Sustainable Development of Pathology in Sub-Saharan Africa: An Example From Ghana.

CONTEXT: - Pathology services are poorly developed in Sub-Saharan Africa. Komfo Anokye Teaching Hospital in Kumasi, Ghana, asked for help from the pathology department of the University Hospital of North Norway, Tromsø. OBJECTIVE: - To reestablish surgical pathology and cytology in an African pathology department in which these functions had ceased completely, and to develop the department into a self-supporting unit of good international standard and with the capacity to train new pathologists. DESIGN: - Medical technologists from Kumasi were trained in histotechnology in Norway, they were returned to Kumasi, and they produced histologic slides that were temporarily sent to Norway for diagnosis. Two Ghanaian doctors received pathology training for 4 years in Norway. Mutual visits by pathologists and technologists from the 2 hospitals were arranged for the introduction of immunohistochemistry and cytology. Pathologists from Norway visited Kumasi for 1 month each year during 2007-2010. Microscopes and immunohistochemistry equipment were provided from Norway. Other laboratory equipment and a new building were provided by the Ghanaian hospital. RESULTS: - The Ghanaian hospital had a surgical pathology service from the first project year. At 11 years after the start of the project, the services included autopsy, surgical pathology, cytopathology, frozen sections, and limited use of immunohistochemistry, and the department had 10 residents at different levels of training. CONCLUSIONS: - A Ghanaian pathology department that performed autopsies only was developed into a self-supported department with surgical pathology, cytology, immunohistochemistry, and frozen section service, with an active residency program and the capacity for further development that is independent from assistance abroad.

Plasma equol concentration is not associated with breast cancer and fibrocystic breast conditions among women in Shanghai, China.

Equol (a bacterial metabolite of the soy isoflavone daidzein) is produced by 30% to 50% of humans and may be associated with health outcomes. We hypothesized that plasma equol would be inversely associated with risks of fibrocystic breast conditions (FBC) and breast cancer (BC). Plasma from women in a breast self-examination trial in Shanghai with BC (n=269) or FBC (n=443), and age-matched controls (n=1027) was analyzed for isoflavones. Equol was grouped into categories (<20, 20-<45, and ≥45nmol/L) and, among women with daidzein ≥20nmol/L, the log10 equol:daidzein ratio was grouped into tertiles. Where available, non-cancerous tissue (NCT) adjacent to the carcinomas from women with BC were classified as non-proliferative or proliferative (n=130 and 172, respectively). The lesions from women with FBC were similarly classified (n=99 and 92, respectively). Odds ratios (OR) and 95% confidence intervals (CI) were calculated across equol categories and tertiles of log10 equol:daidzein ratio. Equol categories were not associated with FBC or BC (P>.05). For log10 equol:daidzein, compared to controls there were positive associations in the mid tertile for proliferative FBC (OR 2.06, 95% CI 1.08-3.93), BC with proliferative NCT (OR 2.95, 95% CI 1.37-6.35), and all BC regardless of histology (OR 2.37, 95% CI 1.43-3.95). However, trends in ORs with increasing plasma equol values or equol:daidzein ratios were not observed (P>.05). The results of this study do not provide evidence that equol plays a role in the etiology of these breast conditions. However, further work is needed to confirm or refute this conclusion.

No difference in the prevalence of benign breast changes between women from Ghana and Norway: an autopsy study.

Breast carcinoma develops gradually through multiple steps, some of which are recognizable as benign or premalignant histological changes. The age-standardized breast-cancer incidence rate is three times higher in Norway than in Ghana. A similar difference in the prevalence of benign and premalignant breast changes in the general populations would be expected if the difference in incidence rates were mainly due to cancer initiation factors, but not if it were caused by later stage promotion and progression factors. Breast tissue was taken by a standardized protocol from the autopsies of 44 Ghanaian and 26 Norwegian women between 15 and 60 years of age. Blind-labelled hematoxylin and eosin stained sections were examined independently by each of the three authors and the occurrence of histological changes in each section was recorded. The study revealed no significant difference between Norwegian and Ghanaian women in the prevalence of either proliferative or non-proliferative breast changes. The recorded incidence of breast cancer in Ghana may be under-estimated because of lower access to health services, lower patient awareness, and absence of population screening for breast cancer. Otherwise, the results support the conclusion that the lower incidence of breast cancer in Ghana than in Norway is mainly due to late-stage promotion and progression rather than initiation factors.

