The serglycin proteoglycan is best known as a hematopoietic cell granule proteoglycan. It has been found that serglycin is synthesized by endothelial cells, is localized to cytoplasmic vesicles, and is constitutively secreted. Serglycin messenger RNA in human umbilical vein endothelial cells (HUVECs) and cultured human aortic endothelial cells was detected by reverse transcription-polymerase chain reaction. 35 Ssulfate-labeled secreted and intracellular proteoglycans were analyzed. It was found that 85% of the proteoglycans synthesized during culture were secreted. A core protein of the appropriate size for serglycin was detected by analysis of the chondroitinase-digested 35 Ssulfate-labeled HUVEC proteoglycans. This was the major core protein of the secreted chondroitin sulfate proteoglycans. Recombinant serglycin core protein was used to generate an antibody in chickens. A core protein identified by Western blotting of chondroitinase digests of HUVEC proteoglycans corresponded to the major 35 IntroductionThe serglycin proteoglycan was initially discovered as a secretory and membrane-associated product of rat L2 yolk sac tumor cells, 1 and its core protein was the first proteoglycan gene to be cloned. 2 L2 cells are thought to originate from parietal endoderm. 3 Over a number of years, it was found that several types of hematopoietic cells in several species synthesize a proteoglycan with a very small core protein and a characteristic resistance to trypsin digestion. [4][5][6][7][8][9][10] The proteoglycan core protein was purified from human platelets, 11 and its amino acid sequence and the complementary DNAs (cDNAs), which were cloned from human 12-14 and murine 15 hematopoietic cells, were found to be highly homologous to the rat L2 serglycin core protein. Messenger RNA (mRNA) for serglycin was subsequently identified in most blood and bone marrowderived cells by Northern blotting or in situ hybridization. 10,[16][17][18][19][20][21] Serglycin has thus come to be known as the hematopoietic proteoglycan. The serglycin proteoglycan is distinguished by the S/G (single-letter amino acid codes) repeat region in the central portion of the molecule, which is the site of attachment of the glycosaminoglycan (GAG) chains and gives the molecule its unique structural characteristics. The proteoglycan has either heparin or chondroitin sulfate GAGs, or it can be a hybrid of chondroitin sulfate and heparan sulfate chains, depending upon the cell source. [19][20][21] The function of the serglycin proteoglycan is not known, but it is likely that it is involved in packaging of proteins into secretory granules and/or directing the secretion of such molecules as cytokines or chymases. 22 These modes of regulation might reflect the interactions of the proteoglycan with other granule constituents or could involve osmotic effects that are due to the extensive hydration of the GAG chains. Serglycin is stored in granules for secretion upon activation by some cells and is secreted constitutively by others; in some cases, both mechan...

Follicular lymphomas with plasmacytic differentiation were described more than two decades ago. However, the possibility that some of these reported cases are marginal zone lymphomas or composite lymphomas must be considered. In addition, it is also uncertain whether follicular lymphomas with plasmacytic differentiation have any unique cytogenetic or other features. Therefore, fluorescence immunophenotypic and interphase cytogenetic analysis of 14 well-characterized follicular lymphomas with plasmacytic differentiation was performed using a CD138 antibody to identify the plasma cells and with BCL2, BCL6, IGH@ and MALT1 breakapart probes and a chromosome 12 centromeric probe. CD10 was expressed in 12/14 cases, BCL6 in 12/12 cases and BCL2 in 12/14 cases. At least one cytogenetic abnormality was identified in 12/14 cases. The same abnormality was present in both the plasmacytic (CD138 þ ) and non-plasmacytic (CD138À) component in all 10 evaluable cases. BCL2 rearrangements were present in seven cases (5 IGH@ rearranged, 1 IGH@-not rearranged, 1 IGH@-not evaluable), BCL6 rearrangement in two (1 also with BCL2/IGH@ rearrangement), þ 12 in 1, þ MALT1 without þ 18 in 1, IGH@ rearrangement without other abnormalities in 1 and IGH@ rearranged or partially deleted in 1 case. No cases showed þ BCL6 (3q27) or a MALT1 rearrangement. All six cases with an isolated BCL2 rearrangement had predominantly interfollicular plasmacytic cells whereas, 6/7 cases without the translocation had concentrations of intrafollicular or perifollicular plasmacytic cells (Po0.005), as did the case with BCL2 and BCL6 translocations. These results support the existence of bona fide follicular lymphomas with plasmacytic differentiation and support the clonal relationship of the neoplastic lymphoid and plasma cells in at least most of these cases. The differential distribution of the plasma cells, specifically in relation to the presence or absence of an isolated BCL2 rearrangement suggests that the latter cases may be distinctive, sharing some features with marginal zone lymphomas.

