Aggregates Of Small Lymphocytes Research Articles

The Rare First Manifestation Of Mantle Cell Lymphoma As Immune Complex Glomerulonephritis With Crescents And Membranoproliferative Features

Abstract Introduction/Objective Initial presentation of Non-Hodgkin Lymphoma (NHL) with immune complex glomerulonephritis (ICGN) is rare. Mantle cell lymphoma (MCL) is a rare aggressive lymphoma comprising 3–7 % of all NHL and ICGN as the first manifestation of MCL is very unusual. Methods We report a 73 year-old-man with increased serum creatinine (2.1 mg/dl) from normal baseline 3 months ago. Urinalysis showed the presence of dysmorphic RBCs, RBC casts and 300 mg/dl of protein. Physical examination revealed diffuse lymphadenopathy. Hepatitis C and B Ab, HIV screen, ANA, ANCA, Anti dsDNA Ab, Anti GBM Ab, and Serum protein electrophoresis were normal or negative. Results The renal biopsy showed Immune complex glomerulonephritis with (25%) fibrocellular/cellular crescents and focal membranoproliferative (MPGN) features. There were foci of dense monomorphic lymphoid aggregates of small lymphocytes and 30% interstitial fibrosis with corresponding tubular atrophy. No tubulitis was present. Direct Immunofluorescence showed 2+ to 4+ granular mesangial and capillary loop staining for Total Ig, IgG, IgA, IgM, C1q, C3 and C4. The lymphoid aggregate was monoclonal Kappa. Electron microscopy showed widespread podocyte foot process effacement, subendothelial and rare mesangial dense deposits. Excisional lymph node biopsy flow cytometry showed a monoclonal population of CD19+, CD20+, CD22+, CD5+, skappa-restricted, CD10-, CD11c-, CD23-, CD25- CD38-, CD103-, CD200- B- cells. Cyclin D1 was positive on immunostain, consistent with stage IV (renal) MCL. He received chemotherapy with steroids, bendamustine, and rituximab leading to resolution of lymphadenopathy and proteinuria and improvement in serum creatinine. Conclusion It is important to recognize that the first manifestation of MCL may present as renal involvement in the form of ICGN and, as in this case, with fibrocellular/cellular crescents and a focal MPGN pattern. This is an extremely rare, but important, cause of renal insufficiency that can be successfully treated with lymphoma chemotherapy.

Keloid-like morphoea

Conflict of interest: none declared. An 11‐year‐old Bangladeshi girl presented with a 1‐year history of a hyperpigmented patchy eruption involving her arms, neck, trunk and proximal thighs. The linear plaques over her lower abdomen were slightly sclerotic and more infiltrative (Fig. 1). Her previous medical history was unremarkable, with achievement of normal developmental milestones and completed immunizations. Laboratory investigations showed that the patient was mildly positive for rheumatoid factor (titre of 1 : 40), but negative for antinuclear and anticentromere antibodies. Renal and liver function tests, iron studies, thyroid profile, full blood count, and tests for human immunodeficiency virus and human T‐lymphotropic virus were normal or negative. Magnetic resonance imaging scams of the pelvis, abdomen and chest were unremarkable, and tissue T‐cell rearrangement studies did not identify any monoclonal T‐cell expansion. On histological examination of initial biopsy samples taken from the upper arm and abdomen, dense, thickened dermal collagen fibres were seen throughout the upper dermis, extending into the lower dermis. There were small aggregates of lymphocytes and plasma cells around the deeper dermal vessels. There were no granulomas or histiocytic cell infiltrates. Stains for fungi, parasites and acid‐fast bacilli were all negative.

