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Background: Fibromatosis or desmoid tumor is a rare soft tissue tumor that lacks a metastatic potential, but is characterized by a locally aggressive and infiltrating growth pattern and a high propensity toward local recurrence if incompletely excised., Case Presentation: We report a patient with three post-surgical recurrences of fibromatosis of the breast over a seven year period. The fibromatosis was found to be involving the chest wall musculature and causing persistent and worsening pain. An aggressive operative strategy was undertaken, consisting of mastectomy with en bloc resection of the underlying chest wall musculature, ribs, and parietal pleura., Conclusion: Aggressive surgical management of fibromatosis of the breast with suspected chest wall involvement is appropriate to attempt to obtain a long-term durable cure.

Posttransplantation lymphoproliferative disorder (PTLD) is a life-threatening Epstein-Barr virus (EBV)-associated B-cell malignancy occurring in 1% to 2% of renal transplantation patients. Host- and PTLD-related factors determining the likelihood of tumor response following reduction of immune suppression (IS) and antiviral therapy remain largely unknown. Standard therapy for PTLD is not well established. Eleven consecutive renal transplantation patients who developed EBV-positive PTLD 8 to 94 months after allografting were uniformly treated with acyclovir and IS reduction. All PTLDs were EBV-positive diffuse large B-cell lymphomas. Ten patients (91%) obtained a durable complete response (CR), and 9 (82%) have remained in continuous CR with a median follow-up of 29 months. Five patients (45%) lost their allograft. Of these, 4 patients had PTLD affecting the transplanted kidney. Peripheral blood CD8(+) T cells increased significantly (P =.0078) from baseline in 8 responders available for analysis. One of 2 patients whose absolute CD8(+) T-cell count subsequently dropped to baseline after IS reduction relapsed. The expanded CD8(+) T cells from 2 responders specifically recognized an immunodominant peptide from the EBV lytic gene BZLF-1. Another lytic EBV gene, thymidine kinase, was expressed in all 8 PTLDs tested. IS reduction and antiviral therapy for PTLD after renal transplantation is a highly successful therapeutic combination, but the risk of graft rejection is significant, particularly in patients with PTLD involving the renal allograft. A sustained expansion of CD8(+) T cells and a cellular immune response to EBV lytic antigens may be important for PTLD clearance in renal transplantation patients.

Extranodal Hodgkin disease presenting as a primary localized neoplasm is uncommon, with rare case reports describing primary sites other than lymph nodes. The gastrointestinal tract is the most frequent site of involvement by extranodal Hodgkin disease, typically involving the stomach or small bowel. To date, we have been able to find only one fully documented case of Hodgkin disease of the sigmoid colon confirmed by immunohistochemical studies. We report a case of extranodal Hodgkin disease involving the transverse colon, presenting as inflammatory bowel disease and documented by light microscopic, immunohistochemical, cytogenetic, and molecular studies.

Although the etiology of attention-deficit/hyperactivity disorder (ADHD) is likely multifactorial, family, adoption, and twin studies suggest that genetic factors contribute significantly. Polymorphisms of the dopamine 4 receptor (DRD4) affect receptor binding, and one allele with seven tandem repeats in exon 3 (DRD4*7R) has been associated with ADHD. We examined this putative association in 41 children with severe ADHD and 56 healthy controls who were group matched for ethnicity and sex. The frequency of the DRD4*7R allele did not vary by diagnosis (0.220 vs 0.205 in patients and controls, respectively). Behavioral and brain anatomic MRI measures, previously found to discriminate patients from controls, did not differ significantly between subjects having and those lacking a DRD4*7R allele. These data do not support the reported association between DRD4*7R and the behavioral or brain morphometric phenotype associated with ADHD.

Posttransplantation lymphoproliferative disorder occurs in 1.5% to 13% of heart transplant recipients and rarely involves the allograft. We report a case of posttransplantation lymphoproliferative disorder restricted to the mitral valve in a heart transplant recipient. Thirteen cases of cardiac allograft involvement by posttransplantation lymphoproliferative disorder are reported in the literature. None are restricted to the allograft. Five specify sites of cardiac involvement. Valvular masses without infection necessitate evaluation for posttransplantation lymphoproliferative disorder involvement of the cardiac allograft valve.