Hormone receptors and Her2 expression in breast cancer in sub-Saharan Africa. A comparative study of biopsies from Ghana and Norway.

Hormonal treatment of breast cancer is effective only in patients whose tumors express estrogen and/or progesterone receptors (ER, PR). Receptor assessment is often not available in low-resource areas, and the choice may be to apply endocrine therapy to all or none of breast cancer patients, depending on the proportion of patients that can be expected to respond. Fifty-one invasive breast cancers from Ghana and 100 from Norway diagnosed in the same laboratory during the same time period were reexamined in a blinded slide review. Of Ghanaian tumors, 76% were ER+ (≥1% ER+ tumor cells). Of Norwegian tumors, 85% were ER+. Triple-negative tumors were seen in 22% of Ghanaian patients and in 7% of Norwegian patients. A review of previous similar studies in sub-Saharan patients shows very discrepant results. Standardization and quality control of receptor assessment and well-designed clinical trials in sub-Saharan African breast cancer patients are needed to give a sound basis for endocrine treatment in this area.

[A man with persisting fever, night sweats and high sedimentation rate]. / En mann med vedvarende feber, nattesvette og høy senkningsreaksjon.

BACKGROUND: Fever of unknown origin and high sedimentation rate are common clinical problems. MATERIAL AND METHODS: A middle-aged man with fever of unknown origin, night sweats and high sedimentation rate was referred to our hospital for investigation. RESULTS AND INTERPRETATION: The patient was suspected to have mononucleosis or reactivation of infectious mononucleosis because of mild anaemia and thrombocytopenia, a weakly positive IgM antibody test for Epstein-Barr virus and monocytosis (in peripheral blood). Because monocytosis, elevated sedimentation rate and fever persisted, bone marrow smears were prepared and biopsies taken.The third biopsy showed that morphology was consistent with chronic myelomonocytic leukemia (CMML), which was confirmed by two later biopsies. However, a malignant cell population (consisting of blasts in peripheral blood) was only found in one of several flow cytometry assessments of peripheral blood and bone marrow aspirate and cytogenetic analyses of bone marrow cells were normal. The patient's clinical situation has been stable for some years and treatment has not been necessary.

Selected estrogen receptor 1 and androgen receptor gene polymorphisms in relation to risk of breast cancer and fibrocystic breast conditions among Chinese women.

BACKGROUND: Polymorphisms in sex hormone receptor-encoding genes may alter the activity of sex hormone receptors and thereby affect susceptibility to breast cancer and related outcomes. METHODS: In a case-control study of women from Shanghai, China, we examined the risk of breast cancer and fibrocystic breast conditions associated with the ESR1 PvuII (rs2234693) and XbaI (rs9340799) and AR CAG repeat ((CAG)(n)) and GGC repeat ((GGC)(n)) polymorphisms among 614 women with breast cancer, 467 women with fibrocystic conditions, and 879 women without breast disease. We also evaluated whether risk differed by the presence/absence of proliferative changes (in the extratumoral epithelium or fibrocystic lesion), menopausal status, or body mass index (BMI). Age-adjusted odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated using logistic regression. RESULTS: Only associations with AR (CAG)(n) and (GGC)(n) genotypes were detected. Allocating AR (CAG)(n) genotypes into six categories, with the (CAG)(22-24)/(CAG)(22-24) genotype category designated as the reference group, the (CAG)(>24)/(CAG)(>24) genotype category was associated with an increased risk of fibrocystic breast conditions (OR, 1.8; 95% CI, 1.1-3.0). Relative to the AR (GGC)(17)/(GGC)(17) genotype, the (GGC)(17)/(GGC)(14) genotype was associated with elevated risks of incident breast cancer (OR, 2.6; 95% CI, 1.3-5.4) and fibrocystic conditions (OR, 2.3; 95% CI, 1.1-4.5). Results did not differ according to proliferation status, menopausal status, or BMI. CONCLUSION: Although these data lend support for a link between AR variation and breast disease development, given the low frequency of the putative risk-conferring genotypes and other constraints, further confirmation of our results is needed.

Fruit and vegetable intakes are associated with lower risk of breast fibroadenomas in Chinese women.

