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The spleen can be a troublesome specimen for the surgical pathologist, not only because experience with the range of "normal" splenic histology is limited by its rarity but also because there is an often a frustrating discordance between the patient's clinical condition and the perceived findings. Patients with a dramatic clinical presentation that points to splenic pathology ("hypersplenism" or marked splenomegaly) not infrequently have no discernable or have barely perceptible histologic abnormalities of the spleen. Similarly, patients whose spleens contain histologic findings that seem to deviate significantly from the "norm" (histiocytic proliferations, vasoformative lesions, stromal hyperplasia) may have no clinically detectable hematologic complaints. For most pathologists, the frame of reference for normal splenic histomorphology derives largely from experience with autopsy spleens and spleens removed for trauma or immune thrombocytopenia. These are all settings in which pre-existing disease, the immune status of the patient, and therapy influence the findings and--in cases in which fixation has been delayed--even the ability to make the findings. This review presents practical aspects of splenic development and immunoarchitecture and relates this to the pathologist's approach in evaluating the abnormal spleen and assists in resolving such discordances. Benign conditions that contrast with the subjects of subsequent articles in this issue are emphasized.

Mantle cell lymphoma (MCL), an uncommon and aggressive form of non-Hodgkin lymphoma, typically involves lymph nodes. It usually only secondarily involves extranodal sites. We describe an unusual case of a MCL that presented and relapsed in the earlobes. Light microscopic findings were initially regarded as suggestive of small lymphocytic lymphoma, although subsequent analysis of fresh tissue by flow cytometry led to the diagnosis of MCL. Retrospective application of a broad panel of recently developed markers suitable for analysis of routinely processed tissue yielded results that also permitted a diagnosis of MCL. If these results had been available at the time of initial presentation, they would have obviated the need for rebiopsy. Greater awareness not only of the phenotypic criteria by which lymphomas are classified but of the lymphoma markers available for evaluation of routinely processed tissue should facilitate the accurate diagnosis of diseases like MCL and minimize the risk of misdiagnosis as an indolent disorder.

BACKGROUND Few studies have examined the yield of the diagnostic splenectomy, and the relevance of these studies to the management of patients with unexplained splenomegaly or a splenic mass are limited by low number of cases, the use of selection criteria, and the lack of modern terminology and modern ancillary studies. The current study correlates clinical intent with preoperative clinical and radiologic studies and histologic findings in an assessment of the diagnostic yield of splenectomy. METHODS The medical charts, laboratory data, radiologic studies, and pertinent preoperative biopsies on all patients who underwent splenectomy between the years 1986 and 1995 were reviewed, and the clinical intent behind the procedure was correlated with histologic findings. RESULTS One hundred twenty-two of the 1280 patients underwent splenectomy for diagnosis, and in 116 patients a specific disease was identified histologically that explained the splenomegaly/splenic mass; malignancy was the most common cause of unexplained splenomegaly or splenic mass, though benign neoplasms and reactive disorders were documented in 25% of the cases. Primary splenic lymphomas were most commonly of large cell B-cell type. CONCLUSIONS In the setting of splenomegaly or splenic mass, splenectomy has a high diagnostic yield and usually discloses a malignancy. The clinical category of “primary splenic lymphoma” is biologically heterogeneous, and the diagnosis is usually an intermediate grade (not low grade) lymphoma. The range of conditions associated with splenic masses were quite commonly associated with diseases that are amenable to fine-needle aspiration (FNA) diagnosis, whereas those disorders associated only with splenomegaly included a large fraction of diseases for which FNA may yield either incomplete or misleading results. Cancer 2001;91:2001–9. © 2001 American Cancer Society.

