboratory at Cleveland Clinic Abu Dhabi.

CONTEXT: - The Department of Anatomic Pathology is a division of the Pathology & Laboratory Medicine Institute at Cleveland Clinic Abu Dhabi. The hospital offers the same model of care as its US-based counterpart the Cleveland Clinic, established in 1921 in Cleveland, Ohio. Pathology services at Cleveland Clinic are internationally acclaimed: the endeavor for Cleveland Clinic Abu Dhabi was to create a parallel facility, with the same standards in a greenfield start-up environment. OBJECTIVE: - To narrate how we addressed challenges customary in any laboratory start-up and issues distinctive to our setting with the aim to provide a model for others involved in a similar undertaking. DATA SOURCES: - All information in this article is based on published literature obtained by search on internet-based search engines, Clinical and Laboratory Standards Institute, and the authors' firsthand experience. CONCLUSIONS: - Key considerations in establishing an anatomic pathology laboratory are careful planning and design, adherence to local and international regulatory standards, selection of equipment and supplies, appropriate staffing, development of a laboratory information system, and sound test validation. In addition to meeting our clinical needs, alliance with the US Cleveland Clinic had an integral role in establishing our laboratory and regional reputation.

Setting Up an ePathology Service at Cleveland Clinic Abu Dhabi: Joint Collaboration With Cleveland Clinic, United States.

CONTEXT.­: The production of whole slide images is the most advanced form of digital pathology, in which a high-resolution digital scanner is used to rapidly scan glass microscope slides and produce a computer-generated whole slide image that can be saved, stored in a network-attached storage device, and accessed through slide management software within the hospital domain and remotely by authorized users. Digital transformation of glass slides has revolutionized the practice of anatomic pathology by facilitating and expediting consultative services, improving clinical workflow, and becoming an indispensable tool in education and research. OBJECTIVE.­: To highlight the institutional need of Cleveland Clinic Abu Dhabi (Abu Dhabi, United Arab Emirates) and the cultural background for obtaining the United Arab Emirates' first comprehensive digital pathology program; to describe a multiphase road map for achieving full implementation of this platform; and to describe the system's clinical applications and its future potential growth. DATA SOURCES.­: At Cleveland Clinic Abu Dhabi, we prioritized our efforts to initiate digital consultations (eConsultations) and digital immunohistochemistry services (eIHC) with Cleveland Clinic Laboratories (Cleveland, Ohio). After this, we established an internal archiving system together with a subspecialty-based, organ-specific digital library of pathologic diseases. CONCLUSIONS.­: We describe the strategic adoption and implementation of digital pathology into the clinical workflow of the pathology and laboratory medicine institute of Cleveland Clinic Abu Dhabi, and we highlight its impact on clinical operations, educational activities, and patient care.

Rare Aggressive Calvarial Osteoblastoma with Dural Invasion.

We report a rare case of an aggressive osteoblastoma (OB) involving the calvaria and infiltrating the dura, a finding that was not previously reported in the literature. A 50-year-old man presented with a progressive mass in the left frontoparietal skull with headaches and a six-month history of sudden mass growth. Computed tomography (CT) and magnetic resonance imaging (MRI) showed a large skull lesion with areas of hemorrhage, calcification, restricted diffusion, and enhancement.  A left temporoparietal craniotomy with a complete resection of the tumor with grossly clean margins was performed. Follow-up at 60 months showed a stable clinical picture and no sign of local recurrence of the lesion on MRI.

Substrain-specific differences in bone parameters, alpha-2-macroglobulin circulating levels, and osteonecrosis incidence in a rat model.

