Microscopic Examination of Clots from Percutaneous Mechanical Embolectomies in Pulmonary Embolism.

Pulmonary embolism (PE) is a very common clinical entity with clinical symptoms that range from no symptom to complete hemodynamic collapse, sometimes with similar-appearing clot burden on computed tomographic pulmonary angiogram. Given highly variable clinical presentation, the authors wanted to investigate if there is clinical correlation based on the age of a clot with microscopic examination to clinical presentation. Thirteen thrombectomy aspirates from patients with an acute PE were microscopically analyzed. The goal was to age the thrombus based on histologic features and correlate it to clinical course.

Lymphoid malignancy-associated hemophagocytic lymphohistiocytosis: Search for the hidden source.

Secondary hemophagocytic lymphohistiocytosis (HLH) is an uncommon, but life-threatening syndrome of highly stimulated and ineffective immune dysregulation. It is not a disease entity by itself and the current diagnosis of secondary (acquired) HLH is based on constellation of nonspecific clinical and laboratory parameters indicative of overactive immune response. The presenting symptoms are often nonspecific and could potentially be missed, leading to a fatal outcome. Patients with malignancy-associated HLH have a relatively unfavorable overall survival compared with non-malignancy-associated HLH. In this retrospective study, nine adult patients with secondary HLH were identified. Of these four cases were associated with a malignancy and despite a high degree of suspicion, the underlying lymphoid malignancy was not initially evident. Three out of four patients with lymphoid malignancy-associated HLH died over a very short course of time following the diagnosis. The outcome was significantly different for the control group of patients with other underlying cause(s) for HLH. These cases emphasize the importance of a thorough search for a hidden malignant source in patients with secondary HLH for prompt diagnosis and institution of malignancy specific treatment.

Adrenal cortical adenoma arising in the setting of renal-adrenal fusion: a case report and review of the literature.

BACKGROUND: Renal-adrenal fusion is a rare entity resulting from incomplete encapsulation of the adrenal gland and kidney. Only 18 cases have been reported in English literature to date. CASE PRESENTATION: Our patient is a 77-year-old African American female who presented with a systolic blood pressure of 200 mmHg. Computed tomography showed an enhancing 9 × 6 cm mass anterior and medial to the left kidney. The patient underwent a left adrenalectomy with partial nephrectomy. Gross and histologic examinations revealed an adrenal cortical adenoma and renal-adrenal fusion. CONCLUSION: Renal-adrenal fusion may pose a diagnostic challenge, particularly when there is a concurrent adrenal adenoma. It is important to be aware of this uncommon anomaly to avoid misdiagnosis and overtreatment.

Beyond Clots in the Pulmonary Circulation: Pulmonary Artery Tumors Mimicking Pulmonary Embolism.

Pulmonary embolism (PE) is the most common filling defect seen on CT scan pulmonary angiography. Pulmonary artery (PA) tumors can mimic PE on imaging and clinical presentation. One classic feature of tumors is failure to improve on anticoagulation. PA tumors, particularly malignant ones, have radically different treatments and usually have a grim prognosis. Thus, it is essential that PA tumors, when suspected, receive an expedited confirmatory diagnosis followed by multidisciplinary treatment at an expert center. In this review, we present clinical, imaging, and histopathologic features of benign and malignant PA tumors, emphasizing differentiating features from PE. We also describe available diagnostic and treatment methods for PA tumors.

Ovarian steroid cell tumor associated with von Hippel-Lindau syndrome: a report of two cases and literature review.