An Unusual Case of Cutaneous Blastic Plasmacytoid Dendritic Cell Neoplasm With Concomitant B-Cell Lymphoproliferative Disorder

Blastic plasmacytoid dendritic cell neoplasm is a rare hematologic malignancy characterized by aggressive clinical behavior and frequent cutaneous involvement. We describe a case of a 64-year-old man with a rapidly enlarging subcutaneous forearm mass. Histologic examination of the excisional biopsy specimen revealed a diffuse proliferation of atypical hematolymphoid cells in the dermis extending to the deep subcutaneous soft tissues. Occasional aggregates of small lymphocytes were noted to be distributed within the mass. The tumor cells expressed CD4, CD45, CD56, CD123, and terminal deoxynucleotidyl transferase (TdT) but not CD3, CD20, or CD34. A diagnosis of blastic plasmacytoid dendritic cell neoplasm was rendered. Chromosome analysis revealed a 45 X, -Y karyotype. In addition, flow cytometry identified a small population of monoclonal B cells. A staging bone marrow aspirate and biopsy was performed, which showed normal cytogenetics and no evidence of involvement by blastic plasmacytoid dendritic cell neoplasm. Flow cytometric evaluation of the bone marrow revealed a CD5-negative, CD10-negative monoclonal B-cell population consistent with a B-cell lymphoproliferative disorder. This is a very unusual example of cutaneous blastic plasmacytoid dendritic cell neoplasm with a novel cytogenetic finding and concomitant B-cell lymphoproliferative disorder. Although previously not reported, our case shows that blastic plasmacytoid dendritic cell neoplasm may be associated with lymphoid malignancy. The relationship between the 2 neoplasms, however, is unclear. A high degree of suspicion and bone marrow examination in patients with a new diagnosis of blastic plasmacytoid dendritic cell neoplasm is required to avoid this potential diagnostic pitfall.

Rare presentation of in situ mantle cell lymphoma.

e18566 Background: Mantle cell lymphoma (MCL) is an aggressive, rare (<10%) B cell neoplasm that is triggered by a tl(11;14)(q13;32) leading to an upregulation of cyclin D1. This cancer is generally considered to be incurable with a median survival of approximately four years. the malignant lymphoma cells most often present in four different patterns: diffuse, nodular, expanded mantle zone or the blastic variant. Two prior case reports have reported in situ MCL. In these cases, patients were treated aggressively with differing outcomes. One relapsed one year after presentation with generalized disease including bone marrow involvement, the other remained in remission. Methods: Case report. Results: This patient presented with asymptomatic right inguinal adenopathy Excisional biopsy of one of the nodes revealed a few scattered small aggregates of small lymphocytes having CD5 positivity. They also stained positive for CD20, CD79a, bcl2 and cyclin d1. The benign germinal centres were negative for the lateral...

Incidental chronic lymphocytic leukaemia in a biopsy of Merkel cell carcinoma

Chronic lymphocytic leukaemia (CLL) shows cutaneous involvement in 2% of cases. Merkel cell carcinoma (MCC) is a rare primary cutaneous epithelial neoplasm most commonly found in sun-exposed sites in elderly male Caucasians. A 66-year-old man presented with a 2-month history of a purple painless 2 cm tumor on the scalp. Excision biopsy revealed an incompletely excised MCC, and at the periphery of the MCC, a lymphocytic infiltrate interpreted as reactive. A re-excision biopsy showed residual MCC as well as dense aggregates of small lymphocytes within and surrounding the MCC. Immunohistochemistry showed characteristic dot-like cytoplasmic positivity for cytokeratin 20 in the MCC; the lymphocytic infiltrate was positive for CD5, CD20 and CD23, diagnostic of CLL. Subsequent staging revealed widespread lymphadenopathy, and lymph node biopsy showed CLL. Histologically, CLL and MCC are 'round blue cell tumors' and are therefore in the differential diagnoses of each other. Whenever there is a more prominent than expected infiltrate of small lymphocytes surrounding a skin lesion in an elderly patient, immunohistochemistry to rule out CLL is advised. This case adds to the literature suggesting an increased incidence of CLL and other neoplasms in patients with MCC and vice versa.