Osteonecrosis of the femoral head (ONFH) is a potentially devastating complication that occurs in up to 40% of young adults receiving chronic glucocorticoid (GC) therapy. Through a validated GC therapy rat model, we have previously shown that Wistar Kyoto (WK) rats exhibit a genetic susceptibility to GC-induced ONFH compared to Sasco Fischer (F344) rats. We have undertaken this study in order to investigate differences between these two strains for their bone parameters, alpha-2-macroglobulin (A2M) circulating levels and incidence of GC-induced osteonecrosis of the femoral head. WK and F344 rats were treated either with 1.5 mg/kg/day of prednisone or placebo for 6 months. Blood was taken every month. The femoral heads were harvested for histological examination to detect ONFH and analyzed with micro-computed tomography. After 3 months of GC-therapy, plasma A2M was elevated in treated rats only. GC-treated WK rats exhibited histological evidence of early ONFH through higher rates of cellular apoptosis and empty osteocyte lacunae in the subchondral bone compared to placebos and to F344 rats. Furthermore, micro-CT analysis exhibited femoral head collapse only in GC-treated WK rats. Interestingly, GC-treated F344 rats exhibited significant micro-CT changes, but such changes were less concentrated in the articular region and were accompanied histologically with increased marrow fat. These µCT and histological findings suggest that elevated A2M serum level is not predictive and suitable as an indicative biomarker for early GC-induced ONFH in rodents. Elevated A2M levels observed during GC treatment suggests that it plays role in the host reparative response to GC-associated effects. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1183-1194, 2017.

Urine cytology: does the number of atypical urothelial cells matter? A qualitative and quantitative study of 112 cases.

INTRODUCTION: This study presents a detailed and systematic morphological and quantitative analysis of urine cytology specimens in order to determine which qualitative and quantitative features are mostly associated with high-grade urothelial carcinoma (HGUCA). MATERIAL AND METHODS: This study included 112 urine cytology cases with a surgical follow-up within 1 year that were originally reported as "atypical," "suspicious for HGUCA," or "positive for HGUCA." The morphological characteristics as well as the number of abnormal cells were correlated with a diagnosis of HGUCA on follow-up biopsy. RESULTS: Multivariate analysis showed that the presence of hyperchromatic atypical cells with nuclear-cytoplasmic ratio ≥ 0.7 was an independent predictor of HGUCA. Similarly, irregular nuclear membranes, single cells, and pleomorphism correlated with surgical outcome whereas eccentric nuclear location, prominent nucleoli, nuclear-cytoplasmic ratio between 0.5 and 0.7 did not. Cases with ≤10 atypical cells had significantly lower rates of subsequent HGUCA than did those with >10 atypical cells (58% versus 77%). Cases with ≤5 atypical cells (n = 26) showed similar prediction rates (58%) for HGUCA than did those with 6 to 10 atypical cells (n = 12). CONCLUSIONS: The number of atypical urothelial cells is an important criterion that should be taken into account when assigning cases to the "positive" or the "suspicious" categories. A preliminary cutoff of 10 cells appears to be easily applicable and valid from the clinical standpoint.

Penile metastasis from rectal cancer by PET/CT.

It is extremely rare for rectal tumors to metastasize to the penis, and when it occurs, it is associated with poor prognosis. The appearance of penile metastasis from rectal primary tumor on PET imaging has not been widely reported. We report a case of a 70-year-old man with previous history of treated stage III adenocarcinoma of the rectum 26 months ago. The restaging 18F-FDG PET/CT scan demonstrated a hypermetabolic mass at the base of his penile shaft. This lesion was confirmed on core biopsy to be a metastatic adenocarcinoma of colorectal origin consistent with the known primary rectal tumor.

Imaging characteristics of spindle cell lipoma and its variants.

A spindle cell lipoma (SCL) is a relatively common tumor that can be challenging to the radiologist, pathologist, or surgeon to diagnose, particularly when internal fat content is scant or absent. Although these lesions may be found at various locations, the typical presentation for this lesion is a well-circumscribed and non-aggressive subcutaneous mass in the posterior neck presenting in a middle-aged to elderly man. In this article, the typical and atypical imaging characteristics of a spindle cell lipoma (SCL) will be reviewed. Knowledge of the common imaging and pathologic features of SCLs can help suggest the diagnosis and guide patient management.

