Donald I. Feinstein

Primary mediastinal lymphoma in adults

The incidence of primary mediastinal lymphoma in adults was investigated in 184 patients with non-Hodgkins lymphoma. This entity was defined as disease within the mediastinum in patients who presented with symptoms due to an enlarging mediastinal mass. Of 184 patients, 17 presented with primary mediastinal lymphoma. All had a diffuse histologic pattern. The most common pathologic type was poorly differentiated lymphocytic lymphoma, diffuse (PDL-D), (11 cases). In nine of these 11 cases the patients had tumors of convoluted lymphocytes. The presentation was rapid in onset, with heart failure, pericarditis, dyspnea and superior vena caval syndrome predominating. Eleven of the 17 were clinical stage I or II, but eight of these had widespread disease on pathologic staging or rapid dissemination soon after diagnosis. In conclusion (1) primary mediastinal lymphoma is always diffuse in histology. (2) The most frequent pathologic type is PDL-D, with convoluted morphology. (3) Compression of vital intra-thoracic structures is common. (4) Although seemingly localized at presentation, this entity usually implies disseminated disease.

Convoluted lymphocytic lymphoma in adults: a clinicopathologic entity.

Twelve adults had a distinct clinicopathologic type of malignant lymphoma that closely resembles the mediastinal lymphomas of childhood. Nine patients presented with mediastinal masses, and seven had symptoms related to intrathoracic compression. Seven patients presented with or developed leukemia, and in four of these patients the central nervous system (CNS) became involved. Structurally, the tumor cells had a distinctive stippled chromatin pattern, in addition to the characteristic nuclear convolutions. Tumor cells from five patients were studied immunologically, and, in each case, the tumor cells formed rosettes with sheep erythrocytes. The response to combination chemotherapy was rapid and dramatic, but usually transient, with relapse in the CNS or previously involved sites. The above data strongly suggest that these cases represent a distinct clinicopathologic entity that should be treated similarly to childhood leukemia and lymphoma, with intensive multiple agent induction, CNS prophylaxis, possibly radiation therapy to initially involved sites, and prolonged maintenance.

Clinical Significance of Accelerated Fibrinolysis in Liver Disease

We compared site and severity of bleeding in 46 patients with cirrhosis of the liver and accelerated fibrinolysis (defined as a dilute whole-blood clot lysis time less than 2 h) to 44 patients with cirrhosis of the liver and normal fibrinolysis (dilute whole-blood clot lysis time greater than 4 h). Patients with accelerated fibrinolysis had a significantly higher incidence of severe soft-tissue bleeding after trauma and a trend toward increased intracranial bleeding. Mucosal, postoperative, and gastrointestinal bleeding were equally frequent in the two groups. The median partial thromboplastin time was significantly longer, and the median bilirubin and fibrin/fibrinogen degradation product levels were significantly higher in the group with accelerated fibrinolysis, but median prothrombin time, platelet count, and levels of fibrinogen and serum albumin were comparable. The fibrinolytic inhibitor epsilon-aminocaproic acid successfully controlled bleeding in 4 of 6 cases used. Accelerated fibrinolysis may predispose patients with cirrhosis to soft-tissue and intracranial bleeding.

Hemophilia A: Polymorphism Detectable by a Factor VIII Antibody

Plasma from 54 patients with hemophilia A was tested for neutralizing activity with a human antibody to factor VIII. The plasma from 52 patients had no demonstrable neutralizing activity. Two plasma samples had neutralizing activity equivalent to that of normal plasma despite the lack of factor VIII clotting activity. Apparently, most patients with hemophilia A do not synthesize factor VIII, whereas a few synthesize an inactive molecule with a presumed genetic structural mutation of the active site but with antigenic determinants in common with normal factor VIII. Thus, hemophilia A is a disease caused by more than a single genetic mechanism.

Factor V anticoagulants: clinical, biochemical, and immunological observations

A patient who had received multiple transfusions for complications of acute hemorrhagic pancreatitis developed a potent factor V anticoagulant with bleeding due to defective hemostasis. Despite its potency, the anticoagulant disappeared within 15 days of its first manifestation. A second patient with adenocarcinoma of the colon developed an anticoagulant to factor V postoperatively after a single blood transfusion. The anticoagulants appeared to react stoichiometrically with factor V in normal plasma in vitro. They had the physicochemical properties of immunoglobulins, and their activity was neutralized by antihuman immunoglobulin antiserum. One anticoagulant appeared to be slightly more active against homologous than against autologous factor V, but it also inhibited heterologous factor V. Both anticoagulants progressively inactivated intrinsic prothrombin activator formed from normal reagents in the incubation mixture of the thromboplastin generation test, thus confirming that factor V is required for the effective action of the intrinsic prothrombin activator. Since the anticoagulants were immunoglobulins whose activity was consumed in their reaction with factor V, consumption of anticoagulant activity was used to detect factor V antigenic material in test materials. Human serum without factor V clotting activity was found to consume anticoagulant activity, i.e., to contain inactive factor V antigenic material. Plasma from two patients with hereditary factor V deficiency (parahemophilia) failed to consume significant anticoagulant activity. Thus, the lack of factor V activity in these patients represents a deficiency of factor V molecules rather than the synthesis of a defective molecule with impaired clotting activity.

Immunoblastic sarcoma: a clinical description.

