Mucosa-associated lymphoid tissue-type lymphomas occurring in post-transplantation patients.

Post-transplantation lymphoproliferative disorders (PTLDs) are usually Epstein-Barr virus (EBV)-associated B-cell lymphoproliferative disorders that vary in their morphologic spectrum. Extranodal marginal zone lymphomas of the mucosa-associated lymphoid tissue-type (MALT-type) have not been considered to be part of this spectrum. The authors encountered five such cases recently. The clinical, histopathologic, and immunophenotypic features are reported. There were three men and two women with a mean age of 51.2 years (range, 48-63 years). Two patients were cardiac transplant recipients, two patients were liver transplant recipients, and the remaining patient was a renal transplant patient. Sites of lymphoma were the stomach in three patients and the parotid gland in two patients. Mean time to the lymphoma was 84 months after transplantation. All patients had morphologic features of low-grade extranodal marginal zone lymphomas of the MALT-type, and Helicobacter pylori was present in all three gastric cases. All patients exhibited the B-cell immunophenotype and were negative for EBV by in situ hybridization. These lymphomas were treated with a variety of modalities, including reduction of immunosuppression, antibiotics, surgical resection, radiation therapy, and chemotherapy. At last follow-up, one patient had developed signet ring adenocarcinoma at 27 months but had no evidence of PTLD, one patient relapsed at 17 months but is alive with stable disease at 24 months, and the remaining patients were alive without disease at 11, 12, and 14 months. Extranodal low-grade MALT-type lymphomas can occur in the post-transplantation setting and generally develop years after transplant. As seen in immunocompetent patients, EBV appears to play no role in the pathogenesis of these lymphomas. These lymphomas appear to have more in common with MALT-type lymphomas in nonimmunocompromised patients than conventional PTLDs, although they occur in "at-risk" patients due to their immunosuppressive therapy. These lymphomas do not appear to be clinically aggressive. Recognition of MALT-type lymphomas in the post-transplantation setting as an indolent disease avoids unnecessary treatment.

Auer rod-like inclusions in adult common acute lymphoblastic leukemia.

We report a case of adult common acute lymphoblastic leukemia, defined by enzyme histochemistry and immunophenotypic analysis, which had rod-shaped cytoplasmic inclusions that on Wright's-stained peripheral blood smear resembled Auer rods. Electron microscopic analysis of a buffy coat preparation revealed that the inclusions were not characteristic of Auer rods, but rather that they were composed of concentric lamellar structures with no limiting membrane and were closely associated with the nuclear membrane. Therefore, the presence of Auer rod-like inclusions in blasts on a Wright's-stained peripheral blood smear does not preclude a diagnosis of acute lymphoblastic leukemia.

Combining morphology and flow cytometric immunophenotyping to evaluate bone marrow specimens for B-cell malignant neoplasms.

For this study, 188 bone marrow core biopsy specimens and aspirates analyzed morphologically and by flow cytometric immunophenotyping (FCI) in patients with a previous or new diagnosis of B-cell non-Hodgkin's lymphoma or mature B-cell leukemia were retrospectively reviewed to evaluate patterns of involvement and the usefulness of FCI. The morphologic and FCI results were categorized as follows: positive by morphologic examination and by FCI (39.9%); negative by morphologic examination and by FCI (41.5%); positive by morphologic examination and negative by FCI (11.7%); negative by morphologic examination and positive by FCI (2.6%); suggestive of malignant neoplasm by morphologic examination and positive by FCI (2.1%); and suggestive of malignant neoplasm by morphologic examination and negative by FCI (2.1%). Thus, in 81.4% of cases the morphologic and FCI findings were completely concordant. In 11.7% of cases, the morphologic examination alone detected involvement, and in 4.7% of cases, the FCI data detected involvement in a morphologically negative or "suggestive" bone marrow core. Combining these modalities is essential to evaluate bone marrow specimens for involvement by B-cell non-Hodgkin's lymphoma or B-cell leukemia.

Natural killer cell acute leukemia with myeloid antigen expression. A previously undescribed form of acute leukemia.

