Thymic carcinoma: a clinicopathological and immunohistological study of 19 cases

Aims:  To study 19 cases of primary thymic carcinoma in order to define the clinicopathological features and the precise histochemical profile of this rare and heterogeneous group of tumours of the anterior mediastinum.
Methods and results:  The study group consisted of 13 males and six females, with a mean age of 58.5 years (range 29–75 years). Superior vena cava syndrome and chest pain were the main presenting symptoms. Three patients were asymptomatic. No patient had myasthenia gravis. Six different histological types were identified: neuroendocrine tumours (six patients), epidermoid carcinoma (five patients), sarcomatoid carcinoma (three patients), lymphoepithelioma-like carcinoma (two patients), mucoepidermoid carcinoma, clear cell carcinoma, and undifferentiated carcinoma (one patient each). The clear cell carcinoma was associated with a thymic cyst. No association with thymoma was observed. Surgical resection, performed in 10 cases, was complete in two. Sixteen patients received thoracic radiation, and 11 received systemic chemotherapy. Follow-up information was available in 16 cases; 12 patients presented with local or metastatic relapse, and 10 patients died of their tumour. The overall 5-year survival was 14.5%.
Conclusion:  Primary thymic carcinoma is a very heterogeneous group of tumours of the anterior mediastinum with an aggressive clinical behaviour, and a poor overall prognosis.     

Peripheral T-cell lymphoma in childhood. A clinicopathological study of six cases

A review of the pathological material from 42 children with non-Hodgkin's lymphoma seen over a 44 month period revealed 10 large cell tumours. Of these, six were classified as peripheral T-cell lymphoma, an entity rarely reported in childhood. Three patients were boys and three girls (median age 9.5 years), and extranodal presentation was a feature of two patients. Five had high-grade tumours; of these, three were classified as large cell anaplastic, Ki-1 positive and two as pleomorphic large cell. The remaining patient had a low-grade tumour of angioimmunoblastic type. T-cell subsets were examined in three cases and showed the following phenotypes: CD4-, CD8-; CD4+, CD8-; CD4-, CD8+. Three of the patients with high-grade tumours died, with a mean survival of 22 weeks. The remaining patients are alive and clinically disease-free for between 10 and 24 months after treatment.     

An immunohistological study of human lymphoma.

In this study the problems encountered in staining immunoglobulin (Ig) in sections of paraffin-embedded human lymphoma samples have been investigated. It was found that the "masking' of cytoplasmic Ig, which occurs when tissues are fixed in formol saline (the fixative employed in most previous studies), can be avoided by the use of mercury-based fixatives. When non-Hodgkin's lymphoma samples fixed in this way were studied it was found that cytoplasmic Ig labelling of both lymphoid and histiocytic cells is often attributable to non-specific uptake of serum proteins. This phenomenon probably accounts for a number of published anomalous immunoperoxidase staining results in human lymphoma (e.g. the presence of both kappa and lambda chains in the same neoplastic cell). Double immunoenzymatic labelling (using alkaline phosphatase and peroxidase) proved valuable in the elucidation of this phenomenon. When staining due to absorbed Ig was discounted it was possible to demonstrate monoclonal Ig labelling in seven out of sixteen cases of non-Hodgkin's lymphoma. In each case IgM was found in association with a single light chain type and these results were in agreement with those obtained by direct immunofluorescent labelling of cryostat sections. In a further case u chains without associated light chains were demonstrated by immunoperoxidase staining. Seven cases of Hodgkin's disease were studied by immunoenzymatic techniques. Although IgG was frequently found in Reed-Sternberg and Hodgkin's cells its presence was not attributable to non-specific uptake of serum protein since albumin was absent or only present in small amounts. These findings are in support of the macrophage origin of these cells.     

Tumours in Iceland. 15. Ependymoma. A clinicopathological and immunohistological study.

Thirteen ependymomas reported to the Icelandic Cancer Registry during a 32-year period (1955-1986) were histologically reviewed and reclassified according to the WHO Histological Typing of Tumours of the Central Nervous System. The annual incidence rate of ependymoma was 0.20/100.000. Clinical observations and data on biological behaviour and immunohistochemistry are presented. Four tumours were supratentorial, six infratentorial and three intraspinal. There were ten males and three females with a mean age of 32 years (range 2.5-68). The mean postoperative survival of nine surgically treated patients was 35.5 months. Histologically, eight tumours were classical ependymomas, three anaplastic and two myxopapillary. Of 11 tumours stained for GFAP, nine were positive. Nine of 10 tumours tested were positive for vimentin, five for NSE and four for S-100. None of the 10 tumours showed reactivity with AFP, CEA, chromogranin, desmin, factor VIII, keratin or neurofilament.     

