Increased splanchnic blood flow after hypoglycaemia in diabetic and normal man: evidence against glucagon as a mediator

Analysis of non-Hodgkin lymphoma (NHL) involvement of bone marrow trephine biopsy specimens by morphologic features and immunohistochemistry is often difficult, and the criteria for involvement are ill defined. We compared the morphologic and immunohistochemical analysis of B-cell NHL involvement with immunoglobulin heavy chain gene (IgH) rearrangement analysis by polymerase chain reaction (PCR) amplification of the complementarity determining region 3 (CDR3) in bone marrow biopsy specimens from patients with mantle cell lymphoma (n = 53) or hairy cell leukemia (n = 71). By combing morphologic features and phenotype, 54 specimens were considered positive, 62 negative, and 8 inconclusive. PCR analysis showed clonal IgH rearrangements in 46 positive and 6 inconclusive specimens. No clonal IgH rearrangements were present in 61 negative specimens. The 1 false-positive and most false-negative PCR results were likely due to sampling error or DNA degradation of the fixed tissues. In most cases, bone marrow involvement by NHL can be identified by histologic and immunohistochemical examination. Furthermore, clonality of the B-cell population can be detected by amplification of the IgH CDR3 on DNA extracted from bone marrow trephine biopsy sections, which can be helpful in cases diagnosed as inconclusive.     

Immunohistochemistry in apparently normal bone marrow trephine specimens from patients with nodal follicular lymphoma

AIM: To establish the role of immunohistochemistry (using a limited panel of antibodies) in detecting minimal involvement by follicular lymphoma in routinely processed bone marrow trephine specimens, which show no obvious morphological (light microscopic) evidence of lymphoma; to determine whether bcl-2 immunostaining in bone marrow distinguishes between benign and malignant infiltrates in a patient with nodal follicular lymphoma. METHODS: Twenty seven consecutively selected paraffin wax embedded, formalin fixed bone marrow trephine specimens were stained with the following antibodies: anti-bcl-2, anti-CD79a, anti-CD3, and kappa and lambda light chains, using the Streptavidin biotin complex technique. RESULTS: Five of the 27 cases, which showed no evidence of involvement by follicular lymphoma on routine stains, showed monotypic B cells on immunohistochemistry. Two of the cases were diffuse, while the remaining three showed mini-aggregates around bony trabeculae. In all five cases the lymphomatous infiltrates were strongly bcl-2 positive. Reactive B lymphoid nodules did not show the same degree of bcl-2 positivity, and negative cells could be discerned within the reactive nodules. CONCLUSIONS: There is merit in studying so-called negative bone marrows immunohistochemically in order to detect minimal involvement by follicular lymphoma. A limited panel of antibodies including anti-bcl-2, anti-CD79a and anti-CD3 is usually adequate to accomplish this. Strongly bcl-2 positive lymphoid aggregates in the bone marrow of patients with nodal follicular lymphoma are indicative of lymphoma.     

Pre-operative assessment of cardiac risk for non-cardiac surgery

We describe the cases of two patients who presented with granulocytic sarcoma with mediastinal involvement 15 and 21 months before development of acute myeloid leukemia. In both cases several bone marrow aspirates and trephine biopsy specimens, obtained at presentation and subsequently, revealed no evidence of leukemic infiltration. One case was originally misdiagnosed as large-cell non-Hodgkin's lymphoma, which resulted in inappropriate therapy. In both cases immunohistochemical staining revealed that tumor cells were positive for leucocyte common antigen but not for conventional B- or T-lymphoid-cell markers. Retrospective analysis revealed that tumor cells in both cases were positive for myeloid markers. Histopathologists should be aware that granulocytic sarcoma may occur in unusual extramedullary sites without evidence of bone marrow involvement. If inappropriate treatment is to be avoided, a diagnosis of granulocytic sarcoma should be considered when hemopoietic tumor cells do not stain with conventional antibodies against B- and T-lymphoid cells. Both histochemical and immunohistochemical staining should be performed in such cases to determine whether the cells are of myeloid lineage. A diagnosis of granulocytic sarcoma is not ruled out when bone marrow biopsy specimens show no evidence of leukemic infiltration.     

