Concanavalin A-binding histiocytes in Hodgkin's disease. A predictor of early relapse

Staining with Concanavalin agglutinin (Con A) reveals a far greater number of macrophage-histiocytes (M-H) in paraffin sections than any other staining method. With Con A staining, the shapes of stromal M-H are clearly visualized, thus enabling a study of their morphologic variations. Con A staining patterns were also unchanged in specimens left at room temperature for 24 to 28 hours before fixation. The appearance of Con A-binding histiocytes was studied in tumors, recurrent as well as original, of 18 patients with biopsy-proven early relapse (within 26 months of diagnosis), and compared with those of 26 patients who were in complete remission (lasting 48 months at the minimum). The early-relapse patients were diagnosed from 1977 through 1984, and all received intensive combination chemotherapy. The relapse-free patients were treated in various manners, and included six patients diagnosed in the 1960s who were treated with radiation alone. Three forms of Con A-binding histiocytes were easily recognized: medium-sized cells similar to those seen in reactive follicles, characterized by uniform nuclei and distinct, abundant cytoplasm (Type A); cells of varying size and shape with altered cytoplasm, rarefied and ragged with indistinct cell borders, or globular (Type B); and large cells, stellate or spindling (Type C). Large numbers of Type A cells were present in all tumors of the relapse-free patients but were virtually absent in the original and recurrent tumors of the early-relapse group. Conversely, Type B cells were rare in the relapse-free group, but were the most common type in the patients with early relapse. Type C cells were not seen in the former group, but were present in the latter. These observations suggest that the morphologic variations of Con A-binding histiocytes in Hodgkin's disease are associated with tumor behavior. Con A staining, which can best depict stromal histiocytes in paraffin sections, may be used to identify patients at a high risk of early relapse.     

Hodgkin's disease in AIDS complex patients. Report of four cases and tissue immunologic marker studies

Hodgkin's disease developed in four homosexual men with prodromal manifestations associated with the Acquired Immune Deficiency Syndrome (AIDS) (generalized lymphadenopathy in three and persistent diarrhea, fever, and weight loss in one). All had inversion of the peripheral blood helper-to-suppressor T-cell ratio. The presentations with Hodgkin's disease were atypical with advanced disease (Stage IIIB or IV) in three of four patients and marrow involvement at diagnosis in two. Response to therapy was poor. Immunopathologic studies on the Hodgkin's disease tissue were performed in two patients. In contrast to Hodgkin's disease in non-AIDS risk patients, the Hodgkin's disease tissue in these patients demonstrated severe depletion of helper T-lymphocytes with a predominance of suppressor cells (tissue helper-to-suppressor cell ratio of 0.19 and 0.33, respectively, on immunoperoxidase-stained preparations). In contrast, in five cases of Hodgkin's disease from non-AIDS risk individuals, the lymphocytes population consisted predominantly of helper T-lymphocytes (median tissue helper-to-suppressor cell ratio 3.15, range 2.12-7.77). Homosexual men with AIDS risk factors are at risk for the development of Hodgkin's disease. Hodgkin's disease in these patients may be atypical with severe depletion of helper T-lymphocytes and a predominance of suppressor cells. The lack of an appropriate T-cell immunologic response may contribute to the poor prognosis observed in these patients.     

Bone Marrow Findings in Malignant Histiocytosis and/or Malignant Lymphoma with Concurrent Hemophagocytic Syndrome