Fibroadenomas are common benign breast conditions among women and account for approximately 50% of breast biopsies performed. Dietary factors are known to influence benign breast conditions in the aggregate, but little is known of their association specifically with fibroadenoma. Our objective in this study was to evaluate the association between dietary and other factors and fibroadenoma risk. A case-control study, nested in a randomized trial of breast self-examination (BSE) in Chinese textile workers in Shanghai, China, was conducted between 1989 and 2000. The study sample included 327 affected women and 1070 controls. Women were administered a FFQ and a questionnaire that elicited reproductive and gynecological history and other information. Odds ratios, as estimates of relative risks, were calculated using multivariate conditional logistic regression. Significant decreasing trends in risk of fibroadenoma were observed with intake of fruits and vegetables and with number of live births, and a reduced risk was also associated with natural menopause, oral contraceptive use, and moderate exercise (walking and gardening). Increased risk of fibroadenoma was associated with heavy physical activity in one's 20s, breast cancer in a first-degree relative, and a history of prior benign breast lumps; and significant increasing trends in risk were observed with numbers of BSE per year and years of education. In conclusion, a diet rich in fruits and vegetables and the use of oral contraceptives may reduce risk of fibroadenoma.

[50-year-old woman with elevated haemoglobin and iron deficiency]. / En 50 år gammel kvinne med høyt hemoglobinnivå og jernmangel.

BACKGROUND: Elevated haemoglobin and erythrocytosis are frequent causes for investigation. MATERIAL AND METHODS: A 50-year-old woman with elevated haemoglobin and erythrocytosis was referred to our hospital for investigation. RESULTS AND INTERPRETATION: She had elevated serum erythropoietin and iron deficiency. Mutational status of the JAK2 gene was negative with respect to polycythemia vera, and no secondary reasons for polycythemia - including tumours - were revealed. A bone marrow biopsy and bone marrow smear showed a moderately increased number of lambda- positive monoclonal plasma cells, and small amounts of lambda light chains were detected in the urine. Serum electrophoreses showed no gammopathy. The reason for her elevated haemoglobin could be an erythropoietin-producing tumour or an idiopathic erythrocytosis based on a mutation in exon 12 of the JAK2 gene. Investigation of her plasma cells revealed a 10-fold increase in erythropoietin mRNA expression, indicating the reason for her elevated serum erythropoietin and haemoglobin values.

Dietary and stored iron as predictors of breast cancer risk: A nested case-control study in Shanghai.

Increases in risk of breast cancer in successive generations of migrants to the United States from China and rapid temporal changes in incidence rates in China following social and economic changes clearly implicate environmental factors in the etiology of this disease. Case-control and cohort studies have provided evidence that at least some of these factors may be dietary. Iron, an essential element necessary for cell function, has also been demonstrated to have potential carcinogenic and co-carcinogenic activities. Iron overload, which was previously uncommon, has become more common in the United States than iron deficiency and may be increasing in China concurrently with dramatic increases in meat consumption. A case-control study nested in a cohort of women in Shanghai, China, was conducted to evaluate possible associations between risk of proliferative and nonproliferative fibrocystic changes as well as breast cancer and dietary iron intake and plasma ferritin levels. Plasma ferritin levels and reported dietary iron intake were compared in 346 women with fibrocystic changes, 248 breast cancer cases and 1,040 controls. Increasing ferritin levels were significantly associated with increasing risk of nonproliferative fibrocystic changes (OR: 2.51, 95% CI: 1.16-5.45, p trend = 0.04). Similar, but weaker, trends were observed for proliferative changes and for breast cancer. Risk of breast cancer relative to the risk of fibrocystic changes was associated with dietary iron intake in women with nonproliferative fibrocystic changes (OR: 2.63, 95% CI: 1.04-6.68, p = 0.02). In conclusion, this study finds significant associations between iron (stored and dietary) and fibrocystic disease and breast cancer.

Erythrocyte fatty acids and risk of proliferative and nonproliferative fibrocystic disease in women in Shanghai, China.