A clinicopathological study of nodal marginal zone B-cell lymphoma. A report on 21 cases

AIMS: To report the clinicopathological findings of 21 cases of primary nodal marginal zone B-cell lymphoma (NMZL). NMZL is a recently characterized lymphoma and few series have been published. METHODS AND RESULTS: The clinical data were characteristic of a disseminated disease at presentation: presence of peripheral and abdominal lymph nodes, bone marrow involvement (62%), disease stage III and IV (76%), elevated lactate dehydrogenase (LDH) (48%). Other features included peripheral blood involvement (23%), anaemia (24%), thrombocytopenia (10%) and presence of serum M component (33%), while the previously reported association with hepatitis C virus and cryoglobulinaemia was not found. Relapses were frequent but the majority of patients receiving chemotherapy had a good initial response. Morphological features were heterogeneous and there were some differences compared with other marginal zone B-cell lymphomas (MZL). Pure monocytoid B-cell lymphomas were rare (10%) but a minor component of monocytoid B cell was observed more frequently (23%). Plasmacytoid or plasmacytic differentiation was a very common feature (61%). Large cells and a high mitotic count were also frequent (57%). CONCLUSION: NMZL can be distinguished from splenic MZL and extranodal MZL by its aggressive morphology and disseminated disease at presentation.     

Acute viral lymphadenitis mimicking low-grade peripheral T-cell lymphoma. A clinicopathological study of nine cases

Acute viral lymphadenitis, especially infectious mononucleosis (IM), often shows the presence of Reed-Sternberg-like cells, resulting in confusion with Hodgkin's disease. However, acute viral lymphadenitis requiring differential diagnosis from non-Hodgkin's lymphoma is not widely recognized. We describe the clinicopathological and immunohistochemical features of lymph node lesions from nine such patients which pose serious problems of differential diagnosis from low-grade peripheral T-cell lymphoma. There were three males and six females with ages ranging from 21 to 44 years (median 25 years). All patients had "B" symptoms and multicentric lymphadenopathy. The clinical course was also self-limiting. Each lymph node specimen showed an obvious expansion of an interfollicular area by pleomorphic and polymorphous infiltration with an increased number of arborizing postcapillary venules. The infiltrate was composed of variable numbers of small and medium-sized lymphocytes, immunoblasts, plasma cells in various stage of maturation and occasional granulocytes. The small lymphocytes usually had regular round nuclei, whereas the medium-sized lymphocytes occasionally showed nuclear pleomorphism. Hyperreactivity of B-lymphocytes, including hyperplastic germinal centers and/or foci of monocytoid B-cells, was seen in parts of the lesion. The majority of the interfollicular T-lymphocytes, including T-immunoblasts, expressed CD8 antigen. Various numbers of TIA-1-positive small and medium-sized T-cells were observed in the paracortical area. Despite these findings, the overall histological picture of this series posed serious difficulties when differentially diagnosing this condition from low-grade peripheral T-cell lymphomas such as angioimmunoblastic T-cell (AILD) and T-zone types, indicating that viral lymphadenitis occasionally presents with histological features of AILD and T-zone lymphomas. To avoid overdiagnosis and overtreatment, we emphasize the need to pay careful attention to the clinical and laboratory findings as well as the morphological features.     

Childhood Ki-1 lymphoma. A report of two cases

Two cases of childhood Ki-1 lymphoma occurred with the expression of Ki-1+/HLA-DR+/IL-2R+/EMA+/Leu-M1-/pan-T antigens-/pan-B antigens- in neoplastic cells. Patient 1 with nodular skin lesions expressed Leu-2a+ in the neoplastic cells and died 14 months later. Patient 2 with lymph node swelling and hepatosplenomegaly exhibited Leu-3a+ in the neoplastic cells and remains free of disease. The Leu-2a+ (case 1) or Leu-3a+ (case 2) findings suggest that the neoplastic cells in both cases were derived from T-lymphocyte lineage. However, Southern's blot analysis did not reveal any clonal rearrangements of T-cell receptor genes in the autopsy material from case 1. The Leu-3a+/Mcs-2+ finding in case 2 may indicate that the neoplastic cells were derived from monocyte/macrophage lineage.     