Steroid cell tumor (SCT) is a rare sex cord-stromal tumor accounting for only 0.1% of ovarian tumors. Steroid cell tumor, not otherwise specified (SCT, NOS) is of uncertain lineage and is the most common among the three subtypes of SCT. Patients often present with endocrine abnormalities. Von Hippel-Lindau (VHL) syndrome is an autosomal dominant disorder resulting from inactivating gene deletions, frameshifts, and missense mutations of the VHL gene. VHL syndrome can involve multiple organs and clinically is subclassified into type 1 and type 2 based on the risk of pheochromocytoma (PCC). The association of VHL syndrome with genital tract tumors is rare, and here we report two cases of SCT, NOS in patients with VHL disease. The first case is a 19-year old female with VHL and prior resection of bilateral cerebellar hemangioblastomas. During the radiological surveillance, she was found to have multiple small enhancing foci in the cerebellar hemispheres and a stable small enhancing focus in the T6 cord with associated edema, likely reflecting a small hemangioblastoma. She had long history of irregular menses and ultrasound of pelvis found a large right ovarian mass. Cystectomy specimen showed a 6.4 cm well-circumscribed lesion with yellow cut surface. Histologic examination and immunohistochemical staining confirmed the diagnosis of SCT, NOS. The second patient is a 39-year-old female with VHL, previous surgery for retinal hemangioblastomatosis and cerebellar hemangioblastoma, history of abnormal uterine bleeding and elevated testosterone. CT of abdomen and pelvis revealed bilateral multiple cystic and solid renal lesions and a large left ovarian complex cyst. Bilateral partial nephrectomy showed multiple renal cysts and clear cell renal cell carcinomas (RCCs). Left salpingo-oophorectomy showed a 7 cm lesion with yellow-orange cut surface and features consistent with SCT, NOS. Review of the previously reported VHL SCT cases (not including the current two cases) indicated a probable link between VHL syndrome and SCT.

Bone Tumors Occurring in the Soft Tissues: A Review of the Clinical, Imaging, and Histopathologic Findings.

Although rare in everyday practice, malignancies that classically arise from bone or cartilage have been reported to arise de novo in various soft tissues in the body, resulting in a diagnostic challenge for the clinician, radiologist, and pathologist. Differential diagnoses of bone tumors often depend on anatomic location of the lesion. For example, the classic location of osteosarcoma is in the metaphysis of long bones about the knee. Histologically osteosarcoma is characterized by tumor cells that directly produce osteoid, bone, or cartilaginous matrix. In extraskeletal osteosarcoma, the clinical and radiologic picture is very different from a conventional osteosarcoma. They occur in older patients, present as a soft tissue mass often coincidentally following trauma and have a worse prognosis. The imaging characteristics are often nonspecific with mineralized elements in a well-defined soft tissue mass. The mineralized elements may or may not be visible. Magnetic Resonance sequences demonstrate a well circumscribed soft tissue mass with hemorrhagic and enhancing solid components. The pathologic features of extraskeletal osteosarcoma on a microscopic scale are identical to that of skeletal lesions. Likewise, conventional chondrosarcomas present in older patients with a growing, painful soft tissue prominence most commonly involving the long tubular bones. In extraskeletal chondrosarcoma however, the presentation is in somewhat younger patients with a painful soft tissue prominence typically in the head (meninges), neck, or upper leg. The pathologic features are most often that of a myxoid chondrosarcoma which is characterized by strands of small cells over a myxoid matrix. Imaging features include chondroid matrix, heterogenous contrast enhancement, and amorphous internal calcification on Computed Tomography. On Magnetic Resonance sequences the matrix has a low signal on all sequences, and variable inhomogeneity depending on grade of the lesion. Other extraskeletal bone tumors include Ewing's sarcoma and osteoid osteoma amongst other lesions. Although these malignancies may be rare clinical entities, they often exhibit characteristic clinical, imaging, and histopathological findings although differing in treatment and prognosis. Knowledge of these and other common mimicking lesions will help guide the clinician and radiologist to make an accurate diagnosis.

Pulmonary vasculopathy in explanted lungs from patients with interstitial lung disease undergoing lung transplantation.