Osseous lesions resembling vaccine-site sar comas in two cats

Extract Lytic lesions with microscopic features similar to those of vaccine-site sarcomas were diagnosed in the distal femur of two young neutered male cats, one a 20-month-old Birman and the other an 18-month-old domestic short-hair (DSH). Radiographically, there was extensive destruction of trabecular and cortical bone in the metaphysis and/or epiphysis of the distal femur. The DSH cat also had angular deformity of the distal femur due to asymmetrical involvement of the physis. Histologically, the lesions in both cats consisted of dense, interwoven bundles of fibrous connective tissue, amongst which there were variable numbers of plump malignant mesenchymal cells, often with very large, hyperchromatic nuclei and irregularly shaped nucleoli. Several focal aggregates of small lymphocytes were present in both tumours. Although neither cat had apparently been vaccinated in the hindlimb it is possible that the tumours had been triggered by injection of some other irritant material.

Tissue changes adjacent to titanium plates in patients

Introduction: Titanium miniplates are widely used for osteosynthesis in maxillofacial surgery. Titanium is considered to be well tolerated but the long-term effects of titanium retained within human tissues are unclear. Aims: This study was designed to evaluate histomorphologically the soft tissues adjacent to titanium maxillofacial miniplates and screws in patients, and to determine the nature of pigmented, particulate debris found in the tissues. Materials: Thirty-five soft tissue specimens were excised from the tissues adjacent to titanium miniplates which had been in situ for between 1 month and 13 years. Methods: All of the soft tissue specimens were prepared for examination under the light microscope. Four specimens were examined under the scanning electron microscope and the transmission electron microscope. Energy dispersive X-ray analysis (EDX) was used to confirm the elemental composition of the particles under investigation. Results: All of the soft tissues showed fibrosis. Pigmented debris was present in 70% of the specimens and titanium was identified by EDX analysis. The debris was predominantly extra-cellular and was not associated with any inflammatory response or giant cell reaction. Fibroblasts were the predominant cell with small aggregates of lymphocytes and scattered macrophages. Conclusion: Titanium is apparently well tolerated for up to 13 years.

Invasion of the brain and chronic central nervous system infection after systemic Mycobacterium avium complex infection in mice.

Central nervous system (CNS) infections caused by nontuberculous mycobacteria have been described previously, especially in patients with AIDS. To investigate specific aspects of the pathogenesis of this entity, C57BL bg(+)/bg(-) mice were infected intravenously with Mycobacterium avium, and cultures of blood and brain as well as histopathology examination of brain tissue were carried out at several time points up to 6 months after infection. Low-grade inflammatory changes with small aggregates of lymphocytes and macrophages as well as perivascular cuffing were seen early in the infection. A small number of bacteria could be observed in the parenchyma of the choroid plexus. Six months after infection, numerous bacteria were present within the foamy macrophage of the granulomatous lesions along the ventricle and meninges. None of the mice developed clinical signs of meningitis or encephalitis or even died spontaneously during the period of observation. Use of CD18(-/-) knockout mice indicated that transport of the bacterium within neutrophils or monocytes into the brain is unlikely. Mild chronic CNS infection developed in the mice during sustained systemic M. avium infection, similar to what has been reported in most human cases.

Neurohistopathological findings after continuous intrathecal administration of morphine or a morphine/bupivacaine mixture in cancer pain patients.