We examined bone marrow specimens from 19 patients with malignant histiocytosis (MH) and/or malignant lymphoma (ML) with concurrent hemophagocytic syndrome (HS) who suffered from high fever, hepatosplenomegaly, liver dysfunction, profound cytopenia, and erythrophagocytosis. There was little lymph-node enlargement or no tumor formation. The neoplastic cells in 3 patients exhibited histiocytes/macrophages phenotype with positive reactions for fluoride-sensitive nonspecific esterase, lysozyme and CD68 (KP1). Twelve other patients showed a T-cell (CD3) phenotype, in which 5 patients expressed CD30 (BerH2) as well. B-cell characteristics with CD20 (L26), CIg. νλ and γκ were manifest in 2 patients, but indeterminate markers were found in the 2 remaining patients. Eighteen patients showed an infiltration of large neoplastic cells mainly with noncohesive interstitial growth pattern, ranging from 1.7% to 74.2% of the nucleated cells in the bone marrow. A large number of histiocytes/macrophages and dendritic cells was diffusely observed in 15 patients. Severely decreased hematopoiesis in all three series of hematopoietic cells was found in 16 patients.

Bone marrow infiltration by the neoplastic cells and numerous reactive cells with erythrophagocytosis appears be an important factor of profound cytopenia in patients of MH and/ or ML with HS. The infiltrating pattern of the neoplastic and reactive cells in the bone marrow of MH and/or ML with HS was different from that of other types of peripheral T-cell ML, B-cell ML in high grade malignancy, and Hodgkin's disease. Cell characteristics and lineage of the neoplastic cells in MH and/or ML with HS are also discussed in this study.     

Primary gastrointestinal lymphomas: a classification of 66 cases.

Using routine histology, resin embedded sections and immunohistochemical techniques on formalin-fixed, paraffin processed tissue, 66 cases of primary gastrointestinal lymphoma have been classified. This study necessitated the development of reliable criteria to separate lymphomas of true histiocytic origin from those of lymphocytic origin. Among the morphologic properties of malignant histiocytes were complex pleomorphic nuclei, abundant well delineated cytoplasm and phagocytosis. These cells were shown to contain all major immunoglobulin chains, C3, lysozyme and in some cases alpha 1 antitrypsin. Malignant lymphomas derived from histiocytes could be divided into two groups: malignant histiocytosis of the intestine (MHI), a recently described diffuse pleomorphic lymphoma associated with villous atrophy of the small intestine, and histiocytic lymphoma (HL) which forms solid tumor masses in a similar manner to lymphocyte derived tumors. Immunohistochemical studies of lymphocyte derived tumors were negative apart from one case with plasmacytoid differentiation. Of the 66 cases, 50% were of histiocytic origin (33% MHI, 17% HL) and 41% of lymphocyte origin, there was one case of Hodgkin's disease and five cases were unclassified. The role of the histiocyte in gastrointestinal mucosa deserves further study.     

The localization of Hodgkin's disease in lymph nodes. A study with immunohistological, enzyme histochemical and rosetting techniques on frozen sections.

Lymphoid tissue of 51 patients with Hodgkin's disease was studied with immunohistological, enzyme histochemical and rosetting techniques for the detection of B and T cells in frozen sections. In lymph nodes of patients with lymphocyte predominance type of Hodgkin's disease, the majority of the lymphocytes in the involved areas were normal B lymphocytes of polyclonal origin. This was also true for nodular sclerosis cases with a predominance of lymphocytes. Surrounding Sternberg-Reed cells small clusters of T lymphocytes could be demonstrated. In mixed cellularity and also in nodular sclerosis with a mixed cellular pattern only small residual areas of B lymphocytes were present, whereas relatively large numbers of T lymphocytes were found in the involved areas. In lymphocyte depletion B lymphocytes were scarce and T lymphocytes were present in small number. It is concluded that different patterns of lymphocyte population can be discerned in the subtypes of Hodgkin's disease. A predominance of B lymphocytes is found in cases with lymphocyte predominance and thus is a prognostic favourable sign. A predominance of T lymphocytes as found in cases with a mixed cellular pattern with or without nodular sclerosis is therefore not a favourable sign in general but may indicate progressive disease. The possible reasons for the presence of large numbers of B or T lymphocytes in lymphoid tissue affected by Hodgkin's disease are discussed.     