BACKGROUND: Pulmonary hypertension (PH) causes increased morbidity and mortality in patients with interstitial lung diseases (ILD). Classification schemes, while well-characterised for the vasculopathy of idiopathic PH, have been applied, unchallenged, to ILD-related PH. We evaluated pulmonary arterial histopathology in explanted human lung tissue from patients who were transplanted for advanced fibrotic ILD. METHODS: Lung explants from 38 adult patients who underwent lung transplantation were included. Patients were divided into three groups: none, mild/moderate and severe PH by mean pulmonary artery pressure (mPAP) measured at pre lung transplantation right heart catheterisation (RHC). Grading of pulmonary vasculopathy according to Heath and Edwards scheme, and prelung transplantation evaluation data were compared between the groups. RESULTS: 38 patients with fibrotic ILDs were included, the majority (21) with idiopathic pulmonary fibrosis. Of the 38 patients, 18 had severe PH, 13 had mild/moderate PH and 7 had no PH by RHC. 16 of 38 patients had severe pulmonary arterial vasculopathy including vascular occlusion with intimal fibrosis and/or plexiform lesions. There were no correlations between mPAP and lung diffusion with the severity of pulmonary arterial pathological grade (Spearman's rho=0.14, p=0.34, rho=0.11, p=0.49, respectively). CONCLUSIONS: Patients with end stage ILD had severe pulmonary arterial vasculopathy in their explanted lungs irrespective of the presence and/or severity of PH as measured by RHC. These findings suggest that advanced pulmonary arterial vasculopathy is common in patients with advanced fibrotic ILD and may develop prior to the clinical detection of PH by RHC.

Clinical predictors and explant lung pathology of acute exacerbation of idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is characterised by constant threat of acute exacerbation of IPF (AE-IPF). It would be significant to identify risk factors of AE-IPF. We sought to determine the prognostic value of lung transplantation candidacy testing for AE-IPF and describe explant pathology of recipients with and without AE-IPF before lung transplantation. METHODS: Retrospective cohort study of 89 IPF patients listed for lung transplantation. Data included pulmonary function testing, echocardiography, right heart catheterisation, imaging, oesophageal pH/manometry and blood tests. Explanted tissue was evaluated by pulmonary pathologists and correlated to computed tomography (CT) findings. RESULTS: Out of 89 patients with IPF, 52 were transplanted during stable IPF and 37 had AE-IPF before transplantation (n=28) or death (n=9). There were no substantial differences in candidacy testing with and without AE-IPF. AE-IPF had higher rate of decline of forced vital capacity (FVC) (21±22% versus 4.8±14%, p=0.00019). FVC decline of >15% had a hazard ratio of 7.2 for developing AE-IPF compared to FVC decline of <5% (p=0.004). AE-IPF had more secondary diverse histopathology (82% versus 29%, p<0.0001) beyond diffuse alveolar damage. There was no correlation between ground-glass opacities (GGO) on chest CT at any point to development of AE-IPF (p=0.077), but GGO during AE-IPF predicted secondary pathological process beyond diffuse alveolar damage. CONCLUSIONS: Lung transplantation candidacy testing including reflux studies did not predict AE-IPF besides FVC absolute decline. CT did not predict clinical or pathological AE-IPF. Secondary diverse lung pathology beyond diffuse alveolar damage was present in most AE-IPF, but not in stable IPF.

Salivary gland epithelial neoplasms in pediatric population: a single-institute experience with a focus on the histologic spectrum and clinical outcome.

Salivary gland epithelial neoplasms are rare in children and adolescents, with only a handful of large series having been published. A retrospective study was conducted for 57 cases in patients 20 years or younger. The tumors were located in the parotid (n=36), submandibular gland (n=7), and minor salivary glands (n=14). Nineteen (33%) tumors were pleomorphic adenoma, whereas the remaining (67%) were malignant. The histologic types of carcinomas were mucoepidermoid carcinoma (MEC, n=19, 33%), acinic cell carcinoma (n=7, 12%), adenoid cystic carcinoma (n=6, 11%), secretory carcinoma (mammary analogue) (SC, n=4, 7%), and myoepithelial carcinoma (n=2, 4%). Ninety-three percent (13/14) of the minor and 58% (25/43) of the major salivary gland tumors were malignant. A 7-year-old girl (2%) with a high-grade MEC died from her disease because of uncontrollable locoregional recurrence. Seven patients (16%) developed recurrence including 2 distant metastases from adenoid cystic carcinoma and 6 locoregional recurrences (2 pleomorphic adenomas, 1 SC, 1 myoepithelial carcinoma, 1 adenoid cystic carcinoma, and 1 MEC). The following parameters were associated with decreased disease-free survival in malignant tumors: elevated mitotic index of >4/10 high-power fields (log-rank test, P<.001), and advanced American Joint Committee on Cancer pT (P=.029) and pN stage (P<.001). In conclusion, myoepithelial carcinoma and SC can occur in the pediatric population and should be considered in the differential diagnosis. Salivary gland malignancies in children appear to have better clinical outcome, associated with a 10-year recurrence-free survival rate of 74% and a 10-year disease-specific survival of 94%.