SUMMARYInfection with Helicobacter pylori causes chronic active gastritis, which is characterized by neutrophils infiltrating the gastric epithelial layer and the underlying lamina propria as well as by T, B lymphocytes and macrophages accumulating in the lamina propria. In this study, the chemokine profile responsible for the recruitment of these inflammatory cells is investigated. Using both RNA/RNA in situ hybridization and immunohistochemistry, the expression of the neutrophil and/or lymphocyte-attractant CXC chemokines growth-related oncogene alpha (Groα), IL-8, interferon-gamma (IFN-γ)-inducible protein-10 (IP-10), monokine induced by IFN-γ (MIG) and the CC chemokines macrophage inflammatory protein-1α (MIP-1α), -1β, regulated on activation normal T cell expressed and secreted (RANTES) and monocyte chemoattractant protein-1 (MCP-1) is studied and microanatomically localized in the gastric mucosa. Macrophages in the lamina propria at sites with neutrophil infiltration and gastric epithelium infiltrated by neutrophils highly expressed the neutrophil-attractant chemokines Groα and IL-8. Additionally, Groα and IL-8 were expressed by neutrophils themselves localized within gastric epithelium, in the foveolar lumen and in the cellular debris overlying mucosal erosion. IP-10 and to a lower extent MIG, both selectively chemotactic for inflammatory T cells, were expressed by endothelial cells of gastric mucosal vessels and by mononuclear cells at sites with T cell infiltration. Expression of all other CC chemokines tested was significantly lower. These in vivo data indicate that a set of predominantly CXC chemokines modulates the inflammation in H. pylori gastritis. Groα and IL-8 may play an important role in neutrophil trafficking from the mucosal vessel into the gastric epithelium, whereas IP-10 and MIG contribute to the recruitment of inflammatory T cells into the mucosa.

We examined the patterns of relapse or persistence in 37 cases of nodal peripheral T-cell lymphoma (PTCL) to address the morphologic and immunophenotypic findings. Relapses were documented in lymph node (25 cases) and/or a variety of extranodal sites at a mean of 21 months after presentation; several cases recurred as late as 13 years. Persistent bone marrow involvement was a feature of angioimmunoblastic lymphoma (AIL) and histiocyte-rich and small-cell tumors. Relapses in anaplastic tumors often involved unusual extranodal sites. The majority of relapsed PTCLs retained a similar histologic appearance, pattern of nodal involvement, and immunophenotype. Histologic progression, as assessed by increased numbers of large cells, was seen in 3 cases of AIL, in 1 case with an initial small cell morphologic appearance, and in 2 cases of PTCL with an initial mixed small and large cell appearance. Immunostains for T-cell activation markers showed increased immunoreactive cells in 5 of the 6 cases, whereas increased numbers of p53-positive tumor cells were noted in 3 of the 6 cases. The discrete large cell transformation occasionally seen in B-cell lymphoma and extranodal T-cell lymphoma was not observed in these cases.

Chemokine receptors mediate the migration of lymphocytes through the binding of soluble ligands, and their expression is differentially regulated in lymphocyte subsets. The pattern of chemokine receptor expression in T-cell non-Hodgkin lymphoma has not been previously studied. Using a panel of mouse monoclonal antibodies, we studied the immunohistochemical expression of the Th1-associated chemokine receptor CXCR3 in 141 patients with T-cell lymphoma, and we studied the receptors CCR4 and CCR5 and some of their ligands in a subset of these tumors. Expression of CXCR3 was typical of the smaller T cells in angioimmunoblastic lymphoma (15 of 18 patients), angiocentric lymphoma (3 of 3 patients), histiocyte-rich tumors (4 of 5 patients), and unspecified T-cell lymphomas (17 of 39 patients). CXCR3 expression was seen in only 1 of 15 patients with anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphoma. In contrast, all ALK-positive tumors showed diffuse reactivity for the Th2-associated receptor CCR4 (5 of 5 patients). CCR4 expression was also a consistent feature of the large-cell transformation of mycosis fungoides. CCR5 expression showed no consistent association with any T-cell tumor type. The chemokines Mig (CXCR3 ligand), TARC (CCR4 ligand), and MCP-2 (CCR5 ligand) were detected in intratumoral blood vessels and histiocytes. Mig was also coexpressed by a subset of CXCR3-positive tumor cells in 6 of 20 lymphomas. MCP-2 was highly expressed in stromal cells in 3 patients with nodal involvement by cutaneous T-cell lymphoma. As with normal T-cell subsets, we demonstrated that there is frequent differential expression of chemokine receptors in T-cell tumors, which may explain, in part, the distinctive patterns of spread in different tumor subtypes.