Lymphoplasmacytoid lymphoma: an immunohistological study

Eighteen cases of lymphoplasmacytoid lymphoma (LPL) have been immunophenotypically characterized with a panel of 26 monoclonal antibodies. All cases expressed leucocyte common antigen, class II MHC and stained with B cell markers (CD19, CD20, CD22) although a variable proportion of tumour cells were noticed to have lost some B cell marker expression. There was some phenotypic heterogeneity with variable immunostaining with KB61, CD21, and CD5. A variable proportion of cells in all cases contained cytoplasmic immunoglobulin. Surface immunoglobulin light chain restriction was demonstrated in 11 cases and heavy chain predominance in 16 cases. Few tumour cells were proliferating as indicated by Ki67 immunostaining. A wide variation in number of macrophages and T lymphocytes were present in association with the tumours. A significant association between the expression of CD5 and the presence of peripheral blood lymphocytosis was noticed (p less than 0.003) but there was no association between CD5 and co-expression of IgM and IgD. This data supports an origin from non-germinal centre cells for LPL and suggests that CD5 expression by B cells may be related to lymphocyte migration. LPL shows some immunological heterogeneity and can present diagnostic difficulties, but its poor prognosis makes it an important category of lymphoma to recognise.     

Mantle cell lymphoma: a clinicopathological study of 55 cases

A recently described unifying proposal for mantle cell lymphoma has led to the formulation of strict diagnostic criteria based on morphology, immunology and molecular data to define this specific entity. Previous studies were often based on broader definitions such as centrocytic lymphoma, intermediately differentiated lymphoma or mantle zone lymphoma and, therefore, included a variety of entities with some, but not all, features ascribed to the mantle cell lymphoma. Since the publication of the unifying proposal no comprehensive studies have been published to confirm and support it. We selected 55 cases of mantle cell lymphoma collected in our institution in order to evaluate the validity of the proposal and, by using strict criteria, we analysed the morphological features, their variations and the changes occurring in the course of the disease as well as its clinical behaviour. The analysis of this material demonstrates that mantle cell lymphoma affects predominantly elderly males presenting with an advanced stage of disease. Twenty-four out of 55 patients died with, or of, the disease with a median survival of 32 months, even though most of them received aggressive chemotherapy. In all cases the histological features were strikingly uniform and most cases had a diffuse growth pattern. The neoplastic cells corresponded to small cleaved cells with a minimal variation in shape and size from one case to the other. The phenotype of the neoplastic cells was remarkably constant with expression of several pan-B cell markers, IgM, IgD and CD5, and lack of CD10 and CD23. Sixteen cases, which were followed by consecutive biopsies, showed only slight morphological changes during the course of the disease and only four cases showed histological progression. Forty cases were documented by cytogenetics, of which 15 showed t(11; 14)(q13;q32). We examined 28 cases for DNA rearrangement of the BCL-1 locus; it was detected in 50% of the cases, with most breakpoints occurring at the major translocation cluster. This study demonstrates that when selection criteria are strictly applied, mantle cell lymphoma represents a disease entity with a uniform presentation, distinctive morphology, immunophenotype and a strong association with t(11;14)(q13;q32).     

Clear cell lymphoma: a clinicopathological study of four cases

Four cases of clear cell lymphoma were studied by means of light and electron microscopy, enzyme-histochemistry, and E- and EAC-rosette formation. On light microscopic examination the tumors were seen to be composed mainly of round, oval, or slight irregular cells with water-clear, abundant cytoplasm. The neoplastic cells has round, oval, or convoluted nuclei with fine, evenly dispersed chromatin and one or more small but distinct nucleoli. On electron microscopic examination the clear cell lymphoma were characterized by lymphoid cells with striking electron lucent cytoplasm with few organelles. According to E-rosette test and enzyme-histochemical findings, the investigators proposed that the clear cell lymphoma may be derived from T-cell lineages. Differentiated diagnoses of clear cell lymphoma from B-immunoblastic sarcoma, pleomorphic cell lymphoma, clear cell sarcoma, and clear carcinomas derived from lung, ovary, or kidney were discussed.     

Reactive proliferative lesions in lymph nodes from rheumatoid arthritis patients. A clinicopathological and immunohistological study.