Central dopaminergic activity has been assumed to play a role in the efficacy of stimulant drugs in attention deficit/hyperactivity disorder (ADHD), although supporting evidence has been scant. This study examined baseline cerebrospinal fluid (CSF) of boys with ADHD in relation to response to three different stimulant drugs. Forty five boys with DSM-III-R-diagnosed ADHD had a lumbar puncture before double-blind trials of methylphenidate, dextroamphetamine, and placebo. Sixteen also received pemoline as part of a subsequent open trial. Stepwise linear regressions determined significant predictors of drug response. Our prior report of a positive significant correlation between CSF homovanillic acid (HVA) and ratings of hyperactivity on placebo was replicated in a new sample of 20 boys. After baseline symptom severity, CSF HVA was the best predictor of stimulant drug response, with significant independent contribution to four of the ten measures of hyperactivity that changed significantly with medication. Higher HVA predicted better drug response, and lower HVA was associated with worsening on some measures. This supports the mediating role of central dopaminergic activity in stimulant drug efficacy in childhood hyperactivity.

The Kell blood group is a major antigenic system in human erythrocytes. Kell antigens reside on a 93-kDa membrane glycoprotein that is surface-exposed and associated with the underlying cytoskeleton. We isolated tryptic peptides and, based on the amino acid sequence of one of the peptides and by using the PCR, prepared a specific oligonucleotide to screen a lambda gt10 human bone-marrow cDNA library. Four clones were isolated, one containing cDNA with an open reading frame for an 83-kDa protein. All known Kell amino acid sequences were present in the deduced sequence; moreover, rabbit antibody to a 30-amino acid peptide, prepared from this sequence, reacted on an immunoblot with authentic Kell protein. The Kell cDNA sequence predicts a 732-amino acid protein. Hydropathy analysis indicates a single membrane-spanning region, suggesting that Kell protein is oriented with 47 of its N-terminal amino acids in the cell cytoplasm, and a 665-amino acid segment, which contains six possible N-glycosylation sites, is located extracellularly. Computer-based search showed that Kell has structural and sequence homology to a family of zinc metalloglycoproteins with neutral endopeptidase activity.

Diffuse angiomatosis of the extremities is a rare condition characterized by extensive or multifocal benign mass-forming vascular lesions involving multiple tissue planes; histologically, adipose and fibrous tissue are admixed with vascular elements that vary from capillary proliferations to large vessels that are often structurally abnormal. Although diffuse angiomatosis most likely represents a hamartomatous form of arteriovenous malformation, it behaves clinically as a benign but slowly progressive and unresectable neoplasm. We describe a case of diffuse angiomatosis of the lower extremity that presented clinically as a soft-tissue sarcoma.

Recognition and application of blood group differences on human red cells permitted the development of safe procedures for blood transfusion. Blood group antigens are markers on surface-exposed red cell proteins or the sugar moiety of glycoproteins or glycolipids. Apart from their presumed biological function, some antigens have been identified as receptors for host/parasite interactions. Thus, carbohydrates that determine P antigenicity are the binding receptor for certain strains of pyelonephritic coliforms. Other pathogenic coliforms bind to the membrane structure that carries the Dra antigen. A structure associated with Duffy antigens is the attachment receptor for the parasite of Plasmodium vivax malaria, while Plasmodium falciparum parasites bind to structures associated with membrane glycophorins. Structure/function relationships have been established by the finding that lack of Rh protein in red cells of Rhnull phenotype is associated with stomatocytic cell morphology and a hemolytic state. Absence of glycophorin C, and the Gerbich blood group antigens that it carries, is associated with elliptocytic red cells. Absence of Kx antigen protein in the Kell system is associated with the McLeod blood group phenotype, with acanthocytic cell morphology and reduced in vivo survival. McLeod individuals also have late-onset muscular dystrophy and neurological disorders.

Hyperreactio luteinalis (HL) refers to moderate to marked cystic enlargement of the ovaries due to multiple benign theca lutein cysts and is most often associated with hydatidiform mole or choriocarcinoma. The cause of this condition is unknown, but is believed to be related to elevated levels of, or abnormal ovarian response to, human chorionic and pituitary gonadotropins. Only 47 cases of HL unassociated with trophoblastic disease have been previously reported in the English-language literature, mostly before 1974, and almost exclusively in the gynecologic literature. We present two additional cases of HL unassociated with trophoblastic disease and review the literature. One of our case reports documents the unusual occurrence of unilateral HL. Of the 49 cases described, 11 occurred with fetal hydrops (8 immunologic; 3 non-immunologic), 8 with multiple pregnancies, and 30 in otherwise normal single pregnancies. Hyperreaction luteinalis is most often bilateral and found incidentally at the time of cesarean section. However, HL may present during any trimester as an abdominal mass or acute abdomen. The natural course is postpartum regression. Recognition of HL is important, since misinterpretation at laparotomy or erroneous histologic diagnoses have resulted in unnecessary surgery, often with sterilization in 16 of the cases. A conservative approach is indicated with wedge biopsy and frozen section diagnosis. Oophorectomy is necessary only to remove infarcted tissue or to control hemorrhage.