系统性间变性大细胞淋巴瘤骨髓累及的临床病理学研究

目的 探讨系统性间变性大细胞淋巴瘤(S-ALCL)骨髓累及的临床病理学特点、免疫学表型及临床生物学行为.方法 回顾性分析34例S-ALCL病例资料,进行骨髓活检(19例)或涂片(15例).其中ALK(+)24例,ALK(-)10例.HE染色、免疫组织化学染色观察病理形态及免疫表型,原位杂交法检测EB病毒.结果 6例(17.6%)S-ALCL存在骨髓累及,均经骨髓活检标本确定,15例患者骨髓涂片中均未见肿瘤累及.ALK(+)ALCL和ALK(-)ALCL骨髓累及的发生率分别为16.7%(4/24)和20.0%(2/10),差异无统计学意义(P=0.3555).与无骨髓累及病例比较,骨髓累及病例的年龄、性别分布差异无统计学意义(P值分别为0.8089和0.3085).骨髓累及者肿瘤细胞以间质性分布为主[83.3%(5/6)].生存分析统计提示伴有骨髓累及的患者预后明显差于无骨髓累及者(P=0.0407).结论 S-ALCL骨髓累及发生率低,与患者的发病年龄、性别及ALK蛋白的表达无相关性.伴有骨髓累及的S-ALCL患者临床预后差,骨髓活检在判断S-ALCL预后中有重要意义.     

Leukemic phase of mantle cell lymphoma presenting as anemia: diagnosis by combining flow cytometry and cytomorphology

We report a case of mantle cell lymphoma in leukemic phase, which was diagnosed by a bone marrow biopsy performed as part of a workup for chronic anemia in a patient without lymphadenopathy. The patient, a 79-year-old man with diabetes mellitus, hypertension, chronic renal failure, congestive heart failure, and atherosclerosis, presented with claudication. On admission, he also had an 8-month history of anemia, during which time he experienced a 18-kg weight loss. On presentation, the patient had normal vital signs, anemia, leukocytosis (as well as an absolute lymphocytosis), and splenomegaly; as mentioned, lymphadenopathy was absent. A bone marrow biopsy showed an increase in small to intermediate-sized, slightly irregular lymphocytes in interstitial nodules. Flow cytometric immunophenotyping of the bone marrow identified a monoclonal population of cells, representing 25% of cells within the bone marrow, with expression of CD19, CD20, immunoglobulin M/D, lambda light chain, HLA-DR, and CD5; reactions for CD10 and CD23 were absent. Based on morphologic and immunophenotypic analysis of the bone marrow, as well as morphologic review of the peripheral blood smear, a diagnosis of mantle cell lymphoma involving the bone marrow and in leukemic phase was made. Subsequent polymerase chain reaction analysis of DNA from peripheral blood identified a population of cells with the bcl-1 rearrangement. This case is unique in that the diagnosis of mantle cell lymphoma was made without lymph node or spleen analysis and the patient, although exhibiting bone marrow and peripheral blood involvement by mantle cell lymphoma at presentation, did not have lymphadenopathy.     

Bone marrow involvement in lymphoblastic lymphoma and small non-cleaved cell lymphoma: the role of trephine biopsy

Trephine biopsy (TB) combined with bone marrow aspiration (BMA) is the most common method for evaluating bone marrow (BM) involvement in non-Hodgkin's lymphomas. Nevertheless, the role of TB in high-grade lymphomas remains controversial. We reviewed the results of 42 consecutive BMAs and TBs performed simultaneously in 29 patients with lymphoblastic lymphoma (LL) and small, non-cleaved cell lymphoma (SNCL). In LL, 8M involvement was documented in 35.4% of the cases by BMA and 22.5% of the cases by TB. In SNCL it was documented in 45.4% of the cases by BMA and 36.3% by TB. There were no statistically significant differences (p > 0.05) in the rates of BM involvement found by TB or BMA in the two types of lymphoma, although BMA appeared to be more sensitive than TB. These observations suggest that routine TB may not be necessary in assessing BM involvement in patients with LL and SNCL.     

Pregnancy and lactation in homozygous beta-thalassemia major

Ki-1 anaplastic large cell lymphoma is a well-described subtype of non-Hodgkin's lymphoma with distinctive characteristics from the cytological, immunohistochemical and clinical points of view. One of the clinical behavior characteristic is that it rarely evolves into a leukaemic phase. We report the case of a 72-year-old man in which the appearance of tumor cells in peripheral blood was one of the most revealing information. The patient showed B-symptoms, bicytopenia and bone marrow involvement, together with hepatosplenomegaly and right axilar adenopathy, which after biopsied lead to Ki-1 anaplastic large cell lymphoma's diagnosis (stage IV-B). As far as the treatment and evolution are concerned, we choose a polychemotherapy (ACOP-B) because of the patient's age. Up to now clinical and analitical course is excellent and the patient is now in remission.     