Anti-interleukin-1 reactive cells in Hodgkin's disease

Constitutional symptoms (or B-symptoms) of Hodgkin's disease may be mediated by interleukin 1 (IL-1), a product of macrophage-histiocytes. To further study this relation, the authors examined the cells that reacted with anti-human IL-1 antibody in biopsy specimens from 140 untreated patients with Hodgkin's disease (72 asymptomatic patients and 68 with B-symptoms). Fever was the most common symptom, present in 57 of the 68 patients. Anti-IL-1 reactive cells were observed in 62 cases. A positive staining reaction was observed in three types of cells: Reed-Sternberg and related (R-S) cells (33 cases); small to medium cells of undetermined origin (18); and granulocytes (11). The staining was negative in 78 cases, including 42 with B-symptoms. The majority of tumors (27/33) with positively stained R-S cells were from asymptomatic patients. Most tumors (14/18) with positively stained small to medium sized cells were from patients with B-symptoms. Large numbers of granulocytes were positively stained in five asymptomatic patients and six with B-symptoms. The immunohistochemical demonstration of IL-1-bearing cells in tumors does not correlate with the manifestation of constitutional symptoms in Hodgkin's disease.     

Tonsillar Lesions of Infectious Mononucleosis Resembling MALT Type Lymphoma. A Report of Two Cases

Infectious mononucleosis (IM) is an acute lymphoproliferative disorder that typically occurs in young patients and is usually caused by Epstein–Barr virus. We report here, two cases of tonsillar lesion of IM resembling marginal zone B-cell lymphoma mucosa-associated lymphoid tissue (MALT) type. The patients consisted of an 18-year-old Japanese woman and a 36-year-old Japanese man. Both patients presented with tonsillar mass. Histologically, in one case, the tonsil showed diffuse proliferation of medium-sized lymphocytes. The medium-sized lymphocytes had round or slightly indented nuclei with a small solitary nucleoli and abundant clear cytoplasm and somewhat resembled monocytoid B-cells. In the remaining one case, the lymphoid follicles had hyperplastic germinal centers with ill-defined borders surrounded by a sheet-like proliferation of polymorphous infiltration showing a marginal zone distribution pattern. On high-power field, the interfollicular area was diffusely infiltrated by a polymorphous infiltrate of medium-sized lymphocytes with angulated nuclei somewhat resembling centrocyte-like cells, immunoblasts, plasma cells, plasmacytoid cells and histiocytes with or without epithelioid cell feature. However, there were no CD43+ B-cells in either lesion. Moreover, the polytypic nature of the B-cells was demonstrated by immunohistochemistry or polymerase chain reaction. Although MALT type lymphoma rarely affected young adults, notably, a number of cases have been reported in the tonsil. The present two cases indicated that acute IM should be added to the differential diagnosis for MALT type lymphoma in young adults.     

Fever Characteristics and Impact on Safety and Efficacy of Chimeric Antigen Receptor T-Cell Therapy

BackgroundFever is a hallmark symptom of cytokine release syndrome (CRS) after chimeric antigen receptor (CAR) T-cell therapy. Fever characteristics and the impact of fever on safety and efficacy post CAR T are not well understood. We sought to explore the impact of fever and its characteristics on safety and efficacy post CAR T-cell therapy.Patients and MethodsWe reviewed 40 patients with various hematologic malignancies (non-Hodgkin lymphoma, acute lymphoblastic leukemia, multiple myeloma) treated with CAR T-cell therapy between March 2019 and March 2022. We evaluated all patients who developed fever after CAR T infusion and analyzed the association of fever with toxicity (CRS and neurotoxicity) and efficacy (overall response (ORR) and complete response (CR) at day +90 post CAR T infusion). Fever was defined as per Lee criteria (equal to or greater than 38°C). CRS and immune-effector cell associated neurotoxicity syndrome (ICANS) were graded using American Society for Transplantation and Cellular Therapy grading system.ResultsFever occurred in 75% (30/40) of patients. Rates of all grade and grade 3+ CRS and ICANS were 75%, 2%, 33% and 10%, respectively. Fever occurred within 24 and 72 hours after CAR T infusion in 40% and 53% of patients, respectively. Fifty percent of patients received tocilizumab (toci) for CRS. After the first dose of toci, fever recurred in 38% of the patients, of which 67% had recurrence within 24 hours. Day +90 CR rates were 43% and 10% in patients with and without fever, respectively (Table 3).ConclusionWhile fever is common after CAR T-cell therapy, early-onset and higher magnitude do not appear to affect safety or efficacy of CAR T. Absence of fever may affect response to CAR T.     