A major cause of morbidity and mortality following lung transplantation is posttransplant lymphoproliferative disease (PTLD). In a retrospective cohort analysis of pediatric patients, we evaluated the risk factors associated with PTLD in 128 first-time lung transplant recipients from 1990 to 1997. The greatest risk factor for PTLD was a diagnosis of cystic fibrosis (CF). Of the 16 patients in our analysis who had PTLD, 13 had a diagnosis of CF (odds ratio [OR]: 5.8; confidence interval 95% [CI]: 1.6 to 21.4). Because of the high frequency of PTLD in patients with CF (13 of 61; 23%), we performed a retrospective cohort analysis in which patients with CF and PTLD were designated as cases and patients with CF and without PTLD served as controls. In patients with CF, the only risk factor associated with PTLD was two or more episodes of acute rejection within 3 mo after transplantation (OR: 11.0; 95% CI: 2.7 to 55.7). Age, recipient Epstein-Barr virus or cytomegalovirus status, induction with antilymphocyte globulin or antithymocyte globulin (ATG), or use of ATG or OKT3 for acute rejection episodes were not risk factors for PTLD. The high frequency of PTLD in the subgroup of patients with two or more episodes of graft rejection within 2 mo after lung transplantation was unexpected, and warrants further investigation in prospective clinical studies and basic laboratories.

Aims To present the clinical light microscopic and immunophenotypic features of a distinctive vascular neoplasm of the spleen. Methods and results Two of the splenic lesions arose in children, and one was found in an adult. They ranged from 19 to 40 mm diameter and histologically were quite similar. Sheets of large epithelioid cells with a spectrum of nuclear configurations ranging from oval and vesicular to twisted and hyperchromatic were noted in each case. Distinct or prominent nucleoli were present in many cells, and occasional cells had nuclear pseudoinclusions. In two cases, bands of basophilic, fibroblast-rich stroma with scattered chronic inflammatory cells were present. The mitotic rate ranged from 0/10 high-power fields (HPF) to 0.5/10 HPF in these epithelioid cells. The vascular nature of these tumours was manifested as a sieve-like array of round, erythrocyte-filled spaces, most with attenuated and cytologically bland lining cells. The polygonal, epithelioid cells exhibited the following phenotype: smooth muscle actin (SMA)+, muscle specific actin (MSA)+, vimentin+, CD31−, CD34−, CD21−, CD8−, CD68− (2/3 cases), S100−, while the lining cells were CD34+, vimentin+ and SMA−, with variable CD31 and factor VIII related antigen expression. Elongated SMA+, MSA+ cell processes were evident in one case, reminiscent of previously characterized myoid elements of the normal spleen. An uneventful follow-up was noted for all three patients. Conclusions The histology and immunophenotype set these neoplasms apart from classic hamartomas, haemangiomas and previously characterized (haem)angioendotheliomas of the spleen, and may represent proliferations of myoid elements native to the spleen.

Some reports have indicated that trisomy 3 represents a characteristic chromosomal abnormality found in lymphomas arising in mucosa-associated lymphoid tissues (MALT)/extranodal marginal zone B-cells (MZBC). Traditional cytogenetic analysis of metaphase preparations is cumbersome and not always possible, especially in those situations in which the diagnosis in not suspected before a biopsy. Our aim is to use a relatively simple method to evaluate trisomy 3 in paraffin-embedded, formalin-fixed tissue, using fluorescence in situ hybridization (FISH) on intact tissue sections. Formalin-fixed, paraffin-embedded archival tissues from 30 cases (27 lymphoma and 3 chronic gastritis cases) were hybridized with a chromosome 3 specific alpha-satellite probe (ONCOR, Gaithersburg, MD). Three of four cases of gastric MZBC/MALT lymphoma revealed trisomy 3. Ten cases of lymphoma of possible or probable MZBC origin were examined, and four revealed trisomy 3. Five of 13 non-MZBC lymphomas revealed trisomy 3. None of the chronic gastritis cases nor normal tonsil cases revealed trisomy 3. Our results, using a different methodological approach, confirm the findings of others that trisomy 3 is an abnormality found in a significant proportion of lymphomas of MZBC origin. Our approach also makes possible interphase cytogenetic analysis (by FISH) of routinely processed formalin-fixed, paraffin-embedded tissues, without the need to disaggregate cells. It thus may facilitate genetic analysis on specimens previously deemed unsuitable for such analysis, particularly when tissue quantity is limited.