Monospecific Kell blood group antibodies, of either human alloimmune or mouse monoclonal origin, react with a single surface-exposed protein of 93,000 daltons. Chymotryptic peptide maps of the 93,000-dalton protein isolated by antibodies of two different specificities (anti-K7 or anti-K14) indicate that Kell epitopes reside on the same protein. Kell protein is similar in size to band 3 protein but differs markedly in its tryptic and chymotryptic peptide maps, indicating that they are different proteins. In addition, sheep antibody to human band 3 does not react with Kell protein. Rabbit antibody to Kell protein reacts, by Western immunoblotting, with membrane proteins from Kell antigen positive red blood cells but not from those of a Ko (Kell null) cell. In intact red cells only a small portion of the Kell protein is available to lactoperoxidase-catalyzed iodination. Under nonreducing conditions Kell antigen is isolated not only as a 93,000-dalton protein but also as larger protein complexes ranging in size from above 200,000 to 115,000 daltons. Treatment of red cells with iodoacetamide, prior to isolation of Kell protein, reduces the amount of the very large complexes, but Kell protein occurs both as 115,000- and 93,000-dalton proteins.

Absence of KX antigen and of normal expression of the Kell system antigens is associated with bizarre red blood cell morphology when observed by either light or scanning electron microscopy. Numerous acanthocytes and dacryocytes have been observed in the peripheral blood smear of an apparently healthy individual with McLeod-phenotype blood, in a male patient with type II chronic granulomatous disease who had a shortened 51Cr red blood cell survival time, and in a minor population of the red blood cells of his carrier mother.

Since the initial description in 1967, the clinical and laboratory features of Kawasaki's disease (KD) have been well documented. We studied a patient with KD who recovered from the acute phase of the disease, but who subsequently died at home from coronary arteritis. We describe this patient because of bone marrow and lymph node findings that have previously received little attention in the English-language literature.

A murine monoclonal antibody, named anti-Fy6, which agglutinates all human red cells except those of Fy(a-b) phenotype was used for purification and characterization of Duffy antigens. Duffy antigens are multimeric red cell membrane proteins composed of different subunits of which only one, designated pD protein, reacts in immunoblots with the murine monoclonal antibody anti-Fy6. Affinity-purified detergent-soluble antigen-antibody complex obtained from red cells, surface-labeled with 125I yielded a complex pattern of bands when separated by polyacrylamide gel electrophoresis. Proteins that react with anti-Fy6 in immunoblots are: pA and pB (greater than 100 kDa) and pD (36-46 kDa). Electroeluted pD protein aggregates and generates bands of similar molecular mass to pA and pB proteins. Electroeluted pA and pB proteins disaggregate yielding pD protein. Oligomers and monomers of pD protein are present in red cells carrying Duffy antigens and absent in Fy(a-b-) cells. Six other proteins of molecular weight ranging from 68 to 21 kDa either associate or co-purify with pD protein. These proteins are only present in Duffy antigen positive cells. The pD protein is different in Fy(a+b-) and Fy(a-b+) cells by fingerprint analysis. Human antisera identify the same proteins in red cell carrying Duffy antigens as the murine monoclonal antibody anti-Fy6.

The Kell blood group has 18 associated red cell antigens. One, named KX, is the product of an X-linked gene and appears to be a precursor in the Kell biosynthetic pathway. Lack of KX on red cells, caused by inheritance of a variant allele at the X-linked locus, results in gross changes in Kell antigenicity, an effect called the McLeod phenotype. Such cells also show striking morphologic changes. Normal phagocytic leukocytes lack Kell antigens but have strong KX. The leukocytes of boys with X-linked chronic granulomatous disease lack KX antigen and have defective bactericidal function. The fundamental defect in chronic granulomatous disease appears to be failure to inherit the X-linked gene that determines KX synthesis. The enzymatic and functional disorders of the leukocytes, and the structural changes in the red cells, are consequences that follow.