We reviewed the clinical records of 33 patients with Immunoblastic Sarcoma in order to further describe this disease clinically. Several common features were found. Thirty percent of the patients had a history of a prior immune disease or lymphoproliferative malignancy. Forty‐four percent of the patients tested had a diffuse hypergammaglobulinemia. Lymphopenia (less than 1,000/mm3) was found in 45%, and anemia occurred in 73%. At initial presentation, 30% of the cases were clinically staged as either stage I or II, whereas 70% were found to be stage III or IV. Forty‐nine percent of the patients had systemic symptoms at presentation. The median survival was 14 months. Advanced stage of disease, lymphopenia, and presence of systemic symptomatology were associated with significantly decreased survival times (p <.05). We conclude that IBS is a clinical entity often associated with prior immune disease and/or diffuse hypergammaglobulinemia.

Unresolved issues in laparoscopic splenectomy

BACKGROUND Laparoscopy is now expanding to surgery of intra-abdominal solid organs such as splenectomy for hematologic diseases. The purpose of this study is to further demonstrate that laparoscopic splenectomy is feasible for the surgeon, teachable for the resident, and beneficial to the patient and to revise prior contraindications to this minimally invasive approach. METHODS Thirty-three consecutive cases of laparoscopic splenectomy were performed between May 1992 and March 1996. The series included 21 females and 12 males with a median age of 42 years (range 19-79) and a median weight of 73 kg (range 36-115). Indications included: immune thrombocytopenic purpura (20), hemolytic anemia (5), hereditary spherocytosis (4), infarction with abscess (1), Hodgkins lymphoma (1), Gauchers disease (1), and AIDS-related thrombocytopenia (1). Dissection was predominately performed with a new surgical instrument, the harmonic shears, and main vessels were controlled with clips. RESULTS Thirty-two (97%) of the cases were completed laparoscopically, with 1 (3%) conversion to control hilar bleeding. Four patients underwent simultaneous cholecystectomy. The median spleen size was 13 cm (range 8-28) and median weight was 256 g (range 40-2100). Median operating time was 242 minutes (range 85-515). Morbidity occurred in 2 (6%) patients: ileus and small bowel obstruction. Median hospital stay was 4 days (range 2-14). There was no mortality in our series. Median follow-up was 20 months (range 1-46) with no evidence of late surgical complication or recurrent disease. CONCLUSION Laparoscopic splenectomy may be successful in cases previously considered contraindicated, particularly splenomegaly and splenic infarct with abscess. It is a procedure that can be learned under appropriate guidance in academic centers.

Small noncleaved follicular center cell (FCC) lymphoma: Burkitt and non‐Burkitt variants in the United States. I. Clinical features

With the understanding that Burkitts lymphoma was of follicular center cell (FCC) derivation, Lukes and Collins classified the tumor, descriptively, as small noncleaved FCC lymphoma. Two subtypes were described: Burkitt and non‐Burkitt. Attempting to define the clinicopathologic features of the subtypes, we studied 42 patients: 25 Burkitt and 17 non‐Burkitt. Histologically, the Burkitt tumor demonstrated remarkable uniformity of nuclear size and contour, whereas the non‐Burkitt variant had greater variability. Immunoglobulin monoclonality was demonstrated in 83% of Burkitt and 81% of non‐Burkitt cases. Burkitt patients tended to be younger. Gastrointestinal disease was seen in 15 Burkitt and only four non‐Burkitt patients (P < 0.05). Disseminated disease was found in the majority of both variants. Marrow involvement was demonstrated in 4.5% of Burkitt and 37.5% of non‐Burkitt patients (P < 0.05). Median survival of Burkitt patients was 10.5 months versus 7.7 months in the non‐Burkitt group. The authors believe that significant biologic differences between the variants have been demonstrated, which may be of potential value to the clinician.

Severe Depression of Antithrombin III Associated with Disseminated Intravascular Coagulation in Women with Fatty Liver of Pregnancy

Serial coagulation studies were done in four women with acute fatty liver of pregnancy. All had coagulopathy, laboratory evidence of diffuse intravascular coagulation, and marked depletion of plasma antithrombin III. Two of these women had persistent intravascular coagulation for 4 days after delivery. The others had prompt control of intravascular coagulation coincident with elevation of the antithrombin III concentration by plasma transfusion. Severe antithrombin III depression may be a major cause of the persistent intravascular clotting and can be corrected by plasma transfusion.

Pathology of autoimmune myelofibrosis: A report of three cases and a review of the literature

We identified 3 patients with autoimmune myelofibrosis (AM) lacking American Rheumatism Association criteria for systemic lupus erythematosus (SLE). They had 1 or 2 cytopenias and lacked serologic evidence for SLE. Autoimmune features included psoriatic arthritis and positive direct Coombs test (DCT) result, DCT-positive autoimmune hemolytic anemia, and synovitis with polyclonal hypergammaglobulinemia. Bone marrow biopsy specimens from each patient were evaluated by routine morphologic and immunohistochemical examination. They demonstrated marked hypercellularity (2 cases) or hypocellularity (1 case), moderate erythroid hyperplasia (all cases) with left-shifted maturation (2 cases), intrasinusoidal hematopoiesis (all cases), slightly to moderately increased megakaryocytes (2 cases), and grade 3 to 4 reticulin fibrosis (all cases). All lacked basophilia, eosinophilia, bizarre megakaryocytes, clusters of megakaryocytes, and osteosclerosis. Mild to moderate bone marrow lymphocytosis was noted in all cases. In 2 cases, increased small T cells and B cells formed nonparatrabecular, loose aggregates. AM is a clinicopathologic entity that may lack features of SLE. Loose aggregates of bone marrow T and B lymphocytes and the absence of morphologic and clinical features of myeloproliferative disease or low-grade lymphoproliferative disease are clues that distinguish AM from better known causes of bone marrow fibrosis.