Graft versus host disease (GVHD) occurs in up to 75% of patients who have had an allogeneic bone marrow transplant (BMT). However, the pathophysiology of this disorder, including the mechanisms responsible for enhanced apoptosis, are poorly understood. Bcl-2 is a cellular protein known to inhibit apoptosis in a variety of human tissues. Therefore, the aim of this study was to evaluate the expression of Bcl-2 in colonic GVHD and to determine its relationship to cell proliferation and apoptosis in this disease. Routinely processed colonic mucosal biopsy specimens from 47 allogeneic BMT patients with diarrhea were evaluated histologically for the grade of GVHD (0-4) and for the degree of apoptosis (apoptosis index). Immunohistochemical staining for Bcl-2 and MIB-1, a cell proliferation marker, was performed, and the results were correlated with the histological findings and with each other. Normal-appearing colonic mucosal biopsy specimens from 10 age-matched patients with noncolonic diarrhea served as controls. Also evaluated were 13 colonic biopsy specimens from 13 patients with chronic ulcerative colitis (three inactive, four mild chronic-active, six moderately severe chronic active) to test the specificity of our findings. When compared with controls, a slight trend toward increased Bcl-2 expression was noted in patients with high-grade GVHD (grade 3 or 4) (P=.09). However, Bcl-2 expression did not correlate with the degree of apoptosis in these patients. In contrast, the degree of Bcl-2 staining correlated positively with the crypt proliferative rate (P=.04). Furthermore, crypt proliferation was significantly higher in the GVHD patients in comparison with controls (MIB-1 index, 27.7+/-17.1 v 15.6+/-11.4, =.02), and increased progressively with each successively higher grade of GVHD, and with the degree of apoptosis. Similar to GVHD, Bcl-2 expression was increased in biopsy specimens of CUC patients with higher grades of active injury and epithelial regeneration. This immunohistochemical study does not provide support for Bcl-2 in the pathogenesis of GVHD-induced apoptosis in the colon, but instead, indicates that this protein may play a nonspecific role in the generalized response to cellular injury in GVHD.

BACKGROUND An unusual case of a peripheral T-cell lymphoma of T γ/δ hepatosplenic type (Tγ/δHSL) that arose in a child 5 years after she received a heart transplant and 9 months after she developed Epstein-Barr virus (EBV) positive, B-cell lymphoid hyperplasia involving the tonsils is presented. The majority of the reported cases of Tγ/δHSL have been described in young adult men without antecedent immunodeficiency; several well documented cases of Tγ/δHSL in the posttransplant setting have been described previously, but none has been described in a child (or an adult) with a previously diagnosed EBV+ B-cell lymphoid hyperplasia. METHODS Standard histologic, immunohistochemical, flow cytometric, and molecular genetic techniques were used in the evaluation of diagnostic material. RESULTS The patient's Tγ/δHSL involved the spleen in a predominantly cordal pattern, and infiltrated the liver in an exclusively sinusoidal distribution. Bone marrow involvement was focal and interstitial. In all locations, malignant cells were of intermediate or large size and had oval nuclei with coarse chromatin, with a scant or moderate amount of eosinophilic cytoplasm. This Tγ/δHSL expressed the characteristic CD2+, CD3+, [CD4- CD8-], Tδ1+ phenotype, and malignant cells also expressed the natural killer cell marker CD56. Cytogenetic studies demonstrated isochromosome 7q with the addition of trisomy 8 as the tumor progressed. Southern blot analysis demonstrated clonal rearrangements of the γ, δ, and β loci of the T-cell receptor but did not identify EBV DNA within the tumor cells. CONCLUSIONS This case highlights the fact that a full range of lymphoid proliferations is possible in the posttransplantation period, and that a prior diagnosis of a B-cell disorder does not preclude the development of a subsequent T-cell posttransplant lymphoproliferative disorder (PTLD), which should be formally evaluated, especially if clinical circumstances appear atypical for a PTLD of the "usual" (EBV-related, B-cell) type. Cancer 1998;82:983-92. © 1998 American Cancer Society.

The presence of abundant inflammation is uncommon in well-differentiated liposarcomas (WDLPS). We describe ten cases of WDLPS in which an extensive lymphoplasmacytic infiltrate was present to such a degree that the differential diagnoses included inflammatory pseudotumor and Castleman's disease, and in which the lipogenic component could easily be overlooked. The median age (62 years) and tumor location (six retroperitoneal, three head/neck, one paratesticular) was comparable to usual WDLPS, as was the fact that six of ten cases recurred locally, but none metastasized during the period of follow-up (range 13 to 228 months, median 72 months). Key histologic features included (1) nodular lymphoplasmacytic aggregates; (2) intervening paucicellular stroma containing fibroblastic elements, frequently with plasma cell-rich zones and scattered atypical, often multinucleate cells; (3) merging of atypical adipocytic and inflammatory elements; and (4) adjacent clearly defined zones of lipoma-like or, more rarely, sclerosing-type liposarcoma. In recurrences, two cases "reverted" to purely lipoma-like liposarcoma, and two cases dedifferentiated. Immunoperoxidase studies demonstrated that B cells predominated in the lymphoid aggregates, and that the abundant plasma cells were polytypic in nature. We support the use of the term well-differentiated inflammatory liposarcoma for tumors of this type, which should be distinguished from high-grade liposarcoma containing inflammatory cells, and in order to identify a subgroup of WDLPS at high risk for misdiagnosis.