Sinus histiocytosis with massive lymphadenopathy (SHML) was originally defined as a relatively specific benign pseudolymphomatous disorder. Although the etiology remains unknown, the spectrum of SHML has been expanded to include predominance of extranodal disease in some patients, clinically significant immunologic abnormalities in 10% of patients, and fatal outcome in 7% of patients. We report the rare occurrence of SHML in identical twins; to our knowledge, SHML in identical twins has been reported only once previously. The two patients described are also unusual because of the predominance of retroperitoneal disease with minimal peripheral adenopathy. After a seven-year clinical course, one twin died of extensive retroperitoneal disease, liver failure, bleeding diathesis, and seizure disorder. The other twin is alive after a six-year course of progressive retroperitoneal disease.

The McLeod phenotype is an X-linked, recessive disorder in which the red blood cells demonstrate acanthocytic morphology and weakened antigenicity in the Kell blood group system. The phenotype is associated with a reduction of in vivo red cell survival, but the permanent hemolytic state is usually compensated by erythropoietic hyperplasia. The McLeod phenotype is accompanied by either a subclinical myopathy and elevated creatine kinase (CK) or X-linked chronic granulomatous disease (CGD). Seven males with the McLeod red-blood-cell phenotype and associated myopathy but not CGD, one male with the McLeod phenotype associated with CGD, and two males known to possess large deletions of the Duchenne muscular dystrophy (DMD) locus were studied. DNA isolated from each patient was screened for the presence or absence of various cloned sequences located in the Xp21 region of the human X chromosome. Two of the seven males who have only the McLeod phenotype and are cousins exhibit deletions for four Xp21 cloned fragments but are not deleted for any portion of either the CGD or the DMD loci. Comparison of the cloned segments absent from these two McLeod cousins with those absent from the two DMD boys and the CGD/McLeod patient leads to the submapping of various cloned DNA segments within the Xp21 region. The results place the locus for the McLeod phenotype within a 500-kb interval distal from the CGD locus toward the DMD locus.

Recent immigrants from Southeast Asia were screened for hematologic abnormalities using a multichannel cell counter (Coulter S), peripheral smear, free erythrocyte protoporphyrin (FEP), isoelectric focusing, and a qualitative screen for glucose-6-phosphate dehydrogenase deficiency. Hematologic abnormalities were further defined by hemoglobin electrophoresis, globin electrophoresis, HbA2 levels, and HbF levels. Of the 189 adults studied, 68 (36 percent) were hematologically abnormal, including 28 hemoglobin E (HbE) heterozygotes, six HbE homozygotes, 14 with alpha-thalassemia minor, and 10 with presumptive iron deficiency. Of the 54 people with microcytic (MCV less than 80fl) red blood cells (RBC), 52 had evidence of HbE or thalassemia and two had iron deficiency alone; five had both iron deficiency and a hemoglobinopathy. Homozygosity for HbE results in an asymptomatic condition similar to thalassemia minor with microcytic RBC, large numbers of target cells, normal or slightly reduced hematocrit and greater than 90 percent HbE. People heterozygous for HbE are asymptomatic and have hematologic findings similar to thalassemia minor with slightly reduced or low normal MCV and 25 to 35 percent HbE.

Staging laparotomy was performed at the University of Virginia Medical Center on 111 patients with Hodgkin's disease. The operation included multiple liver and lymph node biopsies and, excepting three patients, splenectomy. The histopathology was reviewed and the 111 patients were classified as follows: nodular sclerosis, 74; mixed cellularity, 28; lymphocyte predominance, 7; and undetermined, 2. There were no deaths. Wound, pulmonary or urinary tract complications occurred in 11 patients. One case of postoperative thrombophlebitis occurred and in another case small bowel obstruction developed, and resolved without reoperation. The pathologic stage (PS) following laparotomy was unchanged from the clinical stage (CS) in 64%, reduced in 20%, and advanced in 16%. The therapy, however, was altered in 38% of the patients. Lymphangiography in 103 patients was interpreted as showing lymph node involvement in 38, equivocal involvement in 11, and no involvement in 54. Among the 92 examinations reported as either positive or negative, 77% were confirmed histopathologically, 21% were falsely positive, and 2% were falsely negative. The spleen was positive for Hodgkin's disease in 39% of cases, and in these patients with positive spleens there was no reason to suspect intra-abdominal involvement preoperatively in 21%.