Novel High-grade Endometrial Stromal Sarcoma: A Morphologic Mimicker of Myxoid Leiomyosarcoma.

Endometrial stromal sarcomas (ESS) are often underpinned by recurrent chromosomal translocations resulting in the fusion of genes involved in epigenetic regulation. To date, only YWHAE-NUTM2 rearrangements are associated with distinctive high-grade morphology and aggressive clinical behavior. We identified 3 ESS morphologically mimicking myxoid leiomyosarcoma of the uterus and sought to describe their unique histopathologic features and identify genetic alterations using next-generation sequencing. All cases displayed predominantly spindled cells associated with abundant myxoid stroma and brisk mitotic activity. Tumors involved the endometrium and demonstrated tongue-like myometrial infiltration. All 3 were associated with an aggressive clinical course, including multisite bony metastases in 1 patient, progressive peritoneal disease after chemotherapy in another, and metastases to the lung and skin in the last patient. All 3 ESS were found to harbor ZC3H7B-BCOR gene fusions by targeted sequencing and fluorescence in situ hybridization. On the basis of the review of these cases, we find that ESS with ZC3H7B-BCOR fusion constitutes a novel type of high-grade ESS and shares significant morphologic overlap with myxoid leiomyosarcoma.

Undiagnosed fatal malignancy in adult autopsies: a 10-year retrospective study.

Autopsies reveal undiagnosed malignancies even in this era of modern diagnostic imaging and ancillary laboratory studies. The incidence of clinically undiagnosed malignancies related to primary cause of death in a university hospital setting has rarely been studied. Our objective was to determine the incidence of clinically undiagnosed fatal malignancies in an urban teaching hospital and to assess whether this incidence was influenced by the duration of hospital stay. We performed a retrospective analysis of consecutive adult hospital autopsies in which the primary cause of death was related to undiagnosed malignancy. The detailed autopsy report, clinical records, and relevant laboratory results from laboratory and hospital databases were reviewed. Eight hundred twenty-one adult autopsies were performed over 10 years. Sixty-nine clinically undiagnosed malignant neoplasms were found in 66 cases (8%). In 26 of these 66 cases, the undiagnosed malignant neoplasm was related to the primary cause of death (3.1%). The duration of hospital stay was less than 24 hours in 8 cases (30.7%), 2 to 7 days in 9 cases (34.6%), and greater than 7 days in 9 cases (34.6%). In 10 of these 26 cases (1.2%), there was suspicion of malignancy without definitive tissue diagnosis, and the average hospital stay was 4.9 days. In 16 (1.9%) of these 26 cases, malignancy was not clinically suspected, and the average hospital stay was 9.9 days. We conclude that despite the recent advances in diagnostic imaging and laboratory techniques, a subset of adult autopsies (3.1%) performed in an urban university hospital have clinically undiagnosed malignancy related to the primary cause of death. Malignancy was not clinically suspected in 1.9% of these cases. There is a need to conduct comprehensive "root cause" analysis in these cases for improvement of clinical care.

Predictors of Outcome in the Phenotypic Spectrum of Polymorphous Low-grade Adenocarcinoma (PLGA) and Cribriform Adenocarcinoma of Salivary Gland (CASG): A Retrospective Study of 69 Patients.