We report 19 unusual cases of mixed tumors and myoepitheliomas arising in soft tissues. The neoplasms occurred in 12 males and seven females. The age at diagnosis ranged from 2 to 83 years (mean 35, median 30). Eight tumors arose in the upper limb, six in the lower limb, three in the trunk, and two in the head and neck region. Three cases involved both dermis and subcutis; the remainder arose in subcutaneous (13 cases) or deep subfascial soft tissue (three cases). The most common presenting complaint was a painless swelling, with duration ranging from 2 weeks to 1 year (median 2.5 months). Microscopically, the tumors were predominantly well circumscribed and lobulated. Six cases showed a focally infiltrative margin. Cardinal morphologic features included nests, cords, and ductules of epithelioid cells and/or nests of spindled cells within a hyalinized to chondromyxoid stroma. One tumor was predominantly composed of myoepithelial cells and devoid of epithelial differentiation (i.e., ductules). Cytoplasmic hyaline inclusions were noted in two cases; squamous differentiation was seen in one case. Osteoid production and/or metaplastic bone was observed in three tumors. Chondroid differentiation (usually mature) was seen in four cases. Adipocytic differentiation was seen in two tumors. Mitotic activity was variable but generally scant; atypical mitotic figures were not identified. By immunohistochemistry, 16 of 16 cases expressed pan-keratin; 16 of 17 S-100 protein; six of 14 alpha smooth muscle actin (IA4); two of 10 muscle specific actin (HHF-35); two of 10 desmin; three of 11 glial fibrillary acidic protein; and three of 16 epithelial membrane antigen. Clinical follow-up was available in 10 patients and ranged from 6 months to 20 years (mean 4.25 years, median 2 years). Two patients developed local recurrence; metastasis to lung and lymph nodes were observed in two additional patients. Both of the latter patients died. We believe that these findings expand the concept of cutaneous mixed tumors to include neoplasms composed predominantly of myoepithelial cells and to include tumors arising in deeper subcutaneous and/or subfascial tissues. The clinical behavior of such neoplasms, when arising in soft tissues, may be difficult to predict but is most often benign; however, a minority of lesions metastasize. Until larger studies with longer follow-up are available, treatment and prognostication are probably best based on criteria used in comparable salivary gland tumors.

This study uses CD10 and epithelial membrane antigen (EMA) as respective proximal and distal tubular segment markers to localize polyoma virus replicative activity, as determined by large T antigen (TAg) expression, in allograft polyoma virus nephropathy (PVN). Sixteen biopsies and 2 nephrectomy specimens with PVN had serial 2-mum paraffin sections stained using monoclonal antibodies to polyoma virus TAg by immunoperoxidase with diaminobenzidine as chromogen. A second immunolabeling step used CD10 as a proximal nephron marker or EMA as a distal tubular marker, and alkaline phosphatase with fast red as chromogen. BK viral DNA was detected in blood in 16 of 18 tested. Fourteen of 16 had cortex and medulla, and 2 had cortex only in the biopsy sample. Fourteen (100%) of 14 had double-positive EMA and TAg expression (EMA+TAg+) in medullary collecting ducts. T antigen was evident in loops of Henle in nephrectomies. Thirteen (81.3%) of 16 had EMA+TAg+, and 10 (62.5%) of 16 had CD10+TAg+ cortical tubular segments. CD10+TAg+ cells were observed in the parietal epithelium of Bowman's capsule in 3 biopsies (18.75%). T antigen was observed in 5.1% of CD10+ tubular profiles compared with 21% of EMA+ profiles in renal cortex (P < .0001). Polyoma virus TAg was observed in medullary collecting ducts, in distal and proximal cortical tubules, and in Bowman's capsule, in decreasing order of frequency. Loops of Henle also had TAg. This distribution suggests potential for an ascending route of infection of allograft tubules in PVN.