Metabolic activity measured on PET/CT correlates with clinical outcomes in patients with limb and girdle sarcomas.

OBJECTIVE: To explore the relationship between metabolic activity and outcome in patients with extremity sarcomas. METHODS: Between June 2004 and December 2011, 120 patients with newly diagnosed limb and girdle sarcomas underwent FDG-PET/CT for disease staging prior to curative intent treatment. The maximum standardized uptake value (SUV(max)) was measured for each primary tumor and correlated with outcome. Progression-free survival and overall survival (OS) were analyzed using the Kaplan-Meier method. RESULTS: Soft-tissue sarcomas were more frequent (68%) than bone (27%) or cartilage (5%) tumors. Median follow-up was 33.2 months. 51% of patients progressed during the follow-up interval and 38% died. SUV(max) was dichotomized with a cut-point of 10.3. Patients with SUV(max) < 10.3 had better DFS and OS compared with patients with SUV(max) ≥ 10.3 (P < 0.001 and P < 0.001, respectively [log-rank test]). Multivariate analysis confirmed that even after adjusting for age, sex, site, tumor type (bone vs. soft-tissue), grade, and stage; an SUV(max) ≥ 10.3 correlated with a twofold risk of progression and 2.4 times greater risk of death (hazard ratio [HR] 2.0, 95% CI, 1.1-3.7, and HR, 2.4, 95% CI, 1.1-4.9). CONCLUSION: SUV(max) is an independent adverse prognostic factor for both progression and OS in patients with extremity sarcomas.

Necrosis on FDG PET/CT correlates with prognosis and mortality in sarcomas.

OBJECTIVE: The purpose of this study was to determine if there is an association between necrosis as identified on staging (18)F-FDG PET/CT and overall survival (OS) and progression-free survival (PFS) in patients with sarcoma. MATERIALS AND METHODS: Sixty-six patients with newly diagnosed limb and girdle sarcoma underwent PET/CT at our institution between June 2004 and July 2009 for sarcoma staging before treatment with curative intent. The tumor maximum standardized up-take values (SUVmax), the presence of necrosis, and the volume of necrosis were measured for each primary tumor and correlated with follow-up data. PFS and OS were analyzed using the Kaplan-Meier method. Proportional hazards models were used to estimate hazard ratios. RESULTS: Median patient age was 49 years, and 51.6% of the patients were men. Sarcomas were categorized as soft tissue (69.2%), bone (23.5%), or other (7.3%). Mean follow-up time was 33.3 months. During the follow-up interval, 53% of patients experienced disease progression, and 40.9% died. There was a statistically significant relationship between the presence of necrosis and OS (by log-rank test, p = 0.001), as well as PFS (by log-rank test, p = 0.0001). Twenty-four-month OS was 96%, 65%, and 38% in patients with tumors with absence necrosis, those with presence of necrosis, and with necrosis volume greater than 50%, respectively. Forty-eight-month OS was 81% in patients with absence of necrosis and 41% in patients with presence of necrosis. Twelve-month PFS was 96%, 60%, and 42% in patients with tumors with absence of necrosis, those with presence of necrosis, and those with necrosis volume greater than 50%, respectively. Twenty-four-month PFS was 83%, 38%, and 22%, respectively, in these groups. CONCLUSION: The presence of necrosis and the volume of necrosis, as identified on the staging FDG PET/CT and after adjusting for SUVmax, are strong independent adverse prognostic factors for disease recurrence and death in patients with limb and girdle sarcomas.

Oral cellular neurothekeoma.

Cellular neurothekeoma is known as a cutaneous tumor with uncertain histogenesis. Very little involvement of mucosal membrane has been reported in the literature so far. This is a case report of an intraoral lesion in a 15-years-old girl. Histopathologic evaluation showed a tumor-consists of spindle to epitheloid cells forming micronodules in a concentric whorled shape pattern. Tumor cells were positive for CD63, vimentin, and NKI-C3. Total excision was performed and no recurrence happened after 16-month followup.