ALK gene products in anaplastic large cell lymphomas and Hodgkin's disease

The translocation t(2;5)(p23;q35), discovered in CD30+ anaplastic large cell (ALC) lymphomas, creates a potentially oncogenic fusion gene, part of which is contributed by a novel tyrosine kinase, ALK. Absence of ALK expression from normal hematolymphoid cells provides a basis for the morphologic assessment of t(2;5). The distribution of the t(2;5) in ALC lymphomas and Hodgkin's disease (HD), as assayed by nonmorphologic methods, is controversial. We used in situ hybridization and/or immunohistology to show ALK gene products in 85 ALC lymphomas, 82 HD cases, 40 other lymphoproliferations, as well as in 6 HD- and 4 ALC lymphoma-derived cell lines. ALK gene products were restricted to t(2;5)-positive ALC lymphoma cell lines and tumor cells of 16 primary non-B cell, common-type ALC lymphomas. These were mainly from young patients with initial lymphonodal disease. ALK expression was not detectable in any other specimen, including all cases of HD and HD-like type ALC lymphoma as well as secondary ALC lymphomas. Full congruence was noted for labeling results obtained with both methods. In agreement with cytogenetic analyses, but at variance with recently published studies, ALK gene expression distinguishes a subset of ALC lymphomas from other CD30+ lymphomas, including HD. The results do not support concepts attributing a significant role to the t(2;5) in the development of HD.     

Recurrence with histological transformation 40 days after autologous peripheral blood stem cell transplantation (APBSCT) for cutaneous CD30-negative large T cell lymphoma

Localized cutaneous nontender nodules appeared on the back of a 52-year-old Japanese woman. Skin biopsy revealed atypical large T-lymphocytes infiltrating the dermis. CD30 staining was negative in tumor cells. The diagnosis was CD30-negative cutaneous large T cell lymphoma. There was no evidence of peripheral lymphadenopathy or bone marrow involvement. Six cycles of induction chemotherapy were administered and a complete clinical remission (CCR) was attained. Local irradiation was not given. As the clinical course of CD30-negative cutaneous large T cell lymphoma is recurrent and often incurable with conventional chemoradiotherapy, she received high-dose chemotherapy without total body irradiation (TBI) followed by unpurged autologous peripheral blood stem cell transplantation (APBSCT). A relapse in the skin followed 40 days after APBSCT, but tumor cells transformed into a CD30-positive anaplastic large cell lymphoma (ALCL). We question the need for TBI in conditioning and for purged stem cells for APBSCT in patients with high risk cutaneous lymphomas.     

An overview of rheumatological research in the European Union

We describe a case of a 73-year-old male with a rare T-cell lymphoma that presented deceptively as progressive hepatic failure with fever, weight loss, pancytopenia, mental confusion, splenomegaly, and no lymphadenopathy. An alcoholic history supported the diagnosis of cirrhosis, but a liver biopsy was not performed. A bone marrow biopsy was considered unremarkable. Death occurred after a course of four months. Postmortem examination showed hepatic, splenic, lymph node, and marrow infiltration by characteristically sparse, isolated, bizarre, medium-to-large sized neoplastic cells with extensive hepatic centrilobular necrosis, steatosis, and predominant splenic involvement. Immunohistochemical markers indicated a T-cell lymphoma consistent with either an alpha/beta peripheral T-cell lymphoma or a gamma/delta lymphoma. Definitive immunotyping was not available. However, the pathologic features are most consistent with a gamma/delta T-cell lymphoma. This case is an example of a rare, rapidly progressive lymphoma, which is a recognized clinical entity, easily missed, and treatable. Its diagnostic consideration must be explicitly communicated to pathologists, because the isolated or sparse tumor cells in a lymph node, liver, or bone marrow biopsy may easily be mistaken for variants of megakaryocytes or histiocytes.     