As the number of terminal cancer patients receiving continuous intrathecal infusion of opioids and local anesthetics for relief of pain increases, we decided to investigate the post-mortem findings of the spinal cord, meninges and nerve roots of patients after continuous intrathecal administration of morphine and combined with bupivacaine. Neurohistopathological findings were obtained from 10 cancer patients [2 men and 8 women, 29-69 (median 52) yrs old] and 4 controls [4 men, 46-75 (median 64) yrs old]. The cancer patients had been treated for a mean of 98 (range 8-452) d with morphine/NaCl 0.9% or morphine/bupivacaine, administered through a polyamide lumbar catheter. Concomitant radiation therapy and chemotherapeutic drugs had been given to 5 and 6 patients, respectively. Cumulative doses of morphine ranged from 22 to 3895 mg, those of bupivacaine from 0 to 3250 mg and of sodium metabisulfite (antioxidant) from 0.6 to 97.4 mg. No macroscopic abnormalities of the catheter tract, dura, leptomeninges, nerve roots or spinal cord were found. Microscopically, focal foreign body giant cells were seen in 2 cases in the area of the catheter pathway both without any sign of inflammation. In one case treated for 103 d, an intrathecal reaction was found. This consisted of small aggregates of lymphocytes predominantly in the leptomeninges and focally in the cord parenchyma. No abnormalities were found in the other cases when using hematoxylin-eosin and Kluver or Bodian stained specimens, indicating neither myelin nor axonal damage. Microglial reactions were similar in both cancer patients and controls. The discrete and limited neurohistopathological findings in both catheter patients and controls suggest that intrathecal infusion of morphine and bupivacaine via a polyamide catheter is devoid of significant neurotoxic effects in cancer patients.

Metal particles and tissue changes adjacent to miniplates. A retrieval study.

Peri-implant soft tissue and bone from 12 patients undergoing removal of stainless steel miniplates and screws after healing of jaw fractures were studied with regard to histomorphology and metal content. Three patients with titanium plates were also included. Light microscopy and scanning electron microscopy with energy-dispersive X-ray microanalysis were used. Non-osseous tissue adjacent to devices of both materials showed fibrosis, including areas of mild chronic inflammation. The cellular picture was dominated by fibroblasts with small aggregates of lymphocytes and scattered macrophages. A connective tissue collar was found between the bone tissue and the screws of both stainless steel and titanium. Bone formation was also evident adjacent to screws of both materials. Stainless steel or titanium particles 5-50 microns in diameter were found in both soft tissue and bone next to implants of their corresponding bulk material. The amount of metal impregnation varied between individual sections, and fewer particles were found in the bone specimens than in soft tissue. The mild inflammatory changes were not restricted to areas of metal impregnation.

Role of Helicobacter felis in chronic canine gastritis.

Five gnotobiotic Beagle dogs were orally inoculated with a pure culture of Helicobacter felis. The remaining two littermates served as contact controls. Thirty days after infection, all animals were euthanatized and specimens were collected for evaluation. In infected dogs, H. felis was recovered from all areas of the stomach. Colonization was heaviest in the fundus and antrum. H. felis was not cultured from any segment of the gastrointestinal tract distal to the duodenum. Two weeks after infection, all five infected dogs had detectable IgM and IgG serum antibody to H. felis, whereas control dogs had no measurable H. felis serum antibody throughout the study. Histopathologic changes in the stomachs of infected dogs included large numbers of lymphoid nodules throughout all regions of the gastric mucosa and were most numerous in the fundus and body. A mild, diffuse lymphocytic infiltrate with small numbers of plasma cells and eosinophils was also present in the subglandular region of all portions of the gastric mucosa. Electron microscopic examination revealed large numbers of spiral-shaped H. felis in gastric mucus adjacent to or superimposed over the areas of inflammation. Occasionally, however, H. felis was observed within the canaliculi of gastric parietal cells. Histopathologic changes in the stomachs of the contact control dogs were limited to focal infiltrates of eosinophils and small aggregates of lymphocytes in the subglandular portions of the gastric mucosa in one animal. Infection with H. felis is a likely cause of naturally occurring lymphofollicular gastritis.