The non-Langerhans histiocytoses, a nosologic category to which juvenile xanthogranuoma (JXG) belongs, represent a heterogenous collection of disorders related to the monocyte/macrophage lineage. The dermal dendrocyte was previously proposed as the cell of origin for JXG on the basis of Factor XIIIa reactivity, a suggestion that does not fully explain the occasional xanthogranulomatous proliferations localizing exclusively to extracutaneous sites. This study applies a panel of recently developed immunohistochemical markers to JXGs and relates the phenotype of this process to new concepts of monocyte/dendritic cell ontogeny. Twenty-seven JXG, ten dermatofibromas (DF), and ten age-matched normal skin specimens were stained using standard immunohistochemistry methods, and all JXGs were fascin+ and CD68+, although 26 of 27 were reactive for HLA-DR, 25 of 27 for Factor XIIIa, 25 of 27 for LCA, 21of 27 for CD4, and 8 of 27 for polyclonal s100. Six of those eight polyclonal S100+ cases were also reactive for monoclonal S100. None of those cases was reactive for CD1a, CD3, CD21, CD34, or CD35. Eight of ten dermatofibromas were FXIIIa+; all were negative for HLA-DR, LCA, CD4, and polyclonal s100. In controls, fascin+ dendritic cells were present but did not stain for Factor XIIIa, S100, or CD4. Based on the morphologic and phenotypic overlap of the lesional cells in JXGs and plasmacytoid monocytes, it would appear that the plasmacytoid monocyte might be considered the putative normal counterpart of the major cellular population of JXGs, a proposal that helps explain the extra-cutaneous, visceral, and soft tissue location that have been reported for occasional cases of JXG. We would also conclude that neither Factor XIIIa-nor S100+ results should preclude the diagnosis of JXG, and find that reactivity for CD4 and LCA may be used to distinguish JXG from DF when the latter is heavily lipidized or the former is not.

Purpose: To determine whether the morphologic features of posttransplant lymphoproliferative disease (PTLD) correlated to a response to therapy. Patients and Methods: We reviewed our experience with PTLD in the pediatric population. We identified 32 patients with a total of 36 episodes of PTLD. The diagnosis was confirmed by tissue examination and classified according to the degree of monomorphic features of the lesion. Thirty-four of 36 episodes were managed with immunosuppression reduction, and the patients were assessed for their response to this strategy. Chemotherapy was used to treat 10 of 15 patients who had progressive disease, and their subsequent course was also analyzed. Results: Sixteen of 17 (94%) patients with polymorphic morphology responded to immunosuppression reduction compared with only 5 of 17 (29%) patients with monomorphic features (P < 0.001). All of the patients with progressive disease who did not receive additional therapy died. Standard chemotherapy regimens for lymphoma were administered to 10 patients with progressive disease, with a high response rate (90%), durable remissions, and acceptable toxicity. Conclusions: We conclude that the morphologic characteristics of PTLD provide information to potentially help guide treatment strategies in the management of this disease. Standard chemotherapy regimens for malignant lymphoma appear to be a viable treatment option for patients with progressive disease, although further investigation is needed.

In the pathogenesis of gastric mucosa-associated lymphoid tissue (MALT)-type lymphoma, CagA-positive Helicobacter pylori strains have been suspected of making a significant contribution. To investigate this hypothesis in more detail, the mucosal humoral immune response of 15 patients with gastric MALT-type lymphoma was examined in the tumor and in the tumor-free gastritis of the same patient. Mononuclear cells from different sites (antrum, corpus, lymphoma) were cultured. Culture supernatant and serum of the same patient were used for immunodetection of CagA. All patients displayed an immune response to CagA in the tissue-culture supernatants. Although the humoral immune response in the tumor was restricted to a very few H. pylori antigens, antibodies directed against CagA protein were found in most patients. The immune response to CagA in nearly all lymphoma patients – not only in the serum, but also in the mucosa, including the tumor site – support the hypothesis that CagA is involved in the pathogenesis of gastric MALT-type lymphoma.