New WHO histologic classification predicts prognosis of thymic epithelial tumors: a clinicopathologic study of 200 thymoma cases from China

BACKGROUND: In 1999, a World Health Organization (WHO) committee published histologic criteria for distinct thymoma entities (labeled as Type A, AB, B1, B2, B3 thymomas) and for the heterogeneous group of thymic carcinomas, collectively called Type C thymomas. Whether WHO-defined histologic thymoma subtypes are of independent prognostic relevance has yet to be proved. METHODS: Two hundred thymomas from the Shanghai Chest Hospital with a mean follow-up time of 15 years (range, 1-246 months) were studied for the relevance of WHO histologic subtype and other factors (stage, therapy, and myasthenia gravis [MG]) for survival. RESULTS: In order of frequency, 68 patients (34.0%) had Type AB, 39 (19.5%) had Type B2, 36 (18.0%) had Type C, 27 (13.5%) had Type B3, 17 (8.5%) had Type B1, and 8 (4.0%) had Type A thymoma. Five cases (2.5%) were rare thymomas not mentioned in the WHO classification. Survival data showed significant differences among the histologic subtypes (log rank test: P < 0.001). Among patients with Type A and AB thymomas, none died of tumor; of the Type B1 thymoma patients, only one (5.9%) died at 22 months. Type B2, B3, and C thymomas had a significantly worse prognosis with 5-year survival rates of 75.0%, 70.0%, and 48.0%, respectively. Ninety-six patients (48.0%) were in Masaoka Stage I, 26 (13.0%) were in Stage II, 65 (32.5%) were in Stage III, and 13 (6.5%) were in Stage IV. Stage was highly significant in predicting survival (log rank, test P < 0.001). The association between histologic subtype and invasive behavior (stage) was statistically significant (P < 0.001). However, histology was an independent predictive factor of survival in Stage I and II thymomas: Type B2, B3, and C thymomas had a worse prognosis than Type A, AB, and B1 thymomas (log rank test: P < 0.003). Thirty patients (15.0%) presented with MG. MG was significantly more frequent in Type B2 and B3 than in Type A, AB, and B1 thymomas (P < 0.01). On multivariate analysis, MG had no adverse effect on survival (P = 0.17). Radiation or chemotherapy improved patients' survival at 5 and 10 years in Type B2, B3, and C thymomas (log rank test: P < 0.003). CONCLUSIONS: Tumor stage is the most important determinant of survival in thymoma patients, but the WHO histologic subtype is an independent prognostic factor in Stage I and II thymomas, among which WHO Type A, AB, and B1 thymomas form a low-risk group. Patients with high-risk thymomas might profit from novel adjuvant radiochemotherapy regimens.     