Indium bone marrow scintigraphy as an aid in selecting marrow biopsy sites for the evaluation of marrow elements in patients with lymphoma

One hundred and two previously treated lymphoma patients were studied with 111Indium bone marrow scans and bone marrow biopsies. The biopsies were considered to represent sampling errors when the cellularity of the biopsy did not reflect the general state of the marrow organ cellularity as demonstrated by the scan. In each instance the accuracy of the scan was confirmed by either another biopsy or the subsequent clinical course of the patient. Sampling errors were infrequent (1/51) in patients with normal peripheral blood counts and whose marrow had never been involved with tumor. Errors were especially likely (17/51) in patients who had had marrow involvement or those who had anemia, leukopenia, or thrombocytopenia. The 111Indium bone marrow scan allows the clinician to avoid selecting a biopsy site with a high risk for sampling error.     

Emergency medical services in mass gatherings: the experience of the Formula 1 Grand Prix ''San Marino'' in Imola

Autologous transplantation for non-Hodgkins lymphoma and Hodgkin's disease is widely used as standard therapy for those with high-risk or relapsed tumor. Peripheral blood stem cell (PBSC) collections have nearly completely replaced bone marrow stem cell (BMSC) harvests because of the perceived advantages of more rapid engraftment, less tumor contamination in the inoculum, and better survival after therapy. The advantage of PBSC, however, may derive from the hematopoietic stimulating cytokines used for PBSC mobilization. Therefore, we tested a randomized comparison of GM-CSF vs. G-CSF used to prime either BMSC or PBSC before collection for use in autologous transplantation. Sixty-two patients receiving transplants (31 PBSC; 31 BMSC) for non-Hodgkin's lymphoma (n = 51) or Hodgkin's disease (n = 11) were treated. All patients received 6 days of randomly assigned cytokine. Those with cellular marrow in morphologic remission underwent BMSC harvest, while those with hypocellular marrow or microscopic marrow tumor involvement had PBSC collected. Neutrophil recovery was similarly rapid in all groups (median 14 days; range 10-23 days), though two patients had delayed neutrophil recovery using GM-CSF primed PBSC (p = 0.01). Red cell and platelet recovery were significantly quicker after BMSC mobilized with GM-CSF or PBSC mobilized with G-CSF. This speedier hematologic recovery resulted in earlier hospital discharge as well. However, in multivariate analysis, neither the stem cell source nor randomly assigned G-CSF vs. GM-CSF was independently associated with earlier multilineage hematologic recovery or shorter hospital stay. Relapse-free survival was not independently affected by either the assigned stem cell source or the randomly assigned priming cytokine, though malignant relapse was more frequent in those assigned to PBSC (RR of relapse 3.15, p = 0.03). These data document that BMSC, when collected following cytokine priming, can yield a similarly rapid hematologic recovery and short hospital stay compared with cytokine-primed PBSC. Using primed BMSC, no difference in malignant relapse or relapse-free survival was observed. These findings suggest that despite widespread use of PBSC for transplantation, BMSC, when collected following hematopoietically stimulating cytokines, may remain a satisfactory source of stem cells for autologous transplantation. G-CSF and GM-CSF are both effective in priming autologous PBSC or BMSC for collection.     

Bone marrow biopsy in the diagnosis of fever of unknown origin in patients with acquired immunodeficiency syndrome

BACKGROUND: Fever is commonly observed in patients with human immunodeficiency virus (HIV) disease and frequently eludes diagnosis. The role of bone marrow biopsy in the diagnosis of fever of unknown origin in patients infected with HIV remains controversial. PATIENTS AND METHODS: One hundred twenty-three consecutive patients with 137 episodes of fever lasting 10 or more days without diagnosis after 1 week of hospitalization were evaluated by bone marrow biopsy. RESULTS: Overall, a specific diagnosis was achieved in 52 episodes by means of culture and histopathological examination (diagnostic yield, 37.9%). Three types of disease were found: mycobacterial infections (n = 36, 69% of documented episodes), including 18 patients with disseminated tuberculosis and 14 with Mycobacterium avium-intracellulare complex infections; non-Hodgkin lymphomas (n = 12, 23%); and visceral leishmaniasis (n = 4, 8%). Although bone marrow cultures were more sensitive than microscopic examination with special stains for the diagnosis of mycobacterial infections, the pathological examination of bone marrow led to a more rapid diagnosis of disease. In addition, the histopathological examination of bone marrow alone led to the diagnosis of a specific condition in 43 episodes (31.3% of all episodes). CONCLUSIONS: Bone marrow biopsy is a useful procedure for the diagnosis of fever in patients with advanced HIV disease, particularly in areas where tuberculosis and leishmaniasis are prevalent. Involvement of the marrow may be the first indication of the existence of extranodal non-Hodgkin lymphoma. For Mycobacterium avium-intracellulare complex infection, blood cultures were more sensitive than bone marrow biopsy.     