This case provides a complete light microscopic, immunophenotypic, and molecular genetic analysis of autoimmune lymphoproliferative syndrome (ALPS), a rare benign cause of dramatic lymphadenopathy with atypical histology and phenotype that may be mistaken for malignancy. The patient is 3-year-old child who was first clinically evaluated at the age of 16 months because of marked generalized lymphadenopathy and hepatosplenomegaly. Histologic sections of a cervical lymph node demonstrated a marked paracortical proliferation of occasional small and intermediate-sized lymphocytes and numerous large immunoblasts, the majority of which displayed a CD3(+), CD43(+), CD45RO(-) (OPD4, UCHL1) CD4(-), CD8(-) phenotype on paraffin sections, and which had a CD2(+), CD3(+), CD5(+), CD56(-), Tdelta1(-), [CD4(-), CD8(-)] double negative profile on flow cytometric analysis. Southern blot analysis did not identify a clonal T or B cell population, and sequencing of the fas gene identified a mutation that caused a single amino acid substitution in the intracytoplasmic death domain of this protein. An enriched population of CD45RO-negative naive T cells in the paracortex may explain the atypical histologic and immunophenotypic features of this case. Greater awareness of this heritable lymphoproliferative disorder will facilitate its recognition and minimize the possibility of misdiagnosis.

We have identified three patients with an initial clinical or biopsy diagnosis of angiokeratoma, all of whom were found to have a more extensive vascular lesion within the surgical excision. A fourth patient with identical histologic findings had no specified clinical diagnosis and his first procedure was excisional. The patients ranged in age from 7 to 16 years, and the lesions were located on the buttock, thigh, calf, and foot. Macroscopic appearances included mildly keratotic pink-red or blue-grey macules (three cases) and pink macules with focal ulceration (one case). In three of the four cases, a shave biopsy diagnosis of angiokeratoma had been made, and the extensive and deeply infiltrative nature of the vascular proliferation was recognized only at subsequent resection, at which point angiomatosis was diagnosed. In the fourth case. excisional biopsy was attempted at presentation, and the superficial morphology was angiokeratoma-like, but the vascular proliferation was present in the deep subcutaneous fat. CD31 and CD34 reactivity was present in the superficial and deep vessels in all cases, and lesional vessels were rimmed by a bland population of smooth muscle actin positive pericytes, findings that differentiate these cases from angiokeratoma, which has previously been reported to be CD34 negative. We conclude that the dilated vascular spaces that typify angiokeratoma may also be seen overlying a deep vasoformative process that is not amenable to resection, and suggest that caution should be exercised in evaluating small biopsies with angiokeratoma-like appearance.

Primary lymphoma of bone has characteristic clinical and radiologic manifestations; however, its histologic features and clinical outcome show considerable variability. The histologic and immunophenotypic features of 13 adult patients with lymphoma as a solitary bone lesion were compared with clinical outcome. All tumors studied were non-Hodgkin lymphoma of anaplastic or large cell type and included B-cell (9 cases), T-cell (3 cases), and null cell (1 case) phenotypes. All patients responded well initially to systemic chemotherapy (with or without radiotherapy); however, disease in 6 patients progressed or recurred, and 5 patients died of disease. Local disease progression was seen in 2 patients, with 4 patients experiencing relapse at distant sites. Expression of CD30, present in 7 cases, was associated with an anaplastic or large noncleaved histologic appearance. Absence of CD30 expression characterized 6 cases, including 4 with multilobate or cleaved morphologic features. Five of 6 cases that recurred were associated with CD30 expression, including 3 with anaplastic features. The 4 tumors with cleaved or multilobate nuclear morphologic features were associated with long disease-free survivals and may represent a distinct lymphoma subtype with a good prognosis.

The Wiskott-Aldrich syndrome (WAS) is a X-linked hematologic disorder characterized by thrombocytopenia, eczema, and immunodeficiency of variable severity. Reported here are the results of a morphologic, morphometric, and immunophenotypic analysis of splenic lymphoid tissue in 12 WAS patients with documented molecular defect and with different disease severity. Spleens from 29 age-matched patients with different diseases were used as controls. Paraffin-embedded tissue (from all cases) and fresh-frozen samples (from 5 WAS patients and 4 control subjects) were used to study the different white pulp compartments by classic morphologic, immunophenotyping, and image analysis techniques. Data were statistically analyzed by both parametric and nonparametric tests. Spleens from WAS patients showed a significant depletion of the total white pulp (p = 0.0008), T cell (p < 0.05), and B cell (p = 0.0002) areas and marginal zone (MZ) thickness (p < 0.0001). Among WAS patients, a negative correlation was found between the score of severity of the disease and all variables considered (Spearman's rank correlation coefficient, r = -0.79, r = -0.73, r = -0.68, and r = -0.56, respectively). In conclusion, this study shows that in WAS a general depletion of the splenic white pulp occurs, supporting the evidence that WAS is characterized by a combined immune defect. The significant reduction of the MZ may explain the inability of WAS patients to mount a response to T-independent antigens.