Primitive neuroectodermal tumor (PNET) as somatic-type malignancy arising from an extragonadal germ-cell tumor: clinical, pathological and molecular features of a case.

We report a rare case of a 34-year-old man with a right axillary mass. Ten years previously, he had been diagnosed with a right scapular nonseminomatous germ-cell tumor consisting of teratoma, completely resected without any further treatment. Presently he was found to have a metastatic malignant small round cell tumor consistent with a secondary somatic malignancy arising in the background of nonseminomatous germ-cell tumor, teratoma, yolk sac tumor, and primitive neuroectodermal tumor with distinct chromosome 22 translocation. Although the patient initially responded well to chemotherapy with etoposide, cisplatin, ifosfamide and mesna, he relapsed shortly after.

Soft tissue tumors of the anorectum: rare, complex and misunderstood.

Anorectal soft tissue tumors are uncommon and often present both diagnostic and therapeutic challenges. Although many of these tumors are identified with imaging performed for unrelated reasons, most present with nonspecific symptoms that can lead to a delay in diagnosis. Historically, radical surgery (abdominoperineal resection) has been the mainstay of treatment for both benign and malignant anorectal soft tissue tumors. However, a lack of proven benefit in benign disease along with changes in technology has called this practice into question. In addition, the role of radiation and/or chemotherapy remains controversial. In this manuscript, we review the history and current status of anorectal soft tissue tumor management, with a particular focus on challenges in optimizing survival.

Urinary bladder leiomyosarcoma: staging with 18F-FDG PET/CT.

A 28-year-old woman with a history of prior bilateral retinoblastoma presented with general fatigue, anemia, and a urinary bladder mass seen on abdominal ultrasound and CT. She was referred for a staging 18F-FDG PET/CT, which showed an intensely FDG-avid bladder mass that was biopsied to reveal a leiomyosarcoma, with no evidence of metastases, which guided her management. 18F-FDG PET/CT is routinely used in the evaluation of leiomyosarcomas; however, its use in the staging of a leiomyosarcoma of the urinary bladder has not been previously described in the literature. This case highlights the usefulness of PET/CT in the staging of this rare tumor.

Transoral endoscopic resection of esophageal liposarcoma.

A 63-year-old man presented with a 1-month history of dysphagia. Endoscopy showed the patient had a mass in the cervical esophagus. Multiple biopsy specimens were taken, which were inconclusive for a diagnosis. A positron-emission tomography scan showed a hypermetabolic lesion. A transoral endoscopic approach was used to resect the tumor. Final histologic examination revealed a completely resected low-grade liposarcoma.

Primary perivascular epithelioid cell neoplasm (PEComa) of bone: report of two cases and review of the literature.

Primary perivascular epithelioid cell neoplasms (PEComas) of bone are rare mesenchymal tumors. Histologically, they are composed predominantly of perivascular epithelioid cells and have the capacity to metastasize. PEComas have been reported within intra-abdominal and intra-pelvic organs. To the best of our knowledge, only seven primary PEComas of bone have been described in the English literature. We present two cases of PEComa of bone, one arising from the distal fibula and one from the acetabulum. Both were treated by surgical excision and one also received adjuvant chemotherapy.

Correlating metabolic activity on 18F-FDG PET/CT with histopathologic characteristics of osseous and soft-tissue sarcomas: a retrospective review of 136 patients.