Value of bone marrow biopsy in the diagnosis of amyloidosis

Amyloid involvement of the bone marrow is not commonly diagnosed before necropsy. Paraffin sections of the trephine bone biopsy specimen are superior to marrow aspiration cell smears for the antemortem diagnosis. Thirteen cases of amyloidosis were diagnosed from the bone biopsy specimen during a ten-year period. Amyloid was detected in only two of the corresponding aspirates. Three morphologic patterns of marrow involvement were found: vascular, focal extravascular/perivascular, and diffuse. Five (38%) of the cases were associated with multiple myeloma. An abnormal immunoglobulin was detected in the serum or urine or both in ten of 11 cases when determined. Although the bone marrow may not be the best site for the diagnosis of amyloidosis, it should not be neglected and marrow biopsies taken for other diagnostic reasons may "incidentally" reveal amyloid. Amyloidosis should be included in the list of non-primary hematologic conditions of the bone marrow in which the trephine biopsy may prove useful for diagnosis.     

P9 in median nerve SEPs is a junctional potential generated by the change of the volume conductor size between trunk and neck

We report the case of a 78-year-old man in whom routine physical examination revealed cervical adenopathy and splenomegaly. Peripheral blood showed a normal white blood cell count with an absolute lymphocytosis, which included a population with slightly indented nuclei. Lymph node biopsy showed morphology compatible with mantle cell lymphoma. Bone marrow biopsy showed replacement by a lymphoid proliferation composed of lymphocytes with features similar to those found in the peripheral blood. Immunophenotypic analysis of both peripheral blood and lymph node showed positivity for CD19, CD20 and CD22, with lambda light chain restriction. Tests for CD5 and CD10 were negative. Cytogenetic analysis and polymerase chain reaction studies confirmed the presence of t(11,14) supporting a diagnosis of mantle cell lymphoma. This unusual case of CD5-negative mantle cell lymphoma exemplifies the importance of combined molecular, cytogenetic, and morphologic evaluation when confronted with a lymphoma having an atypical phenotype.     

Immunohistochemical detection of tumor cells in the bone marrow of breast cancer patients

BACKGROUND: Contamination of bone marrow and peripheral blood stem cells with tumor cells is a problem that may be encountered when autologous hematopoietic stem cell transplantation is conducted concurrently with high-dose chemotherapy. METHODS: Using monoclonal antibodies to a variety of tumors, the detection of tumor cells in the bone marrow of breast cancer patients was studied by immunohistochemistry. RESULTS: KL-1 and CAM5.2 were strongly reactive with breast cancer cells, but not with normal bone marrow cells. The reactivity of the tumor cells with EMA was not strong, and DF-3 and 115D8 yielded only slightly positive reactions. These latter antibodies also exhibited some reactivity to normal bone marrow cells. When tumor cells were admixed with normal cells, the sensitivity of CAM5.2 and EMA permitted the detection of one cell in 10(4), but with KL-1, the detection of one in 10(5) cells was possible. When immunohistochemical staining was used in testing 40 patients with advanced or recurrent breast cancer, positive reactions were obtained in four of 27 patients (14.8%) with KL-1, four of 26 (15.4%) with CAM5.2, and nine of 37 (23.7%) with KL-1 + CAM5.2, figures similar to those reported by others who studied stage IV patients. CONCLUSIONS: Immunohistochemical staining with KL-1 and CAM5.2 is therefore considered to be a useful technique for detecting contamination by tumor cells.     