Lymphocyte predominance Hodgkin's disease. A clinicopathologic reassessment

A clinicopathologic analysis of 35 cases of lymphocyte predominance Hodgkin's disease (LPHD) was performed, and the relationship between various histologic features and stage at presentation was examined. The series comprised 31 male and 4 female patients with a median age of 32 years. Twenty patients had Ann Arbor Stage I disease; 5, Stage II; 8, Stage III; and 2, Stage IV. Eight cases showed a multifocal epithelioid histiocytic reaction; six of these had advanced-stage (III or IV) disease (P = 0.003). Five cases contained relatively frequent atypical mononuclear cells; four of these were Stage III or IV (P = 0.017). A purely diffuse growth pattern was also associated with high stage (P = 0.031). Presence of nodularity correlated with low stage (P = 0.031). During follow-up (median, 4 years; range, 2.5 months-18 years) there was a high incidence of second neoplasms (2 large cell lymphomas, 3 non-hematologic malignancies). LPHD manifests greater diversity of stage at presentation than originally thought. A high content of epithelioid histiocytes, relatively frequent atypical mononuclear cells, and diffuse histology appear to define subsets associated with advanced-stage disease. The correlation of nodular growth pattern with low-stage disease is consistent with the distinctive behavior and derivation of nodular LPHD.     

Benign Fibrous Histiocytoma in Hodgkin's Disease

A case of benign fibrous histiocytoma in a patient with previous Hodgkin's disease is reported. Benign fibrous histiocytoma consists of a proliferation of benign histiocytes in addition to inflammatory cells and occasional Reed-Sternberg-like cells. Hodgkin's disease is considered a malignant disorder of the monocyte-histiocyte cell line but also includes benign inflammatory cells as part of its histological picture. The possibility that these two entities are biologically related is considered. The pathogenic relationship between both entities is discussed in the context of the immune dysregulation associated with Hodgkin's disease.     

Malignant fibrous histiocytoma of the lung.

Two malignant fibrous histiocytomas arising primarily in the lung are described. The first was a large tumor of the right lower lobe in a 53-year-old man. The other tumor was found incidentally on routine roentgenograms in a 25-year-old woman and involved the left main pulmonary artery. The lesions could be resected but both patients developed early cerebral metastases. The neoplasms were predominantly fibroblastic, had a characteristic storiform pattern, and included large histiocytes with bizarre nuclei and a vacuolated cytoplasm. The ultrastructure of the cells in the fibroblastic areas was characterized by irregular nuclei and a cytoplasm with a well-developed endoplasmic reticulum and dilated cisternae. Some cells lacked the prominent endoplasmic reticulum of fibroblasts and others were characteristic histiocytes with numerous cytoplasmic lysosomes. The cases appear to be the first reported primary malignant fibrous histiocytomas of the lung.     

Hormonal effects of Depo-Provera in cervical smears: a comparison with Triphasil and postmenopausal effects

BACKGROUND: Long-acting injectable contraceptive agents may cause changes in cervical smears that could impair the detection of epithelial abnormalities. The objectives of the current study were to 1) compare the hormonal effects of depot-medroxyprogesterone acetate (Depo-Provera) (DP) in cervical smears with those of levonorgestrel and ethinyl estradiol (Triphasil) (TP) and postmenopausal (PM) changes; and 2) determine whether the duration of DP use affects squamous maturation. METHODS: Satisfactory cervical smears from 50 DP users, 55 TP users, and 51 PM patients were evaluated blindly for: 1) squamous cell curling, crowding, cytolysis, and navicular cell formation; 2) pseudoparakeratosis, blue blobs, and histiocytes; 3) endometrial cells and blood; 4) single or enlarged endocervical nuclei and mucin-depleted endocervical cells; 5) lactobacilli and coccobacilli amounts; and 6) squamous maturation (ratio of parabasal:intermediate:superficial cells). RESULTS: No statistically significant differences were observed for blue blobs, histiocytes, blood, endometrial cells, or single or enlarged endocervical nuclei among smears from the three groups. More smears from DP and TP users demonstrated squamous cell curling, crowding, and cytolysis as well as navicular cells and abundant lactobacilli compared with smears from PM patients. There were more PM smears with pseudoparakeratosis and mucin-depleted endocervical cells compared with the other groups. The majority of PM smears (98%) demonstrated predominantly parabasal cells with some intermediate cells. The majority of DP (86%) and TP (93%) smears demonstrated mostly intermediate and some superficial cells, regardless of the duration of DP use. CONCLUSIONS: Certain progestational-dependent effects (i.e., curling, crowding, navicular cells, and abundant lactobacilli) were identified more often in TP users compared with DP users and less often in PM patients. The mostly parabasal pattern observed in smears from PM patients contrasted with the predominantly intermediate pattern found in smears from DP and TP users. The duration of DP use did not appear to have any effect on squamous maturation.     