PURPOSE The patterns of presentation, histologic pattern (nodular or diffuse), treatment, and long-term outcome were studied in patients with lymphocyte-predominant (LP) Hodgkin's disease (HD) to determine whether these patients should be treated differently than patients with other subtypes of HD. PATIENTS AND METHODS Pathology was reviewed for 97 patients with an initial diagnosis of LPHD made between 1970 and 1993. Seventy-five patients had LPHD on review: 55 had nodular LPHD, 14 had diffuse LPHD, and six had LP histology without subclassification. There were 60 males (80%) and 15 females (20%). Sixty-six patients (88%), presented with clinical stage (CS) I or II disease. Seventy-one patients were treated at the Joint Center for Radiation Therapy (JCRT) and were considered for analysis of treatment outcome. Sixty-one of these 71 were treated with radiation (RT) alone; 17 received mantle RT alone, 27 mantle and paraaortic RT, and seven total-nodal irradiation (TNI). Ten patients with subdiaphragmatic HD received pelvic and paraaortic RT. Of the 10 remaining patients, four were treated with RT and chemotherapy (CT) and six were treated with CT alone. The median follow-up time was 10.8 years. RESULTS The 10-year actuarial freedom-from-first-relapse (FFR) and 10-year overall survival rates for the 71 patients with LPHD treated at the JCRT were 80% and 93%, respectively. The 10-year actuarial FFR by nodular (n = 51), diffuse (n = 14), and unspecified (n = 6) histologic pattern was 74%, 100%, and 60%, respectively. Overall, 14 of 71 patients have relapsed: nine of 61 with stage IA, IB, or IIA disease and five of 10 with stage IIB to IVB disease have relapsed. The median time to relapse was 53 months. Nine of 71 patients have died. Only one death has been from HD: five patients died of second cancers, two of cardiac disease, and one of alcoholic liver cirrhosis. Of seven patients with second malignancies, five died. None of the second malignancies were non-Hodgkin's lymphoma (NHL). CONCLUSION Patients with LPHD have different patterns of presentation, sex and age distribution, and likelihood of occult abdominal disease than patients with nodular-sclerosing (NS) or mixed-cellularity (MC) disease. The median time to relapse for LP patients was later than reported for other histologic subtypes; however, there was no pattern of continuous late relapse. With pathologic staging and standard treatment, mortality from LPHD is low; nearly all deaths have been cardiac- or second tumor-related. This suggests that less aggressive treatment for LPHD might continue to yield excellent results, while perhaps lowering the long-term risk of complications.

As cutaneous pilar leiomyomas have received little attention in the recent literature, 53 lesions from 45 patients were studied to analyze their clinicopathologic features. There was an equal distribution between both sexes; most patients were adults with a wide age distribution. Both multiple (29 lesions from 21 patients) and solitary tumors (18 patients) were included. Lesions on the extremity (29 tumors) were common in both groups, whereas truncal tumors (11) were confined largely to patients with multiple lesions. In six patients the number of lesions was not specified. The tumors were painful in 17 patients. Three patients had a positive family history of similar lesions. Histologic study revealed ill-defined bundles of well-differentiated smooth muscle cells in the reticular dermis in all cases, although nine lesions had a more nodular pattern. Overlying epidermal hyperplasia was noted in 29 cases (54.7%). Immunohistochemically there appeared to be an increased number of nerve fibers within and surrounding the tumors. Mitotic activity was observed in 15 lesions (28.3%), 13 of which had

Posttransplant lymphoproliferative disorder (PTLD) occurs in solid organ transplant patients. Recent efforts have led to a classification system with a primary morphologic basis, polymorphic versus monomorphic group (lymphoma and Hodgkin's disease). To test the hypothesis that patients with polymorphic morphology are more likely to respond to a reduction in immunosuppression, we recently reviewed the records of 30 pediatric solid organ transplant patients with PTLD (12 lung, 8 liver, 5 heart, 5 kidney).