OBJECTIVE: The objective of our study was to determine whether there is a statistically significant correlation between metabolic activity of osseous and soft-tissue sarcomas as measured by the maximum standardized uptake value (SUV(max)) on (18)F-FDG PET/CT and histopathologic characteristics such as mitotic counts, the presence of necrosis, and the presence of a myxoid component. MATERIALS AND METHODS: We retrospectively evaluated 238 consecutive patients with known soft-tissue or osseous sarcoma who underwent (18)F-FDG PET/CT for initial staging or assessment for recurrence of disease. The SUV(max) of each primary or of the most intense metastatic lesion was measured and was compared with the histologic data provided in the final pathology reports. RESULTS: Histopathologic data were available for 136 sarcomas. The median SUV(max) values of sarcomas with mitotic counts of less than 2.00 (per 10 high-power fields [HPF]), 2.00-6.99, 7.00-16.24, and 16.25 or greater were 5.0, 6.6, 10.3, and 13.0, respectively (p = 0.0003). The median SUV(max) for the sarcomas with necrosis (90 patients) was 8.6 and for those without necrosis (43 patients), 6.0 (p = 0.026). The median SUV(max) for the sarcomas without a myxoid component (118 patients) was 7.7 and with a myxoid component (16 patients) was 6.2 (p = 0.28). CONCLUSION: There was a statistically significant correlation between the mitotic count and the SUV(max) as well as between the presence of tumor necrosis and the SUV(max). Although a correlation between the presence of a myxoid component and SUV(max) was shown, it was not found to be statistically significant. These findings improve on the current information in the literature regarding the use of PET/CT for guidance in sarcoma biopsy. Correlating the SUV(max) with histologic markers that also feature prominently in major sarcoma grading systems may help improve the accuracy of grading and of prognostication by allowing the SUV(max) to potentially serve as a surrogate marker in these grading systems, particularly in cases in which there is interobserver disagreement in the pathologic diagnosis or in cases in which the sarcoma cannot be properly classified on the basis of histopathologic evaluation alone.

The appearance of osseous PEComa on F-18 FDG PET/CT.

A 29-year-old male presented with a 6-month history of left hip pain. Radiography and CT demonstrated a 6-cm lytic lesion of the left acetabulum. F-18 FDG PET for staging of the biopsy-proven malignant PEComa demonstrated intense hypermetabolism corresponding to the lytic left acetabulum. The patient underwent left hemipelvectomy with reconstructive surgery. On a follow-up F-18 FDG PET scan 3 months after initial surgery, a left lung pleural-based 9-mm nodule with hypermetabolism (SUVmax 4.1) was discovered and pathologically proven to be metastases from the primary osseous PEComa.

Giant Cell Tumor Pulmonary Metastases Mimic Primary Malignant Pulmonary Nodules on (18)F-FDG PET/CT.

A 59-year-old man with a 30-year history of multiple recurrences of a giant cell tumor (GCT) of the left knee was referred for an (18)F-FDG PET/CT to evaluate a solitary pulmonary nodule. The nodule was mildly FDG-avid, raising suspicion of malignancy. It was excised and histologically proven to be a GCT pulmonary metastasis. A follow-up PET/CT done 2 years later revealed a new, larger lung mass that was more intensely FDG-avid, but of the same histology. This rare report highlights a pitfall in the evaluation of solitary pulmonary lesions by (18)F-FDG PET/CT in patients with GCT of the bone.

Solitary fibrous tumor: an update on the spectrum of extrapleural manifestations.

Solitary fibrous tumor (SFT) is a rare tumor initially believed to be a benign localized pleural tumor of mesothelial origin. Over the past few years, the literature on this tumor has grown tremendously. The tumor is now reported in diverse bodily locations, and recognized to have a wider range of clinical and radiological features. The most common extrapleural sites of the tumor are the orbits and the extremities. Tumors are often well-circumscribed masses, and vary in size from 1 cm to over 30 cm. The admixture of histological components in the tumor, namely, fibrous tissue, cellular components, and highly vascularized areas consisting of numerous closely packed small to medium-sized blood vessels, influence the imaging appearances of the tumor. On magnetic resonance imaging (MRI), the diagnosis of solitary fibrous tumor is suggested by a well-circumscribed mass that has smooth margins, and focal or diffuse hypointense signal on T2-weighted imaging due to fibrous content in the tumor. SFTs demonstrate strong focal or diffuse contrast enhancement due to the highly vascularized areas in the tumor.