Granular cell variant of atypical fibroxanthoma

We report a case of atypical fibroxanthoma of the ear in which the dominant part of the tumor has granular cell appearance. Areas identical to conventional atypical fibroxanthoma were present only at the lateral infiltrating borders. Histologically the granular cells resembled those of the classical granular cell tumors but exhibited significant pleomorphism and a high mitotic rate. Immunostains for vimentin, CD68 and NK1/C3 were positive but for S-100, HMB-45, myogenic and epithelial markers were negative. The predominance of the granular cells in an atypical fibroxanthoma supports the concept that a small subset of tumors with granular cell phenotype are of nonneural origin.     

皮肤鳞状细胞癌NF-κB p65表达的临床价值

目的：研究NF-κB p65蛋白在皮肤鳞状细胞癌中表达的临床诊断价值。方法选择30例皮肤鳞状细胞癌患者以及10例健康体检者。比较两组患者的NF-κB p65蛋白阳性表达率,分析NF-κB p65蛋白的表达与皮肤鳞状细胞癌患者的临床病理特征之间的关系。结果皮肤鳞状细胞癌患者体内的NF-κB p65蛋白阳性表达率高于正常组织,差异有统计学意义（P﹤0.05）。皮肤鳞状细胞癌组织中NF-κB p65蛋白阳性表达率与侵袭深度、分化程度、临床分期、淋巴结转移、远端转移相关,差异有统计学意义（（P﹤0.05）;与性别、年龄、肿瘤大小无关,差异无统计学意义（（P﹥0.05）。正常皮肤组织鳞状上皮细胞核基本未见p65表达,胞质p65表达阳性;癌前病变中,病变鳞状上皮细胞细胞核见散在p65弱表达,胞质弱阳性;高度恶性鳞状细胞癌组织病变鳞状上皮细胞细胞核可见较多p65表达,胞质呈弥漫性阳性,血管内皮细胞胞核表达,胞质散在弱阳性。结论 NF-κB p65蛋白参与皮肤鳞状细胞癌的形成和发展,随患者病情的进展,NF-κB p65蛋白的阳性表达率越高。     

BLA.36: a glycoprotein specifically expressed on the surface of Hodgkin's and B cells.

Anti-BLA.36 is an antibody that recognizes a glycoprotein with an apparent molecular weight of 36 kilodaltons, termed B lymphocyte antigen (BLA.36). By using an immunochemical staining technique, BLA.36 was found to be specifically expressed on Hodgkin's and human B cell lines including early B progenitor cells. Other cell lines representing T cell lymphomas, non-B large cell lymphomas, melanomas and carcinomas were consistently negative. BLA.36 is distinct from the previously identified antigens of hematopoietic cell lineage. The specificity of expression of BLA.36 in tissue sections mirrored that of cell lines. In normal tissues, BLA.36 was detectable predominantly on cells in the germinal center and mantle zone of reactive follicles in lymph nodes and spleens. In hematopoietic malignancy, the antigen was expressed on the surface of Reed-Sternberg cells, mononuclear Hodgkin's cells and also on malignant cells of B cell lineage. BLA.36 was also observed on lymphoid cells of 10 to 24 week fetal liver: a double-antibody-staining method revealed that these BLA.36-positive cells also contained immunoglobulin mu heavy chain consistent with identification as early B cells. Under these conditions, T lymphocytes, histiocytes, granulocytes, macrophages, stromal cells in lymphoid tissue, and both normal and neoplastic epithelial cells were consistently negative for the expression of the antigen, with the single exception of a variable proportion of Kupffer cells in normal liver. The antibody has already established its usefulness for the identification of Reed-Sternberg and Hodgkin's cells, and also normal and malignant B lymphocytes in frozen as well as formalin-fixed tissue sections. Furthermore, binding of F(ab)2 fragments of anti-BLA.36 to antigen-positive cell lines specifically inhibited the proliferation of cells. Such an effect was eliminated by the removal of the antibody from the culture-medium, suggesting a possible growth-related function of the antigen in Hodgkin's and B cells.     