In 22 cases of rheumatoid arthritis (RA), including 4 cases of malignant RA (MRA), reactive proliferative lymph node lesions were studied clinicopathologically and immunohistochemically. This series included 5 males and 17 females. The period between disease onset and lymph node biopsy ranged from 3 months to 41 years. Generalized lymphadenopathy was noted in 13 cases and constitutional symptoms in 8. The histological findings characteristic of RA were 1) follicular hyperplasia with active germinal centers and 2) polyclonal plasma cell infiltration in the interfollicular area. Studies of intracytoplasmic immunoglobulin showed that gamma-heavy chain-expressing plasma cells were a major component in the interfollicular area in 17 RA cases. However, in 4 MRA cases, a prominent increase of mu chain-expressing plasma cells was recognized in the same area. In the 3 cases for which fresh tissue sections were stained with monoclonal antibodies against lymphocytes, we found that the majority of T cells in the interfollicular area had helper/inducer markers. The identical locations of the T cell population and plasma cells indicated that both played a role in the proliferation and/or differentiation of B cells in lymph nodes in RA.     

皮下脂膜炎性T细胞淋巴瘤临床病理分析

目的分析皮下脂膜炎性Ｔ细胞淋巴瘤的病理形态和生物学行为特点,并对其分类命名作一探讨。方法用ＨＥ和免疫组化ＡＢＣ方法对４例原发并定位于皮下脂肪组织中的Ｔ细胞淋巴瘤进行临床病理学和免疫组织化学观察。结果４例病人均表现１～３ｃｍ的皮下结节,伴高热,临床经过凶猛,短期死亡。组织学上以肿瘤细胞（ＣＤ４５ＲＯ阳性）浸润脂肪小叶之间及大量豆袋细胞（ｂｅａｎｂａｇｃｅｌ,ＣＤ６８阳性）为特征。结论皮下脂膜炎性Ｔ细胞淋巴瘤是一种恶性度很高的外周Ｔ细胞淋巴瘤。     

脾脏非霍奇金淋巴瘤临床病理学研究

目的 探讨脾脏非霍奇金淋巴瘤(SNHL)的形态学特点、免疫表型及鉴别诊断。方法 对39例SNHL进行形态学观察及免疫组化ABC法分析，使用抗体包括CD3、CD45RO、CD56、CD79α、CD20、CD68、Mac387、CD5、CD10、bcl—2、CD23、CD43、cyclinD1、IgM、IgD等。结果 39例SNHL中有B细胞淋巴瘤(BCL)24例，包括小淋巴细胞性淋巴瘤(SLL)4例，套细胞淋巴瘤(MCL)4例，滤泡性淋巴瘤(FL)5例，边缘区淋巴瘤(MZL)6例，弥漫大B细胞性淋巴瘤(DLBCL)5例，其中2例为大多叶核细胞淋巴瘤。T细胞淋巴瘤(TCL)11例，其中肝脾T细胞淋巴瘤2例，非特异性TCL9例。组织细胞性淋巴瘤4例。结论 脾脏淋巴瘤病理类型多样，掌握其形态学特征，熟悉各类型的免疫表型的异同点对诊断与鉴别诊断有重要意义。     

Nasopharyngeal and nasal malignant lymphoma: a clinicopathological study of 54 cases

Forty-one cases of nasopharyngeal and 13 cases of nasal malignant lymphoma have been examined histologically and immunohistochemically. All of the cases were non-Hodgkin's lymphoma; one case was of follicular type and the remaining 53 were of diffuse type. Large cell lymphoma comprised 48% of cases and most of the immunoblastic lymphomas showing pleomorphism occurred in the nose. Twenty-seven cases were of T-cell and 21 of B-cell phenotype. The predominance of T-cell lymphoma was due to an increased incidence of these in the nose, the T:B ratio of 3.33:1 contrasting with a 1:1.05 ratio in the nasopharynx. Nasopharyngeal lymphomas seem to show an intermediate incidence between the T-cell predominance in the nose and a B-cell predominance in the oropharynx. Since the large cell type of lymphoma was predominant, the differential diagnosis from undifferentiated carcinoma is important and is facilitated by the use of immunostaining methods.     

B cell lymphoma with IRF4 rearrangement: A clinicopathological study of 13 cases

Interferon regulatory factor 4 (IRF4) rearrangement is commonly detected in patients with a range of lymphoproliferative malignancies, including myelomas, large B cell lymphomas and low-grade B cell neoplasms. However, IRF4 rearrangement is generally a relatively rare finding in these latter two cancer types. In the present article, we describe and summarize the clinicopathological and genetic features of 13 cases of B cell lymphoma with IRF4 rearrangement, including 12 cases of large B cell lymphoma and one case of low-grade lymphoma exhibiting such rearrangement. These cases were detected in six females and seven males between 14 and 71 years of age. From a morphological perspective, large B cell lymphoma tumors included in this analysis exhibited large neoplastic cells in diffuse or follicular patterns, while the case of low-grade lymphoma mainly composed of small lymphocytes. All analyzed cases exhibited a split in the IRF4 gene consistent with IRF4 translocation. Three of six analyzed large B cell lymphoma cases harbored IGLL5 mutations. Mutations in SAMHD1 were detected in the low-grade lymphoma with IRF4 rearrangement case. In summary, our results offer further insight into the morphological and molecular heterogeneity of cases of B cell lymphoma exhibiting IRF4 rearrangements.     

