Evan Kulbacki

B-Mode and Acoustic Radiation Force Impulse (ARFI) Imaging of Prostate Zonal Anatomy Comparison with 3T T2-Weighted MR Imaging

Prostate cancer (PCa) is the most common non-cutaneous malignancy among men in the United States and the second leading cause of cancer-related death. Multi-parametric magnetic resonance imaging (mpMRI) has gained recent popularity to characterize PCa. Acoustic Radiation Force Impulse (ARFI) imaging has the potential to aid PCa diagnosis and management by using tissue stiffness to evaluate prostate zonal anatomy and lesions. MR and B-mode/ARFI in vivo imaging datasets were compared with one another and with gross pathology measurements made immediately after radical prostatectomy. Images were manually segmented in 3D Slicer to delineate the central gland (CG) and prostate capsule, and 3D models were rendered to evaluate zonal anatomy dimensions and volumes. Both imaging modalities showed good correlation between estimated organ volume and gross pathologic weights. Ultrasound and MR total prostate volumes were well correlated (R2 = 0.77), but B-mode images yielded prostate volumes that were larger (16.82% ± 22.45%) than MR images, due to overestimation of the lateral dimension (18.4% ± 13.9%), with less significant differences in the other dimensions (7.4% ± 17.6%, anterior-to-posterior, and −10.8% ± 13.9%, apex-to-base). ARFI and MR CG volumes were also well correlated (R2 = 0.85). CG volume differences were attributed to ARFI underestimation of the apex-to-base axis (−28.8% ± 9.4%) and ARFI overestimation of the lateral dimension (21.5% ± 14.3%). B-mode/ARFI imaging yielded prostate volumes and dimensions that were well correlated with MR T2-weighted image (T2WI) estimates, with biases in the lateral dimension due to poor contrast caused by extraprostatic fat. B-mode combined with ARFI imaging is a promising low-cost, portable, real-time modality that can complement mpMRI for PCa diagnosis, treatment planning, and management.

Comparison of concurrently acquired in vivo 3D ARFI and SWEI images of the prostate

In the prostate, ARFI and SWEI imaging methods have reported that cancer and other pathologies as being stiffer than the surrounding tissue. A three-dimensional in vivo prostatic imaging system capable of concurrently acquiring ARFI and SWEI data was developed to compare the information available in the two image types. Data were acquired in a calibrated CIRS phantom to analyze the contrast, contrast to noise ratio (CNR), and resolution between the ARFI and SWEI images; SWEI images provided improved contrast and CNR, but lower spatial resolution than ARFI images. Challenges and potential artifacts in both the ARFI and SWEI images have been identified and reduced by viewing coronal sections and maximum value SWEI images, resulting in high correlation between the normalized ARFI displacement magnitude and the estimated shear wave speed. We have demonstrated that this combined ARFI and SWEI imaging system can image the anatomy of the prostate.

Concomitant Waldenstrom macroglobulinemia and IgA plasmablastic myeloma in a patient with untreated IgM paraproteinemia: sequential development of biclonal B-cell neoplasms over a 10-year period in a single individual.

Waldenstrom macroglobulinemia and plasma cell myeloma are both mature B-cell neoplasms primarily involving bone marrow and frequently demonstrating paraproteinemia. Plasma cell myeloma has been described in association with other indolent B-cell lymphomas, particularly chronic lymphocytic leukemia, but concomitant Waldenstrom macroglobulinemia and plasma cell myeloma has not been previously described. We report the first case of sequential development of Waldenstrom macroglobulinemia and plasma cell myeloma over a 10-year period in a 73-year-old man with untreated IgM paraproteinemia. The bone marrow biopsy demonstrated dual populations of lymphoid cells: small mature lymphocytes and immature plasma cells. Although both Waldenstrom macroglobulinemia and plasma cell myeloma were restricted to κ light chain, plasma cell myeloma expressed IgA, whereas the plasmacytic component in Waldenstrom macroglobulinemia produced IgM. The biclonal nature of these 2 B-cell neoplasms was further supported by immunofixation electrophoresis and cytogenetic studies. Although the clinical outcome of plasma cell myeloma when concomitant with other indolent B-cell neoplasms is unfavorable, our patient seemed to respond to high-dose bortezomib plus lenalidomide.

Merkel cell carcinoma with partial B-cell blastic immunophenotype: a potential mimic of cutaneous richter transformation in a patient with chronic lymphocytic lymphoma.

Merkel cell polyomavirus (MCPyV) is a DNA virus whose pathogenic mechanisms in Merkel cell carcinoma (MCC) are still being unraveled. Emerging reports of an association between MCPyV and chronic lymphocytic lymphoma (CLL) have begun to broaden our understanding of the oncogenic mechanisms of this virus and the known association between these 2 malignancies. Herein, we report a case of MCC demonstrating a B-cell immunophenotype arising in a patient with CLL being treated with rituximab. In this context, we discuss the differential diagnostic considerations, especially with cutaneous Richter transformation (diffuse large B-cell lymphoma). We also assessed for the presence of MCPyV in both the patients MCC and the CLL. Finally, we provide a large meta-analysis of patients with CLL and MCC. Patients with both MCC and CLL have a dismal prognosis, with greater than 50% overall mortality within the first year and a half after MCC diagnosis.