An acute leukemia of natural killer cell origin with myeloid antigen expression has not previously been described in the literature. Although lymphoproliferative disorders of large granular lymphocytes may be of natural killer cell origin and may have an aggressive clinical course, the morphology in the blood and bone marrow is that of large granular lymphocytes. An acute leukemia with blastic morphology is described, which was of natural killer cell origin by flow cytometric immunophenotyping (CD45+, CD2+, CD3, CD7+, CD5+, CD4, CD8, CD56+, CD57, CD16, CD13+, CD33+, CD34+, C-Kit+, HLA-DR, TdT) and histochemical staining. This was supported by the lack of T-cell gene rearrangement. The patient had an aggressive clinical course despite therapy for acute lymphoblastic leukemia. The authors recommend routine flow cytometric immunophenotyping of acute leukemia to identify other similar cases to better clinically define this entity.

Identification of CD56 and CD57 by flow cytometry in Ewing's sarcoma or primitive neuroectodermal tumor.

CD56 and CD57 are commonly considered as natural killer and neuroectodermal markers, but their expression has been identified in a wide spectrum of neoplasms including some cases of Ewing's sarcoma (ES) and primitive neuroectodermal tumor (PNET). We report two cases of small, round blue cell tumor (SRBCT), in which flow cytometry immunophenotyping (FCI) detected strong expression of CD56 and CD57 (one case). Immunohistochemical staining with Leu-19 and Leu-7 confirmed the FI results. Although CD56 and CD57 expression is consistent with ES/PNET, it can be potentially misleading if results of FCI are interpreted in the absence of other findings. These cases suggest the utility of FCI in undifferentiated SRBCT. The literature on CD56 and CD57 expression in ES/PNET is reviewed and discussed.

A clinically aggressive, polymorphic, polyclonal posttransplantation lymphoproliferative disorder.

Posttransplantation lymphoproliferative disorders (PTLD) have been divided, based on morphology, into polymorphic and monomorphic types, since findings in the literature reveal that polymorphic PTLD more likely responds to reduced immunosuppression. We report a clinically aggressive, polymorphic (and polyclonal) PTLD despite reduced immunosuppression and discuss possible therapeutic options. In addition, our case suggests that cytogenetic studies may be useful in determining prognosis when DNA molecular techniques do not detect monoclonality.

Biphenotypic hematological malignancy with T-lymphoid and myeloid differentiation: association with t(3;12)(p25;q24.3). Case report and review of the literature.

Biphenotypic hematological malignancies of T-lymphoid and myeloid differentiation are relatively rare and have most commonly been associated with t(8;13). However, this entity is invariably associated with eosinophilia and generally progresses to acute leukemia within a year of diagnosis. We describe a case of a biphenotypic hematological malignancy with T-lymphoid and myeloid differentiation without associated eosinophilia; however, there was an association with t(3;12)(p25;q24.3) as a sole abnormality and progression to acute leukemia within 10 months of presentation. This association with such a malignancy has not previously been described. Additional cases need to be accrued to determine the prognostic significance and clinical implications of such an association.

Is t(6;14) a non-random translocation in childhood acute mixed lineage leukemia?

We report a case of childhood acute mixed lineage leukemia (AMLL) with a translocation t(6;14)(q25;q32) as the main clonal abnormality. A comparison of this case with another one with similar cytogenetics and clinical findings may suggest that t(6;14)(q25;q32) is a non-random occurrence in childhood AMLL.

Jumping translocations of 3q in acute promyelocytic leukemia.

Jumping translocation is a rare phenomenon, seldom reported to occur in cancer. A complex four-way translocation involving chromosomes 3, 9, 15, and 17 was identified in the chromosome study on a patient with a history of an acute promyelocytic leukemia (APL). In the follow-up studies, the same complex rearrangement exhibited a jumping translocation between chromosomes 3 and 9 in one clone and 3 and 6 in another clone. This is the first reported case of jumping translocation in APL.

Simultaneous presence of t(2;8)(p12;q24) and t(14;18)(q32;q21) in a B-cell lymphoproliferative disorder with features suggestive of an aggressive variant of splenic marginal-zone lymphoma.

We report a case of an aggressive variant of splenic marginal-zone lymphona (SMZL) with circulating villous lymphocytes. The karyotype of all examined cells had multiple structural and numerical abnormalities, including two lymphoma characteristic translocations, t(2;8)(p12;q24) and t(14;18)(q32;q21). Based on a literature review of cytogenetic aberrations of splenic lymphoma with villous lymphocytes (SLVL) and SMZL, this is apparently the first documentation of these two translocations in a case of SMZL, and could reflect the heterogeneity of the disorder.