Cumulative incidence rates for Hodgkin's disease and other hematologic malignancies, with special reference to age-related carcinogenesis

The cumulative incidence rate throughout the life span was analyzed for 4,865 Hodgkin's disease cases, in comparison with 16,015 malignant lymphomas (ML), 1,694 acute lymphocytic leukemias (ALL), 3,967 acute myeloid leukemias (AML), 2,109 chronic myeloid leukemias (CML), and 4,752 chronic lymphoid leukemias (CLL) in US white reported in the SEER program during 1973-1981. A log-linear increase was observed in ML, AML, CML, and CLL throughout the life-span, but only in childhood in ALL. Hodgkin's disease showed a steep increase until age 20-24, and then the increase became much more gradual. The cumulative incidence rates for males and females were parallel for ML and leukemias, but diverged for Hodgkin's disease (the rate for females had a lower slope than that for males after age 20-24). This difference was mainly caused by a lower frequency in females of mixed cellularity and lymphocyte predominance subtypes. The incidence curve of Hodgkin's disease was consistent with the two-stage model of carcinogenesis; it is likely that the proliferation of progenitor cells peaks at a young age and that the death rate of so-called intermediate cells is a primary influence during the subclinical stage. The cytogenesis of Hodgkin's disease and the histologic variation with special reference to the T-zone histiocytes suggest that a strong host defense mechanism against neoplastic change is involved, rather than different etiologic influences.     

Morphophenotypic characteristics of intralymphatic cancer and stromal cells susceptible to lymphogenic metastasis

The intravessel microenvironment has significant effects on cancer metastasis. The aim of the present study was to determine how the morphologic and immunophenotypic features of cancer cells and infiltrating stromal cells within the permeated lymphatic vessels are associated with lymphogenic metastasis. A total of 137 primary lung adenocarcinoma patients with extratumoral lymphatic permeations were examined. Morphologically, the floating cancer nests within the permeated lymphatic vessels were divided into two types: Type A, consisting of a single large cancer nest; and Type B, consisting of multiple small cancer nests. We compared the clinicopathologic characteristics and the immunophenotypes of the cancer cells and infiltrating stromal cells between the Type A and Type B nests. Eleven of 54 Type A patients (20%) had intrapulmonary metastases, compared with 36 of 83 Type B patients (43%; P = 0.006). Immunohistochemically, Type B cancer cells expressed significantly higher levels of CD44 than Type A cancer cells (mean scoresAUTHOR: Scores ‐ what is this score? Is it the number of cells expressing CD44 or the concentration of CD44 or some other type of scoring system? 43.0 vs 20.5, respectively) and E‐cadherin (60.5 vs 31.5, respectively), but lower levels of Geminin (11.9% vs 20.3%, respectively) and cleaved caspase 3 (2.4% vs 7.8%AUTHOR: 11.9% vs 20.3%, respectively) and cleaved caspase 3 (2.4% vs 7.8%, – what do the percentages here refer to? The number of cells expressing geminin and caspase 3? The levels of these factors? Please clarify., respectively). Moreover, a significantly larger number of CD204‐positive macrophages were present within the cancer‐permeated lymphatic vessels in Type B patients than in Type A patients (mean number 9.5 vs 4.6, respectively). The present study reveals that intralymphatic cancer cell and stromal cell phenotypes are susceptible to lymphogenic metastasis, suggesting that lymphogenic metastasis may be affected by the intralymphatic microenvironment they create. (Cancer Sci 2012; 103: 1342–1347)     