BACKGROUND: Although benign breast changes are more common than breast cancer, little evidence regarding risk factors for benign breast conditions is available. Omega-3 (n-3) fatty acids have antiinflammatory and antiproliferative actions and may be important in reducing the risk of benign conditions. There is a lack of research on the association of n-3 fatty acids with risk of benign fibrocystic breast changes. OBJECTIVES: The objectives of the study were to evaluate the role of n-3 and other fatty acids in the development of benign proliferative fibrocystic conditions (PFCs) and nonproliferative fibrocystic conditions (NPFCs) in the breast and to evaluate the progression of fibrocystic changes in breast cancer. DESIGN: We conducted a case-control study to determine erythrocyte fatty acid concentrations in 155 women with NPFCs, 185 women with PFCs, 241 women with breast cancer (127 with nonproliferative and 114 with proliferative changes in the noncancerous extratumoral mammary epithelium), and 1,030 control subjects. We estimated the relative risk of NPFCs, PFCs, and breast cancer with proliferative and nonproliferative changes in extratumoral tissue compared with the risk of these changes alone. RESULTS: Women in the highest quartile of eicosapentaenoic acid concentrations were 67% less likely to have an NPFC alone or with breast cancer and 49% less likely to have breast cancer than were women with PFCs. gamma-Linolenic acid (18:3n-6) was positively associated with all fibrocystic and cancerous conditions. Palmitic:palmitoleic acid (n-7 saturation index) was inversely associated with risk in all comparisons. CONCLUSION: Our results support a protective effects of n-3 fatty acid intake and the n-7 saturation index against benign fibrocystic breast changes and the progression of proliferative changes to breast cancer.

Genetic variation in CYP19A1 and risk of breast cancer and fibrocystic breast conditions among women in Shanghai, China.

CYP19A1 encodes for aromatase, which irreversibly converts androgens to estrogens; variation in this gene may affect individual susceptibility to breast cancer and other sex hormone-dependent outcomes. In a case-control study nested within a breast self-examination trial conducted in China, we examined whether CYP19A1 polymorphisms (rs1870049, rs1004982, rs28566535, rs936306, rs11636639, rs767199, rs4775936, rs11575899, rs10046, and rs4646) were associated with risk of breast cancer and fibrocystic breast conditions. Cases were diagnosed with breast cancer (n = 614) or fibrocystic breast conditions (n = 465) during 1989 to 2000. Controls were free of breast disease during the same period (n = 879). Presence of proliferative changes within the extratumoral tissue of women with breast cancer and the lesions of women with fibrocystic conditions only was assessed. None of the polymorphisms were associated with overall risk of breast cancer or fibrocystic breast conditions. Differences in breast cancer risk, however, were observed by proliferation status. The risk of breast cancer with (but not without) proliferative fibrocystic conditions was increased among women homozygous for the minor allele of rs1004982 (C), rs28566535 (C), rs936306 (T), and rs4775936 (C) relative to those homozygous for the major allele [age-adjusted odds ratios (95% confidence intervals), 2.19 (1.24-3.85), 2.20 (1.27-3.82), 1.94 (1.13-3.30), and 1.95 (1.07-3.58), respectively]. Also, haplotypes inferred using all polymorphisms were not associated with overall risk of either outcome, although some block-specific haplotypes were associated with an increased risk of breast cancer with concurrent proliferative fibrocystic conditions. Our findings suggest that CYP19A1 variation may enhance breast cancer development in some women, but further confirmation is warranted.

Guideline implementation for breast healthcare in low- and middle-income countries: diagnosis resource allocation.

A key determinant of breast cancer outcome in any population is the degree to which newly detected cancers can be diagnosed correctly so that therapy can be selected properly and provided in a timely fashion. A multidisciplinary panel of experts reviewed diagnosis guideline tables and discussed core implementation issues and process indicators based on the resource stratification guidelines. Issues were then summarized in the context of 1) clinical assessment, 2) diagnostic breast imaging, 3) tissue sampling, 4) surgical pathology, 5) laboratory tests and metastatic imaging, and 6) the healthcare system. Patient history provides important information for the clinical assessment of breast and comorbid disease that may influence therapy choices. Focused clinical breast examination and complete physical examination provide guidance on the extent of disease, the presence of metastatic disease, and the ability to tolerate aggressive therapeutic regimens. Breast imaging improves preoperative diagnostic assessment and also permits image-guided needle sampling. Diagnostic mammography was not considered mandatory in low- and middle-income countries when resources are lacking. Needle biopsy is preferred to surgical excision for the initial diagnosis of suspicious breast lesions, unless resources are unavailable. Mastectomy should never be used as a method of tissue diagnosis. The availability of predictive tumor markers, especially estrogen receptor testing, is critical when endocrine therapies are available; quality assessment of immunohistochemistry testing is important to avoid false-negative results. Incremental allocation of resources can help address economic disparities and help ensure equity in access to timely diagnosis.