Identifying patients with low-risk clinical stage I nonseminomatous testicular tumors who should be treated by surveillance.

We examined the records of 82 patients with clinical Stage I nonseminomatous germ cell tumors of the testis who, after radical orchiectomy, were treated by surveillance at M.D. Anderson Cancer Center between October, 1981, and March, 1987. Our purpose was to determine whether or not patients with a low risk of relapse can be identified at the time of the initial staging evaluation. In 30 of 82 patients (Group 1), embryonal carcinoma constituted less than 80 percent of the tumor, no vessel invasion was present, and the preorchiectomy serum AFP level was less than 80 ng/dL. No relapses occurred in this group. Fifty-two patients (Group 2) had more than 80 percent embryonal carcinoma or vessel invasion or a serum AFP level higher than 80 ng/dL. Relapse occurred in 24 (46%) of these patients. The difference in the rate of relapse between patients in Group 1 and Group 2 was statistically significant (P less than 0.00001). A separate analysis of teratoma as a predictor of nonrelapse showed that the orchiectomy specimens of 30 of the 82 patients contained more than 50 percent teratoma. Only 1 relapse occurred among 25 patients with more than 50 percent teratoma and no vessel invasion. Our data show that there is a subgroup of patients with clinical Stage I nonseminomatous germ cell tumor who have a very low rate of relapse. We believe these patients can be effectively treated by surveillance and should be spared the morbidity of an unnecessary retroperitoneal lymph node dissection.

Mantle cell leukemia, prolymphocytoid type: a rarely described form.

Leukemic manifestations of mantle cell lymphoma are seen in a minority of cases, usually associated with extensive tumor. Usually the neoplastic cells in the peripheral blood resemble mantle cells with a mature chromatin pattern and irregular nuclear contours, or less frequently with a more "blastic" chromatin pattern. A prolymphocytic leukemia with t(11;14)(q13;q32) has previously been reported; however, a complete flow cytometric immunophenotypic profile was lacking. Mantle cell leukemia, prolymphocytoid type with complete flow cytometric data has not previously been described and is the purpose of this report. We report such a case in a 90 year-old female who presented with an elevated white blood cell count. The diagnosis was based on flow cytometric immunophenotyping and the cytomorphology of the peripheral blood combined with cyclin D1 immunohistochemical staining of the bone marrow. We describe our findings and her clinical course in order to heighten awareness of this previously rarely described entity.

CD5+ true SLL/CLL with plasmacytic differentiation and an unusual 1p36 translocation: case report and review of the literature.

Lymphoplasmacytic lymphoma (LPL) and small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL)are distinct clinicopathologic entities. Although some cases of SLL/CLL may show plasmacytic differentiation and be associated with monoclonal immunoglobulin in serum, such cases appear to be very rare, and if plasma cell differentiation were marked, differentiation of SLL/CLL from LPL could be difficult. We report a rare case of true CD5-positive small lymphocytic lymphoma/chronic lymphocytic leukemia with unequivocal plasmacytic differentiation. This case also showed an abnormality of chromosome 1p36 not previously described in small lymphocytic lymphoma/chronic lymphocytic leukemia.

Composite lymphoma of Hodgkin lymphoma and mycosis fungoides: previously undescribed in the same extracutaneous site.

Mycosis fungoides (MF), diagnosed and limited to the skin, has been associated with the subsequent development of Hodgkin lymphoma (HL), most commonly of the nodular sclerosing (NS) subtype. In the previously described cases, there are none in which the extracutaneous tissue was simultaneously involved by HL and residual/relapsing MF. Here we report a case of HL, mixed cellularity (MC) subtype, arising in an inguinal lymph node in a patient with a previous diagnosis of MF. We describe the immunophenotypic, histologic and immunohistochemical findings of a composite lymphoma containing the HL, MC subtype and MT. The importance of detecting MF in addition to the HL in the extracutaneous site with available diagnostic modalities is highlighted.

Acute promyelocytic leukemia, hypogranular variant, with uncharacteristic staining with chloroacetate esterase.