Human immunodeficiency virus-associated Hodgkin's disease. Clinicopathologic studies of 24 cases and preponderance of mixed cellularity type characterized by the occurrence of fibrohistiocytoid stromal cells

Hodgkin's disease (HD) was diagnosed in 24 patients who were either seropositive for human immunodeficiency virus (HIV) (21) or members of a high-risk group (three), but had not developed acquired immune deficiency syndrome (AIDS). Clinical presentation of the disease was characterized by constitutional symptoms in all, especially fever (23/24) and disseminated disease (22/24) at diagnosis. Mediastinal adenopathy was rare. Bone marrow involvement was particularly frequent (12/24), and a positive bone marrow biopsy preceded lymph node biopsy in 5 of the 12. Histopathologic features of these tumors included an increased number of nonlymphoid stromal cells, i.e., histiocytic and/or fibroblastoid. In some tumors these fibrohistiocytoid stromal cells were arranged in bundles, but distinct nodule with birefringent collagen band formation was not observed. Twenty-two patients were treated, most with combination chemotherapy; one was untreated; one, unknown. Sixteen, including the one untreated, died with disease at 3 to 25 months; one died of an unrelated cause; four were alive at 3 to 24 months; three were lost to follow-up. Frequent bone marrow involvement at presentation suggests the usefulness of the bone marrow biopsy for diagnosis in subjects at risk, especially when they present with spiking fever of unknown origin. Contrary to most previous series, virtually all of our cases were of mixed cellularity type, characterized by increased fibrohistiocytoid stromal cells in place of depleting lymphocytes. The classic nodular sclerosing feature with birefringent collagen band formation was not observed. In conclusion, HIV-associated HD was characterized by advanced stage with fever at presentation, preponderance of mixed cellularity histologic type with increased fibrohistiocytoid stromal cells, and poor outcome. Hodgkin's disease in AIDS patients presents an intriguing biological model to study the role of stromal histiocytes in immunodeficient patients.     

Histopathologic features of composite ganglioneuroblastoma. Immunohistochemical distinction of the stromal component is related to prognosis

Histopathologic features of 18 cases of composite ganglioneuroblastoma (CGNB) were studied with immunohistochemical staining techniques using antibodies against S-100 protein (S-100), ferritin (FER), and leukocytic common antigen (LCA). Cases of CGNB were divided on the basis of the morphologic features of neuroblastic elements into three prognostic subgroups: "Type A Intermixed," having individual microscopic nests of neuroblasts (N = 4, 100% survival); "Type B Intermixed," having microscopic aggregates of multiple neuroblastic nests (N = 6, 67% survival); and "Nodular," having grossly visible nodule(s) of neuroblastic proliferation (N = 8, 0% survival). Survival rates are significantly different for the prognostic subgroups (P less than 0.025). Each prognostic subgroup demonstrated an immunohistochemically distinct pattern of stromal cell composition in the neuroblastic elements: Type A Intermixed had numerous S-100 cells and no FER cells, Type B Intermixed contained many S-100 cells and a moderate number of FER cells, and Nodular had few S-100 cells with many FER cells. The S-100 and FER scores, determined by counting the positive cells through a line sampling method, differed significantly between these prognostic subgroups. Lymphocytic aggregations in tumor tissue evaluated by volumetric assessment with LCA staining, on the other hand, showed no contribution in predicting the outcome of the patients. There was also an inverse relationship between S-100 and FER score, suggesting a relationship between the relative predominance of these stromal cell types, tumor histopathologic features, and the biologic behavior of CGNB.