Polymorphous low-grade adenocarcinoma (PLGA) shows histologic diversity with fascicular and targetoid features while cribriform adenocarcinoma of salivary gland (CASG) demonstrates predominant cribriform and solid patterns with glomeruloid appearance and optical clear nuclei. The current study is designed to identify pathologic features that may predict clinical outcome in 69 PLGA/CASG. Seven patients had recurrences or distant metastasis, including 3 local recurrences, 2 nodal metastases, and 2 distant metastases. The following histologic factors predicted disease-free survival on univariate analysis: tumor size, bone invasion, lymphovascular invasion, tumor necrosis, ≥10% papillary pattern, and ≥30% cribriform pattern. On multivariate analysis, 10% of papillary pattern and 30% cribriform pattern were independent prognostic factors of disease-free survival. Histologic classification of the 69 tumors (based on the prior reported definition of CASG) showed 21 CASGs (30%), 23 PLGAs (33%), and 22 (32%) with indeterminate features of PLGA and CASG. In addition, 3 (4%) tumors demonstrated a predominant papillary pattern (≥50%). Interestingly, not all CASGs were located in the minor salivary gland and 2 tumors were identified in the parotid. One patient died from her disease and she harbored a CASG with >30% cribriform pattern. In conclusion, tumor size, bone invasion, and lymphovascular invasion are significant parameters that can predict adverse clinical behaviors in PLGA/CASG on univariate analysis. Using the prior reported definition, an overlapping histology between PLGA and CASG was noted in over a third of the cases. Regardless of tumor subclassification, the percentage of cribriform and papillary patterns seems to be prognostically relevant and should be documented.

Testicular seminomatous mixed germ cell tumor with choriocarcinoma and teratoma with secondary somatic malignancy: a case report.

INTRODUCTION: Testicular tumors are a heterogeneous group of neoplasms exhibiting diverse histopathology and can be classified as seminomatous and non-seminomatous germ cell tumor types. Mixed germ cell tumors contain more than one germ cell component and various combinations have been reported. Here, we present a rare case of a mixed germ cell tumor composed of seminoma, choriocarcinoma and teratoma with a secondary somatic malignancy. CASE PRESENTATION: A 31-year-old Caucasian man presented with splenic rupture to our hospital. A right-sided testicular swelling had been present for 6 months and his alpha-fetoprotein, beta-human chorionic gonadotropin, and lactose dehydrogenase were increased. An ultrasound of his scrotum revealed an enlarged right testis with heterogeneous echogenicity. Multiple hypervascular lesions were noted in his liver and spleen. He underwent transcatheter embolization therapy of his splenic artery followed by splenectomy and right-sided orchiectomy. A computed tomography scan also showed metastasis to both lungs. During his last follow up after four cycles of cisplatin-based chemotherapy, the level of tumor markers had decreased, decreases in the size of his liver and pulmonary lesions were noted but new sclerotic lesions were evident in his thoracolumbar region raising concern for bony metastasis. CONCLUSIONS: Prognosis of testicular tumor depends mainly on the clinical stage, but emergence of a sarcomatous component presents a challenge in the treatment of germ cell tumors and the histological subtype of this component can be used as a guide to specific chemotherapy in these patients.

Aggressive Subcutaneous Panniculitis-Like CD30+ Peripheral T-Cell Lymphoma with Diffuse EBER Expression.

T-cell lineage lymphoma with an intense membranous and paranuclear CD30 expression in the absence of ALK1 raises a differential diagnosis of peripheral T-cell lymphoma (PTCL), NOS and anaplastic large cell lymphoma (ALCL), ALK negative. However, Epstein-Barr virus is consistently negative in ALCL and is not considered an implicating factor in its pathogenesis. We describe a case of T-cell lymphoma showing anaplastic large cell morphology with scattered hallmark cells and a uniform CD30 and Epstein-Barr virus encoded early RNA (EBER) expression that primarily involved the subcutaneous tissue at presentation. On incisional biopsy, the neoplastic cells were positive for CD3, CD2, and CD30 while negative for LCA, CD20, PAX5, CD56, ALK1, and cytotoxic granules. Molecular analysis identified a positive T-cell receptor (beta and gamma) gene rearrangement by PCR. Proliferation index approached 100% and the patient had a rapidly progressive course; the subcutaneous lesions more than doubled in size within couple of weeks with new evidence for widespread systemic involvement. This case emphasizes a rare EBV association with a CD30 positive T-cell lymphoma where the morphologic and immunophenotypic findings are otherwise nondiscriminatory between PTCL, NOS and ALCL, ALK negative.