Breast pathology guideline implementation in low- and middle-income countries.

The quality of breast healthcare delivery and the ultimate clinical outcome for patients with breast cancer are directly related to the quality of breast pathology practices within the healthcare system. The Breast Health Global Initiative (BHGI) held its third Global Summit in Budapest, Hungary from October 1 to 4, 2007, bringing together internationally recognized experts to address the implementation of breast healthcare guidelines for the early detection, diagnosis, and treatment in low-income and middle-income countries (LMCs). From this group, a subgroup of experts met to address the specific needs and concerns related to breast pathology program implementation in LMCs. Specific recommendations were made by the group and process indicators identified in the areas of personnel and training, cytology and histopathology interpretation, accuracy of pathology interpretation, pathology reporting, tumor staging, causes of diagnostic errors, use of immunohistochemical markers, and special requirements to facilitate breast conservation therapy. The group agreed that the financial burden of establishing and maintaining breast pathology services is counterbalanced by the cost savings from decreased adverse effects and excessive use of treatment resources that result from incorrect or incomplete pathologic diagnosis. Proper training in breast pathology for pathologists and laboratory technicians is critical and provides the underpinnings of programmatic success for any country at any level of economic wealth.

Re-establishing a surgical pathology service in Kumasi, Ghana: case report and discussion of barriers and key elements of a successful collaboration between low- and high-resource countries.

At Komfo Anokye Teaching Hospital (KATH) in Kumasi, Ghana, a breakdown of technical equipment and lack of pathologists resulted in closure of the surgical pathology laboratory in 2004. At an international meeting in January 2005, 1 USA and 1 Norwegian pathologist were asked if their departments could help with the pathology problem at KATH. This article describes the proposals, the barriers encountered, and the key elements of the final successful collaboration between a low-resource and a high-resource country. The proposal to the USA hospital focused on receiving specimens for diagnosis. A detailed proposal was not developed, as several key operational barriers were identified early on, including legal issues, technical capacity issues, and staff capacity issues. The proposal to the University Hospital of North Norway (UNN) resulted in development of a 5-year plan to reestablish surgical pathology at KATH. Two KATH technicians came to UNN and trained in the histopathology laboratory for 3 months. On their return, they started producing slides at KATH. Since April 2006, weekly shipments of hematoxylin and eosin (H & E) stained slides have been sent to UNN by courier service. When needed, paraffin blocks are sent on request. In March 2006, 2 young Ghanaian physicians were received as trainees at the UNN to do full resident work and training with the aim of being approved as specialists in pathology in Ghana by 2010. Full surgical pathology service and training of new pathologists on site are expected to be reestablished at KATH by 2010.

Polymorphisms in steroid hormone biosynthesis genes and risk of breast cancer and fibrocystic breast conditions in Chinese women.

Common variants in genes encoding for key enzymes involved in steroidogenesis may alter sex steroid hormone levels, thereby influencing susceptibility to breast carcinoma and related conditions. In a case-control study of Chinese women, we examined genotypes of the CYP11A1 pentanucleotide [(TAAAA)n] repeat (D15S520), CYP17A1 rs743572, and HSD17B1 rs605059 polymorphisms in relation to the risk of breast cancer and fibrocystic breast conditions, comparing 615 women with breast cancer and 467 women with fibrocystic breast conditions separately with 879 women without clinical breast disease. We also evaluated whether these relationships differed by the presence of proliferation in the extratumoral epithelium or fibrocystic lesions, menopausal status, or body mass index. Only CYP11A1 genotype was related to breast cancer risk, with women homozygous for the 4-repeat allele, relative to those homozygous for the 6-repeat allele, at reduced risk (age-adjusted odds ratio, 0.58; 95% confidence interval, 0.37-0.91). There was some suggestion of a stronger inverse association for breast cancer with evidence of proliferation in the extratumoral epithelium than for breast cancer without extratumoral proliferation. Breast cancer risk associated with CYP11A1 genotype did not differ by menopausal status or body mass index level. No associations between CYP11A1, CYP17A1, and HSD17B1 genotypes and risk of fibrocystic breast conditions were observed. Our findings support the possibility that common allelic variation at the CYP11A1 D15S520 locus alters breast cancer risk in Chinese women.