ELEVEN AND TWO-THIRDS YEARS' SURVIVAL AFTER CANINE ORTHOTOPIC LIVER TRANSPLANTATIO,N1

The first animal to survive chronically after orthotopic liver transplantation was a mongrel dog that received a hepatic homograft on March 23, 1964. The recipient was estimated to be 2 years old. The unrelated mongrel donor was of a different color and appearance. Immunosuppression was with azathioprine which was stopped after 120 days. Treatment was never resumed. The transplanted liver was biopsied on several occasions during the next 5 years and was always thought to be normal (2, 4). After a brief illness, the dog died on the night of December 8, 1975, at the estimated age of 14 years and after a total survival post-transplantation of 11 years and 8½ months. He had appeared to be well clinically until 1 or 2 days before death. For most of the post-transplant period, the dog had normal liver function tests (Fig. 1). However, during the last 12 months of life, there was intermittent transaminasemia and elevation of the serum alkaline phosphatase. A few weeks before death, the serum bilirubin was increased to 2.5 mg/100 ml. FIGURE 1 Serum biochemistries during the 11 years and 8½ months of survival following orthotopic liver transplantation on March 23, 1964. The values recorded during the last 8 months of life represent individual determinations. All other points on the ... At autopsy, the liver was of normal size. It weighed 2.7% of the body weight, which was 12.5 kg. The liver had a nutmeg appearance and was hard. There were no abnormal venous collaterals suggestive of portal hypertension. The reconstructed vena cava above and below the liver and the portal vein were normal, with barely detectable sites of anastomosis. To arterialize the liver, a segment of donor aorta in continuity with the hepatic artery had been anastomosed to the infrarenal recipient aorta. Although the hepatic artery was grossly normal, the homograft aorta had extensive calcified atherosclerosis. Biliary reconstruction was with cholecystoduodenostomy after ligation of the distal common duct. The gallbladder, the common duct, and all the intrahepatic ducts were filled with small or medium-sized stones or else with a soft, variably colored green to orange sludge. The stone analysis showed predominantly bilirubin with only trace amounts of cholesterol and bile salts. Other significant findings at autopsy were pulmonary edema, coronary artery disease, and left ventricular hypertrophy. The immediate cause of death was congestive heart failure. Histopathological evaluation of the homograft revealed portal fibrosis and linking of the enlarged portal tracts to one another by connective tissue septa (Fig. 2). There was concentric scarring around the interlobular and septal bile ducts and proliferation of ductules at the margins of the portal tracts. Many of the larger bile ducts were dilated and filled with inspissated bile. The epithelium of the affected ducts was ulcerated and there were aggregates of small lymphocytes, plasma cells, and macrophages around the ducts. A few bile “thrombi” were present in the centrilobular part of the bile canaliculi. Liver cell damage was slight. The arteries and arterioles were normal. These changes are typical of chronic large duct biliary obstruction. There was no evidence of rejection. FIGURE 2 Canine hepatic homograft at autopsy 11 years and 8½ months after transplantation. Fibrous septa link enlarged portal tracts (arrows). There is proliferation of bile ductules and concentric scarring and mononuclear cell infiltration around the ... The thymus, mesenteric and mediastinal lymph nodes, and Peyer’s patches appeared to be normal. The spleen had been removed at the time of transplantation. Examination of the rest of the tissues confirmed the narrowing of the coronary arteries by atherosclerosis, the hypertrophied left ventricle, and the congestion and edema of the lungs. The atherosclerosis in the homograft aorta was severe, with large patches of calcification and bone formation with marrow. By contrast the recipient aorta was normal. The kidneys were normal. Thus, although the dog died primarily of cardiovascular manifestations of old age, a potentially lethal biliary duct complication was present which would have independently caused death within a short time. A partial obstruction of the cystic duct was apparently the main cause of the extensive stone and sludge formation that had affected both the extrahepatic and intrahepatic ducts. The intrahepatic biliary plugging with inspissated bile casts was similar to a syndrome that we (1, 3) and Waldram et al. (5) have noted in humans. Such findings in animals and man point again to the reconstructed biliary duct system as the Achilles’ heel of liver transplantation. The completely normal findings in this dog’s lymphoid system were of interest, since no immunosuppression whatever had been given for 11½ years.