A diagnosis of the hypogranular variant of acute promyelocytic leukemia (APLv) may be difficult to establish based on cytomorphology alone. However, the great majority of cases have a classical immunophenotype by flow cytometric immunophenotyping (FCI) (CD13+, CD33+, dim CD64+, HLA-DR-, and CD34-) and a classical enzyme cytochemical (EC) staining pattern. [intensely staining with myeloperoxidase, Sudan Black B, and chloroacetate esterase (CAE) and negative with alpha'-naphthyl acetate and butyrate esterases]. Although the immunophenotype of APLv by FCI has varied in the literature (HLA-DR +/- and CD34 +/-), the EC staining pattern has remained constant. We report a case of APLv with characteristic cytomorphology, compatible FCI data (CD13+, CD33+, dim CD64+, HLA-DR +/-, and CD34-), chromosomal detection of t(15; 17), and molecular detection of the PML/RAR alpha fusion gene; however, staining of the leukemic cells with CAE was quite uncharacteristic. We describe our findings.

Paraffin immunoreactivity of CD10, CDw75, and Bcl-6 in follicle center cell lymphoma.

Follicle center cell lymphoma(FCCL) has the following immunophenotype(IP): sIg+, Pan B+, CD10+/-, CD5-, CD23-/+, CD43-, CD11c-, CD25-. In addition, reactivities of a malignant lymphoma with CDw75(LN-1) and bcl-6 are considered indicators of FCCL. Bcl-6 expression is common in Grade 1 FCCL (100%) and rare in other indolent B-cell lymphomas(BCL). In contrast, bcl-2 expression is common in FCCL (80%) and in other BCL subtypes. Since no previous study has correlated paraffin immunoreactivity(PIR) of CD10, CDw75, and bcl-6 in FCCL (Grades 1-3), this is this study's purpose. Twenty-nine FCCL's were identified and reviewed (6, Grade 1; 10, Grade 2; 13, Grade 3) from the Division of Hematopathology, St. Louis University. The diagnoses were based on morphology and immunohistochemistry(IH)(21 cases) +/- the flow cytometric IP(14 cases). The paraffin blocks were stained for CD10 (Novacastra, Vector Laboratories, Burlingame, CA), CDw75 and bcl-6 (DAKO Corporation, Carpinteria, CA). Results showed that, CD10 by paraffin IH(PIH) was positive in 23 [18(strong); 3(moderate); 2(weak)] and negative in 6(3, Grade 2; 3, Grade 3). All CD10-cases were CDw75+; 4, bcl-6+. The two CD10-, bcl-6-cases were Grade 2. CDw75 was positive in 28 cases [16(strong); 11(moderate); 1(weak)] and negative in 1 (Grade 3; CD10+, bcl-2+, bcl-6+). Bcl-6 was positive in 26 [16(strong); 6(moderate); 4(weak)] and negative in 3(Grade 2's). Thus, the sensitivity of CD10, CDw75, and bcl-6 by PIH for FCCL was 79%, 97%, and 90%, respectively. Of the three stains evaluated by PIH in FCCL, CDw75 was the most sensitive, closely followed by bcl-6. CD10 was least sensitive-79%. By combining these 3 stains, the sensitivity was 100%; thus, a combined approach is recommended.

CD7 and CD56-positive primary effusion lymphoma in a human immunodeficiency virus-negative host.

Primary effusion lymphoma is an entity with distinctive features. The majority of cases are diagnosed in patients infected with human immunodeficiency virus. We report a case of pleural-based primary effusion lymphoma in an elderly patient negative for human immunodeficiency virus. By flow cytometry, lymphoma cells expressed CD7, CD38, CD45, CD56, HLA-DR, and kappa surface light chains. A monoclonal rearrangement of the immunoglobulin heavy chain and the presence of human herpesvirus 8 genome were detected. Our case lacked CD30 or CD138 with expression of surface light chains. There was strong expression of CD7 and CD56. These findings are unusual or unique in primary effusion lymphoma. Our report suggests that aberrant expression of T cell and natural killer cell markers can be seen in primary effusion lymphoma.

Expression of p53 protein in advanced head and neck squamous cell carcinoma before and after chemotherapy.