Multicolor karyotyping and clinicopathological analysis of three intravascular lymphoma cases.

Intravascular lymphoma (IVL) is a rare neoplastic disease characterized by the presence of large malignant lymphoid cells in small vessels. It is often diagnosed at autopsy. Clinical manifestations are typically neurologic and dermatologic. Karyotypic abnormalities have been described in a small number of cases and have revealed complex alterations in the majority of cases. We have identified three cases of IVL with varied clinicopathological findings. Karyotypic analysis was undertaken by standard G-banding and supplemented by multi-colored karyotyping (M-FISH) to decipher the chromosomal content of marker chromosomes and undefined additions. M-FISH clarified the chromosomal abnormalities in two cases and unveiled cryptic translocations der(10)t(10;22), der(17)t(17;22), and balanced t(11;14). Comparison with previously published karyotypes revealed prominent involvement of chromosomes 1, 3, 6, 11, 14, and 18, similar to the pattern of clonal evolution in other B-cell lymphomas. The most frequent alterations seen were -6 or 6q- and +18 or dup(18q), with a minimally deleted region located at 6q21-q23 and a commonly amplified region located at 18q13-q23, respectively. Few differences between the classical and Asian variant of this disease were apparent at the karyotypic level. Cytogenetic analysis of additional cases supplemented by multicolor karyotyping may help identify the full spectrum of genetic alterations associated with IVL and assist in the delineation of the critical mutations associated with initiation and progression of this disease.     

Composite marginal zone B-cell lymphoma and classical Hodgkin's lymphoma: a clinicopathological study of 12 cases

AIMS: Classical Hodgkin's lymphoma (cHL) rarely coexists as composite lymphoma with B-cell non-Hodgkin's lymphoma (B-NHL). We characterized 12 cases of composite marginal zone B-cell lymphoma (MZBL) and cHL by immunohistochemistry and molecular biology. METHODS AND RESULTS: Eight patients had gastric MZBL of mucosa-associated lymphoid tissue (MALT)-type, in five cases with a diffuse large B-cell lymphoma component. Concurrent cHL was observed either in the stomach wall, regional, or distant lymph nodes. One patient each had composite pulmonary/thyroid MZBL of MALT-type and cHL. In two cases, nodal composite MZBL and cHL was observed. cHL displayed features of mixed cellularity type in 10 cases, while in two cases only scattered Hodgkin- and Reed-Sternberg (H/RS) cells were noted. H/RS cells expressed CD30, multiple myeloma oncogene 1 protein (MUM1P), p53 (100%), CD15 (58%), CD20 (58%) and Epstein-Barr virus-associated LMP1 (50%). No t(11;18)(q21;q21) was detected in composite MZBL of MALT-type and cHL. CONCLUSIONS: MZBL and cHL may occur as composite lymphoma, possibly reflecting clonal lymphoma progression. Derivation from extranodal MZBL of MALT-type should be excluded in cases in which a diagnosis of primary extranodal cHL is considered.     

Spermatocytic seminoma. A clinicopathological and immunohistochemical study of 7 cases

Spermatocytic seminoma is an uncommon tumor, representing less than 1% of the testicular tumors, occurring most often in old patients. We report 7 cases of this entity. The average age at presentation was 66 years. Tumors had a polymorphic appearance with small, intermediate and large cells, and "spireme" figures. They were pure, with no sarcomatous component. In all cases, the tumor was limited to the testis. In the peritumoral tissue, there was no intratubular germ cell proliferation, and no atrophic testis. Immunostaining was negative for all the classical antibodies tested (cytokeratins, PLAP, lymphoid markers), but all the cases expressed c-kit (100%). This membranous positivity was focal in 4 cases, very strong, and diffuse in the 3 others. Spermatocytic seminoma must be recognized, because its favorable evolution in absence of a sarcomatous component. Adequate treatment consists of orchidectomy alone. Positive staining for c-kit may be helpful for the diagnosis of spermatocytic seminoma.