Pathological bone fractures in a 20-year old athletic male with multifocal solitary plasmacytoma of bone.

The patient is a 20-year male who presented for neck pain 2 weeks after he fell while playing football. Commuted tomography (CT) scans revealed a lytic and expansile lesion of the right lateral C1 vertebrae with a linear fracture (Image 1A). The magnetic resonance imaging (MRI) demonstrated a diffuse signal abnormality consistent with a pathologic fracture (Image 1B). After an inconclusive fine needle aspirate examination, the radiological findings were reviewed, and the lesion was thought to be likely an aneurysmal bone cyst. The vertebral fracture was thereafter repaired with a C3 to occiput fusion (Image 1B, inset) withImage 1. Pathological bone fractures caused by multifocal solitary plasmacytoma of bone. A. Horizontal section of CT scan of the neck showing a lytic lesion with a linear fracture of C1 vertebrae (arrow). B. Coronal section of MRI scan showing a diffuse signal abnormality consistent with pathological fracture (arrow) and surgical repair (Inset). C. CT scan showing a large lytic acetabular lesion of right hip (arrow). D. Histological and immunohistochemical studies of right acetabular lesion biopsy showing sheets of plasma cells (D1, H&E stain) which are positive for CD138 (D2) and kappa light chain (D3), but are negative for lambda light chain (D4). E. Urine protein electrophoresis showing Bence Jones protein in gamma region (shaded peak area). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

Synchronous occurrence of metastatic Wilms tumor and ganglioneuroma

We describe a 4‐year‐old female patient with a persistent paraspinal mass following chemotherapy for Wilms tumor. A discordant response to chemotherapy prompted biopsy of the persistent mass, which revealed a ganglioneuroma. This report highlights the synchronous occurrence of different tumors in the same patient, and suggests that repeat biopsies should be considered when contiguous tumor masses do not respond as expected. Pediatr Blood Cancer. 2010;55:562–565.

Anaplastic lymphoma kinase (ALK1) immunohistochemistry in diagnostic dermatopathology; an update.

Abstract:The use of anaplastic lymphoma kinase antibodies (ALK1) as a diagnostic aid has expanded since becoming a routinely available immunohistochemical stain. Because the skin may be the site of a wide variety of hematolymphoid and fibroblastic proliferations, dermatopathologists commonly use ALK1 as part of a broader staining panel in diagnosing soft tissue and cutaneous hematolymphoid neoplasms. Furthermore, new entities and differential diagnostic contexts are emerging, which broaden the utility of ALK1 immunohistochemistry. We review the expanding role of ALK1 immunohistochemistry in contemporary dermatopathology.

Myelomatous meningeal infiltration detected by magnetic resonance imaging.

A 52-year-old male initially presented with moderate anaemia and thrombocytopenia. Bone marrow examination demonstrated 80% plasma cells, with IgA lambda expression. Cytogenetic analysis revealed a complex male karyotype in 2 metaphase cells: 43, XY, del(1)(p13), del(5)(q13q35), add(6)(p25), del(7)(1q31q36), del(8)(p12), add(11)(q23), add(12)(q24.1), 13, 14, 16, +(17)(p11.2), add(18)(q21.1)[2]/46,XY[18]. Markedly elevated serum free lambda light chain and urinary Bence-Jones protein were detected, but renal function was normal and lytic bone lesions were not identified. The patient was diagnosed with plasma cell myeloma, and treated with lenalidomide, bortezomib and dexamethasone, responding well. He remained in remission for 5 months after treatment, and was on maintenance therapy until 6 months from presentation, when a rising serum free lambda light chain signified disease relapse. He was then started on cyclophosphamide, bortezomib and dexamethasone, but showed disease progression despite treatment. Five months after the relapse, the patient presented with diffuse body pain and a sensation of fever and chills, but with no headache, nausea or vomiting. Bone marrow examination showed 85% plasma cells, but circulating neoplastic plasma cells were not identified at the time. He subsequently developed progressive neurological symptoms, including generalised weakness and altered mental status. A computed tomography scan of the head was normal, but magnetic resonance imaging (MRI) demonstrated widespread meningeal enhancement, particularly, a diffuse leptomeningeal FLAIR (Fluid Attenuated Inversion Recovery) hyperintensity along the cerebral sulci (top left and right, arrow heads). The differential diagnosis included meningitis, as well as central nervous system (CNS) involvement by myeloma. A subsequent lumbar puncture revealed elevated protein but normal glucose levels in cerebral spinal fluid (CSF). Cultures and other laboratory tests for bacteria, viruses and fungi were negative. CSF examination demonstrated a marked pleocytosis (cell count 1119/ll; reference: <5) with numerous abnormal plasma cells including many large forms (bottom left). Flow cytometric analysis confirmed the plasma cell lineage with strong expression of CD38 and CD138 (bottom right) without CD19, CD20 or CD56. The diagnosis of CSF myelomatosis was thus rendered. Despite aggressive treatment, the patient deteriorated further and expired 5 days after the diagnosis. Myeloma involving the CNS is considered uncommon, affecting approximately 1% of patients. CSF myelomatosis resembling meningitis on MRI is extremely rare. Neurological manifestations vary from headaches, nausea and vomiting to paraparesis and cranial nerve palsies. The prognosis is very poor.