Glutathione S-transferase M1 and P1 polymorphisms and risk of breast cancer and fibrocystic breast conditions in Chinese women.

Enzymes encoded by the glutathione S-tranferase mu 1 (GSTM1) and pi 1 (GSTP1) genes, which are expressed in breast tissue, catalyze the detoxification of endogenous and exogenous electrophiles. Reduced enzyme activity, due to carriage of the GSTM1 deletion or the GSTP1 Ile105Val Val allele, may therefore affect susceptibility to breast cancer and related conditions. In a case-control study of Chinese women, we examined whether these polymorphisms were associated with risk of breast cancer and fibrocystic breast conditions. Women diagnosed with breast cancer (n=615) or fibrocystic breast conditions (n=467) were compared to women without clinical breast disease (n=878). We also examined whether these associations differed by menopausal status or by presence of proliferation in the extra-tumoral epithelium among women with breast cancer and in lesions among women with fibrocystic conditions. No overall association of either GST polymorphism with risk of breast cancer or fibrocystic breast conditions was observed. There was some evidence of slightly elevated cancer risk associated with carriage of the GSTM1 null genotype and at least one GSTP1 105-Val allele (OR=1.33, 95% CI, 0.99-1.80), compared to carriage of the GSTM1 non-null and GSTP1 Ile/Ile genotypes. This relationship was stronger in women who had breast cancer with extra-tumoral tissue proliferation (OR=1.77, 95% CI, 1.03-3.04). Our results suggest that GSTM1 and GSTP1 genotypes do not individually influence susceptibility to breast cancer or fibrocystic breast conditions. The observed increased risk of breast cancer associated with joint carriage of the GSTM1 null genotype and GSTP1 105-Val allele needs confirmation in other studies.

Plasma isoflavones and fibrocystic breast conditions and breast cancer among women in Shanghai, China.

BACKGROUND: Proliferative benign breast conditions are associated with elevated risk of breast cancer, whereas nonproliferative conditions are not strongly associated with risk. Factors acting before onset of hyperplasia might be associated with both benign conditions and breast cancer, whereas those on the proliferative disease-to-cancer pathway would be associated only with cancer. Soy isoflavone exposure may influence breast cancer risk, but little is known of its association with benign conditions. MATERIALS AND METHODS: We examined possible relationships between plasma genistein and daidzein concentrations and risk of breast disease in women, in a breast self-examination trial in Shanghai, China, diagnosed with breast cancer (n = 196) or a benign breast condition (n = 304), and 1,002 age-matched controls with no known breast disease. Benign conditions were classified as nonproliferative (n = 131) or proliferative with or without atypia (n = 173). RESULTS: Isoflavone concentrations were inversely associated with risk of nonproliferative and proliferative benign fibrocystic conditions, as well as with breast cancer, both with and without concomitant proliferative changes in ipsilateral noncancerous mammary epithelium (P(trend) < 0.01 for all comparisons with controls). Women in the highest quartile of plasma genistein (>76.95 ng/mL) were less likely to have breast cancer (odds ratio, 0.26; 95% confidence interval, 0.13-0.50) or benign conditions (odds ratio, 0.40; 95% confidence interval, 0.23-0.70) compared with women in the lowest quartile (<9.42 ng/mL). Observed risks for breast cancer with and without surrounding proliferative changes were not different, respectively, from observed risks for benign proliferative and nonproliferative conditions alone. CONCLUSION: Isoflavone exposure was inversely associated with fibrocystic breast conditions and breast cancer, and the results suggest that effects on cancer risk occur early in carcinogenesis.

[50-year-old man with fatigue and monoclonal gammopaty]. / 50 år gammel mann med slapphet og monoklonal gammopati.

This article presents an extremely rare case of monoclonal gammopathy of undetermined importance (MGUS) (known for 16 years) that progressed to multiple myeloma during cytotoxic treatment of malignant lymphoma. Morphological and immunochemical studies were used to characterize the two blood diseases. Identification of type 2 (malignant lymphoma) and type 1(multiple myeloma) disease indicate that the condition was biclonal. The malignant lymphoma responded completely to treatment with chlorambucil and the multiple myeloma responded partially to treatment with melphalan and prednisolone some months later. Diagnosis and follow up of MGUS is commented on.