Congenital dysgranulopietic neutropenia (CDN) is a recently proposed entity that describes a small subgroup of children with clinically severe neutropenia. We followed and studied a 3-year-old girl with neutropenia (less than 500/mm3) and recurrent severe infections in whom repeated marrow evaluations revealed large (30-50 microns) multinucleated promyelocytes to polymorphonuclear cells with as many as 4 to 16 nuclei or nuclear lobes, respectively. In addition to the nuclear endoreduplication, ultrastructural and cytochemical evaluation of these cells demonstrated abnormalities in granule genesis and centriole structure. Concomitantly, immunoperoxidase staining indicated that many of the granules were devoid of lactoferrin but not lysozyme. In vitro proliferation studies revealed normal to increased thymidine labeling, normal numbers of colony-forming cells, and normal colony-stimulating activity from blood and marrow mononuclear cells, findings consistent with ineffective myelopoiesis. However, serum folate, B12, and lysozyme levels were normal. The nuclear and cytoplasmic abnormalities in this patient result in an extreme example of CDN, distinct from previously described cases.

Rh-negative erythrocytes were found in the blood of an Rh-positive man suffering from myelofibrosis. Nucleated hemopoietic precursors were also circulating in his blood, and these cells had an abnormal chromosome complement from which identifiable chromosome segments had been deleted. Correlation of the serological and cytogenetic findings, combined with previous data, indicates that the Rhesus blood group locus is on the distal portion of the short arm of chromosome No. 1.

Approximately one in 250 people with autoimmunity involving their red cells have IgG autoantibodies with specificity in the Kell blood groups. Red cells of these individuals have an acquired temporary weakening of their Kell antigens. Some of the patients also have allo-anti-K in their serum. This report presents a case in which an IgG autoantibody may define a new high-incidence red cell antigen related to the Kell blood groups. The patient's Kell blood group antigens are depressed, and his serum contains allo-anti-K. It is postulated that reduced red cell Kell antigenicity is caused by enzymatic degradation, possibly of bacterial origin, and that the acquired loss of Kell antigens, the Kell-specific autoimmune state, and the serum all0-anti-K, are all related aspects of one phenomenon.

Female genital tract involvement is a rare manifestation of disseminated coccidioidomycosis; to our knowledge, only ten patients have previously been described in the English literature. We describe a patient who seems to be unique in that she developed female genital tract coccidioidomycosis and coccidioidal peritonitis after chemotherapy for Hodgkin's disease. Coccidioidomycosis of the female genital tract is usually manifest as granulomatous endometritis and/or granulomatous tubo-ovarian disease with peritonitis. The diagnosis of coccidioidomycosis was unsuspected clinically in all 11 reported cases (including our patient); initial diagnosis was made by biopsy or culture in all 11 patients. In eight of the reported cases of female genital tract coccidioidomycosis (including our patient), clinical improvement occurred after treatment with surgery or antifungal chemotherapy; three patients died of disseminated coccidioidomycosis.

Blood group genes are inherited in a straightforward manner and their products are readily detectable. Because of this they are utilized over a wide area of scientific endeavor and provide excellent markers for use in gene mapping of the human chromosomes. Both the Rh and Duffy blood group genes have now been localized to the number 1 chromosome. Studies of a patient whose red cells exhibit mosaicism for the Rh blood group indicate that loss of the end of the short arm of chromosome number 1 is associated with loss of an Rh gene complex. The Rh gene can, therefore, be assigned with some precision to this region of the chromosome.

Benign cartilage-containing mesenchymal tumors of the breast are extremely rare. We describe a patient with chondrolipoma of the breast who presented with a breast mass that was detected by routine mammography. Although the mammographic features of chondrolipoma are not specific, the histologic features are diagnostic and show a well-circumscribed mass composed of benign adipose tissue and lobules of mature cartilage. We also discuss the differential diagnosis of benign mesenchymal tumors of the breast.

A partially purified blood group-like substance obtained from milk showed I activity with 2 of 21 anti-I sera. With these antisera, certain human ovarian cyst substances considered to be precursors of the A, B, H, Le(a), and Le(b) substances also showed I activity comparable to the milk material. Strong I activity could be produced by one-stage periodate oxidation and Smith degradation of human ovarian cyst A and B substances, or of hog mucin A + H substance, or by mild acid hydrolysis of human saliva or ovarian cyst blood group B substance. The two sera indicate that I specificity appears at intermediate stages in the biosynthesis of the A, B, H, Le(a), and Le(a) substances. Anti-I sera differ strikingly in their specificities, indicating substantial heterogeneity of the I determinants.

The laboratory findings on a blood donor whose blood coagulation time was greatly prolonged are described. The defect was caused by a deficiency of Hageman (contact) factor, the nature of the defect being demonstrated by a simple glass adsorption test using normal serum.