Diffuse large B‐cell lymphoma with Dutcher bodies

A 61-yr-old female patient was diagnosed with stage IVB diffuse large B-cell lymphoma (DLBCL) and received six cycles of R-CHOP. She had initial response, but was found to have enlarged mammary lymph nodes and several erythematous skin nodules on her left thigh 1 yr after treatment. Biopsies of the skin nodules showed a dense lymphoid infiltrate extending from the deep dermis to the subcutaneous tissue, which spared the epidermis. The infiltrate was composed of medium to large cells with round to irregular nuclei, vesicular chromatin and a moderate amount of cytoplasm (Fig. 1A). Many large cells displayed plasmacytoid features and a minority contained pseudo-nuclear inclusions (Fig. 1A and inset, arrows). Immunohistochemical studies revealed that the large cells stained strongly for CD45, CD79a and Pax5 (Fig. 1B1) with focal positivity for CD20, CD138 and MUM1. The proliferation index was approximately 50% by Ki-67. The large cells were also positive for kappa-light-chain (Fig. 1B2) but were negative for lambda-light-chain (Fig. 1B3). Of note, the pseudo-nuclear inclusions themselves stained for kappa-light-chain (Fig. 1B2, arrows), but were negative for lambda-light-chain (Fig. 1B3, arrows). The large cells were negative for S100 and pancytokeratin by immunostains and negative for EBV by Epstein-Barr Virus-encoded early RNA in situ hybridization. The pseudo-nuclear inclusions were thus recognized as Dutcher bodies, and a diagnosis of recurrent DLBCL with cutaneous involvement was established. Serum protein electrophoresis revealed no paraprotein spike. After this recurrence, the patient received high-dose chemotherapy and underwent autologous stem cell transplant. First described in Walderstrom macroglobulinemia by Drs Dutcher and Fahey in 1959, Dutcher bodies have since been reported in 10–25% of B-cell neoplasms, mainly in plasma cell neoplasms, lymphoplasmacytic lymphoma and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). Electron microscopic studies demonstrated that Dutcher bodies were formed by an invagination of immunoglobulin-rich cytoplasm into the nuclear space (1). In our case, the presence of Dutcher bodies restricted to kappa-lightchain in the large cells not only confirmed the B-cell lineage but also documented the monoclonal nature of the B-cell proliferation.

'Hypopyon' in the anterior chamber: unilateral ocular relapse of acute myeloid leukaemia in a 2-year-old girl.

A 2-year-old girl with acute myeloid leukaemia (AML M5a) with t(8;16)(p11 2;p13 3) who had been in remission since induction chemotherapy presented with lethargy and right eye pain 5 months later. The right eye intraocular pressure was elevated at 45–50 mm/Hg (reference, 10–20 mm/Hg). Anterior segment examination revealed corneal oedema and predominantly circumcorneal injection. The pupil was irregular and reacted to light poorly owing to posterior synechiae; the iris was undulated with overlying fibrinous exudate and a large ‘hypopyon’ in the aqueous (upper left; image taken while the patient was in a supine position). The left eye appeared normal. Cytology of the right anterior chamber fluid showed leukaemic blasts (upper right) with vacuolated cytoplasm and haemophagocytosis (lower left), the features similar to those seen in patient’s initial diagnostic bone marrow examination (lower right). A repeat bone marrow examination demonstrated no evidence of leukaemia, suggesting an isolated ocular relapse. The patient then received an umbilical cord stem cell transplant, but subsequently suffered from graft-versus-host disease and other complications. She expired 2 months after ocular relapse. While isolated ocular relapse of leukaemia has been reported previously, the vast majority of cases are acute lymphoblastic leukaemia rather than myeloid leukaemia. Interestingly, the leukaemic blasts in our case harboured t(8;16)(p11 2;p13 3) that has been associated with monocytic differentiation, haemophagocytosis by leukaemic cells and extramedullary involvement. It remains to be determined if the ocular relapse in this patient was related to the particular cytogenetic change and the leukaemic cells’ unique behaviour (haemophagocytosis). This case emphasizes an inclusion of leukaemic involvement in differential diagnoses for ‘hypopyon’ in the anterior chamber, particularly in a paediatric patient with a clinical history of acute leukaemia, and advocates a cytological examination of the aqueous fluid for a definitive diagnosis.