Cytolytic activity of peripheral blood blast cells from patients with acute myeloid leukemia

The results of the present study demonstrate that cells with the morphologic and phenotypic characteristics of blast cells that are obtained from the peripheral blood of patients with newly-diagnosed or recurrent acute myeloid leukemia (AML) can be stimulated by gamma interferon + lipopolysaccharide (IFN/LPS) to mediate in vitro cytolysis of an NK-insensitive hepatoma cell line. The conditions of IFN/LPS induction and subsequent assessment of cytotoxicity that were employed were identical to those used conventionally to test macrophage-mediated tumor cell cytotoxicity. What was totally unexpected was that these same blast cells, in the absence of stimulation with IFN/LPS, were also found to mediate high levels of spontaneous cytotoxicity against autologous bone marrow cells and against the U937 human promonocytic leukemia cell line in vitro. This high level of spontaneous cytotoxicity against autologous bone marrow or U937 promonocytic leukemia cells was not enhanced by IFN/LPS or MCSF under conditions that stimulated cytotoxic function in normal blood monocytes and was markedly reduced by pretreatment of the blast cells with IL2 under conditions that induced potent NK/LAK-mediated cytotoxicity. Neutralizing antibodies against TNFalpha and/or IL1alpha/beta eliminated the cytolytic function of blast cells against autologous bone marrow or U937 promonocytic leukemia targets. These findings demonstrate the existence of a population of cells with the morphologic characteristics of blast cells in the peripheral blood of AML patients which has the capacity to mediate spontaneous cytolysis of autologous bone marrow cells or a promonocytic leukemia cell line. These cells may be an immature variant of normal precursors produced as a consequence of the disordered hematopoietic environment in the marrow of AML patients. Alternatively, this function may be mediated by a subset of the leukemic blasts themselves.     

Bone marrow transplantation for non-Hodgkin's lymphoma: a review

High dose chemotherapy and stem-cell rescue (bone marrow transplantation) is used increasingly in the treatment of malignant disorder. Numerous trials have demonstrated the effectiveness of bone marrow transplantation in the treatment of non-Hodgkin's lymphoma. However, there are many unanswered questions as to the role of high-dose therapy in certain subtypes of lymphoma, the timing of transplant, and even the type of transplant to perform. An attempt will be made to clarify many of these unanswered questions. The utilization of high-dose therapy for non-Hodgkin's lymphoma is recommended for most patients who have relapsed after initial therapy. Transplantation in first remission is not recommended routinely. Allogeneic bone marrow transplantation should by reserved for individuals with poorly responding disease or in individuals with bone marrow involvement. The precise roles of purging and transplantation of individuals with low grade lymphoma are being investigated.     

Granulocytic sarcoma of the female genital tract: a clinicopathologic study of 11 cases

Eleven patients, 13 to 76 (mean, 40) years of age, had granulocytic sarcoma of the female genital tract (FGT) (ovary, seven cases; vagina, three cases; cervix, one case). In nine cases, the FGT involvement was the initial clinical presentation of the disease, and in the other two cases, the FGT involvement was discovered during a relapse of acute myeloid leukemia. The tumors ranged from 0.5 to 14 (mean, 7.5) cm in greatest dimension. Two ovarian tumors were bilateral, and three were green. Microscopic examination revealed a predominantly diffuse pattern of growth, but cords and pseudoacinar spaces were also present focally in several cases. Sclerosis was seen in five tumors and was prominent in one. Prominent myeloid differentiation was readily recognizable on routinely stained sections in three cases, whereas the neoplastic cells in the other cases were primitive with only rare eosinophilic myelocytes. All 11 tumors were positive for chloroacetate esterase, nine of nine were strongly and diffusely positive for lysozyme, eight of eight for myeloperoxidase, seven of seven for CD68, and six of six for CD43. Examination of bone marrow or peripheral blood performed after the diagnosis of FGT involvement revealed acute myeloid leukemia in three of five cases. Two of these patients died of disease, 1 and 16 months after the initial diagnosis, and the third, who received chemotherapy, is alive and free of disease 8 months after the initial diagnosis. One of the two patients with negative bone marrow had recurrent granulocytic sarcoma 30 months after diagnosis and died of sepsis 1 month later; no residual disease was noted at autopsy. The other patient is alive and free of disease 18 months after the diagnosis. One of the four remaining patients with primary FGT involvement who did not have a bone marrow biopsy died of leukemia 24 months later; no follow-up information is available for the other three patients. One of the two patients with a prior diagnosis of acute myeloid leukemia was alive with disease 26 months later; follow-up is not available for the second patient. The diagnosis was often difficult in these cases, the most common problem being distinction from malignant lymphoma, but carcinoma, granulosa cell tumor, and, rarely, other tumors were considered. Immunohistochemical and enzyme histochemical staining were useful in establishing the diagnosis, although suspicion of the diagnosis on examination of routinely stained sections was of paramount importance.