The normal counterparts of mantle cell lymphoma (MCL) are naïve quiescent B-cells that have not been processed through the germinal center (GC). For this reason, while lymphomas arising from GC or post-GC B-cells often exhibit plasmacytic differentiation, MCL rarely presents with plasmacytic features. Seven cases of MCL with a monotypic plasma cell (PC) population were collected from six centers and studied by immunohistochemistry, FICTION (Fluorescence immunophenotyping and Interphase Cytogenetics as a Tool for the Investigation of Neoplasms), capillary gel electrophoresis, and restriction fragment length polymorphism of immunoglobulin heavy chain analysis (RFLP/IgH) of microdissections of each of the MCL and PC populations to assess their clonal relationship. Clinical presentation was rather unusual compared to typical MCL, with two cases arising from extranodal soft-tissues of the head. All MCL cases were morphologically and immunohistochemically typical, bearing the t(11;14)(q13;q32). In all cases PC populations were clonal. In 5 of the 7 cases, the MCL and PC clones showed identical restriction fragments, indicating a common clonal origin of the neoplastic populations. The two cases with clonal diversity denoted the coexistence of two different tumors in a composite lymphoma/plasma cell neoplasm. Our findings suggest that MCL can present with a PC component that is often clonally related to the lymphoma, representing a rare but unique biological variant of this tumor.

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A 53-year-old man presented with acute, severe loss of vision in both eyes. Three days earlier, he had noticed a painless deterioration of his vision, which had progressed until he could no longer read a newspaper using either eye. On examination, the patient's best corrected visual acuity was 20/100 using both eyes. He had full visual fields by confrontation and the motility of extraocular muscles was normal. No afferent pupillary defect was evident. Examination of the posterior segment showed bilateral edema in the optic nerve head with multiple cotton wool spots and areas of retinal whitening (Purtscher flecken) (Figure 1). Intravenous fluroescein angiography showed severe ischemia of the nasal macular retinal arterioles with extensive secondary late leakage. Based on these findings, we diagnosed Purtscher disease or Purtscher-like angiopathic retinopathy.Pertinent laboratory findings included an elevated erythrocyte sedimentation rate of 83 (normal 0-20) mm/hr, elevated total protein of 92 (normal 60-80) g/L and a serum IgG immunoglobulin of 41.8 (normal 7-17) g/L. These results prompted a skeletal survey that showed small lytic lesions in the proximal humerus, skull and proximal femur. Serum protein electrophoresis showed a monoclonal M spike of 3.39 g, which was eventually determined by immunofixation to be IgG/Kappa type. His peak serum viscosity was elevated at 2.3 (normal 1.4-1.8) centipoises. A bone marrow biopsy was then performed and showed large aggregates of plasma cells comprising approximately 33% of the cell mass. Immunohistochemical stains showed that the plasma cells were kappa light-chain restricted, which was consistent with multiple myeloma, and involved about 70% of the marrow cellularity.Our patient presented with the classic appearance of Purtscher-like retinopathy as an initial manifestation of multiple myeloma. We considered the possibility that hyperviscosity from multiple myeloma was playing a role in our patient's visual loss. Symptoms of hyperviscosity usually appear when a normal serum viscosity climbs to 4-5 centipoises, which often corresponds to a serum IgG level of 40 g/L.1 The patient was treated with three cycles of plasmapheresis, resulting in a drop in the viscosity to a baseline of 1.3 centipoises. He was also given dexamethasone and lenalidomide. After eight months, his vision had improved to 20/400 (right eye) and 20/30 (left eye).Purtscher's retinopathy is rare and most commonly seen after trauma, acute pancreatitis, crush-type injury, long-bone fracture, orthopedic surgery and childbirth.2 Acute retinal signs often persist for at least one month after the initial injury and include Purtscher flecken, cotton wool spots and retinal hemorrhage.2 Spontaneous visual recovery of at least two Snellen lines occurs in half of patients.