BACKGROUND: The expression of p53 protein has been reported to be in the range of 35% to 67% in head and neck squamous cell carcinoma (HNSCC). Mutations of the gene for p53 protein have been associated with rapidly proliferating tumors, and p53 protein expression has been shown to be a significant predictor of worse survival in surgically resected HNSCC. To determine whether p53 protein expression in advanced (stages III and IV) HNSCC has any impact on tumor response to 2 to 3 courses of paclitaxel (Taxol) and carboplatin, we prospectively studied prechemotherapy specimens from patients with previously untreated, advanced-stage HNSCC. We also attempted to study residual tumors after chemotherapy to determine if the p53 status of the tumor changed. DESIGN: The expression of p53 protein was evaluated by immunohistochemical analysis (clone BP53-12-1; Bio-Genex, San Ramon, Calif). SETTING: Tertiary university medical center. INTERVENTION: Two to 3 courses of chemotherapy with paclitaxel and carboplatin. MAIN OUTCOME MEASURES: Pathologic complete remission or residual tumor. RESULTS: The results of p53 immunostaining were positive in 24 (67%) of 36 HNSCC specimens before chemotherapy. After chemotherapy, 8 patients achieved pathologic complete remission. Before chemotherapy, the tumor was p53 negative in 2 patients and positive in 6 patients. CONCLUSIONS: No correlation of p53 protein expression with response to chemotherapy was noted. The expression of p53 protein converted from positive to negative in 5 (42%) of 12 specimens from patients with residual tumor after chemotherapy, with no impact on clinical outcome.

Primary cutaneous angiotropic large-cell lymphoma in a patient with acquired immunodeficiency syndrome.

Patients with acquired immunodeficiency syndrome are at increased risk of developing malignant lymphoma, particularly of the large noncleaved, immunoblastic, and small noncleaved cell types. Angiotropic large-cell lymphoma, a relatively rare high-grade lymphoma, has not previously been described in the setting of acquired immunodeficiency syndrome. Because angiotropic large-cell lymphoma most commonly involves the skin and central nervous system, and because of its relative rarity, its presentation in the skin of a patient with acquired immunodeficiency syndrome may pose a diagnostic dilemma.

Large cell variants of CD5+, CD23- B-cell lymphoma/leukemia.

CONTEXT: Mantle cell lymphoma (MCL), and its leukemic phase, constitute a well-studied hematologic malignancy with known overall survival, prognostic indicators, morphologic findings at diagnosis and in bone marrow, and known incidence of the bcl-1 immunoglobulin gene rearrangement. Large cell variants of B-cell lymphoma/leukemia with a mantle cell immunophenotype (CD5+, CD23-), including but not limited to blastic MCL, prolymphocytoid MCL, blastic mantle cell leukemia, and prolymphocytic mantle cell leukemia, are not as well characterized. Although blastic MCL is known to be associated with a shorter overall survival than conventional MCL, the large cell variants of B-cell lymphoma/leukemia with a mantle cell immunophenotype have not been described as fully as conventional MCL. OBJECTIVE: The purpose of the present study was to describe the large cell variants of B-cell lymphoma/leukemia with a mantle cell immunophenotype. DESIGN: Nineteen cases of large cell variants of CD5+, CD23- B-cell lymphoma/leukemia are reviewed and described in regard to morphology, bone marrow morphological findings, Cyclin D1 immunostaining, and bcl-1 analysis. Clinical data were not available owing to the varied clinical sources of the specimens. SETTING: Tertiary-care academic institution. RESULTS: Lymph node involvement in blastic CD5+, CD23- B-cell lymphoma was diffuse (100%) with a nodular component (33%) or focal mantle zone pattern (10%). Bone marrow involvement in blastic CD5+, CD23- B-cell lymphoma was seen in only 27% of cases and was composed predominantly of small, slightly irregular lymphocytes. Cyclin D1 was demonstrated in 60% of the 15 cases analyzed and more sensitive in B5-fixed tissue. Bcl-1 (performed in 5 cases) was not detected in the 4 cases of blastic CD5+, CD23- B-cell lymphoma analyzed and was detected in the case of the prolymphocytoid MCL. Cyclin D1 was demonstrated in all 4 bcl-1 negative cases and was negative in the bcl-1 positive prolymphocytoid MCL. CONCLUSION: Careful analysis of clinical data, morphology, immunophenotype, Cyclin D1 expression, and molecular analysis are required to differentiate the unusual large cell variants of MCL from other processes.