Diabetic Mastopathy: A Case Report and Literature Review

Diabetic mastopathy is a rare fibroinflammatory breast disease characterized by lymphocytic lobulitis, ductitis, and perivasculitis with stromal fibrosis. This lesion often presents as a discretely palpable uni- or bilateral mass in long-standing type I diabetes and other autoimmune diseases. We report a case of insulin-dependent diabetic mastopathy, which presented clinically as an indeterminate breast lump suspicious for malignancy. The patient is a 36-year-old woman who had type 1 insulin-dependent diabetes mellitus. Mammography and ultrasonography raised a suspicion of malignancy, and an excisional biopsy was performed. A previous biopsy had shown no evidence of malignancy. Histopathological examination now showed dense keloid-like stromal fibrosis with epithelioid-like and spindly myofibroblasts and a characteristic lymphocytic infiltration around blood vessels in and around lobules and ducts, features consistent with diabetic mastopathy. The literature is briefly reviewed.Key Words: Diabetic mastopathy, Insulin-dependent, Breast cancer, Pseudomalignancy     

An uncommon case of diabetic mastopathy in type II non-insulin dependent diabetes mellitus

Diabetic mastopathy is an uncommon tumor-like proliferation of fibrous tissue of the breast that usually occurs in a patient who has suffered from type I diabetes mellitus of long duration. Here we report a rare case of diabetic mastopathy that occurred in type II non-insulin dependent diabetes mellitus. This patient was a 63-year-old postmenopausal woman. Mammography, ultrasonography and MR imaging could not distinguish it from breast cancer. Although the core needle biopsy specimen showed fibrosis without evidence of malignancy, excisional biopsy was performed. Histological findings demonstrated typical diabetic mastopathy with keloid-like fibrosis, perivascular lymphocytic infiltration, and lymphocytic lobulitis without evidence of malignancy. These lymphocytes were composed predominantly of B-cells. Five months after surgical biopsy, a nodular formation approximately 4 cm in diameter recurred adjacent to the resected end of the biopsy.     

Diabetic mastopathy: a case report with reference to the findings of enhanced computed tomography

We report a case of insulin-dependent diabetic fibrous mastopathy with special reference to the findings of computed tomography (CT). The patient was a 27-year-old woman with a history of insulin-dependent diabetes mellitus from childhood who presented with a right breast tumor. Physical examination showed a stony-hard, ill-defined but freely movable mass under the nipple of the right breast without nipple discharge. Mammography revealed a high-density mass shadow without microcalcifications or spicular formation. Ultrasonographic examination revealed an irregularly-shaped hypoechoic lesion with marked posterior acoustical shadowing. Contrast-enhanced CT revealed poor early phase contrast enhancement and slight delayed phase heterogeneous enhancement. Since core needle biopsy revealed fibrocystic disease, the lesion was suspicious for diabetic mastopathy. Incisional biopsy of the right breast lump was performed. On histopathological examination, the lesion showed fibrosis with dense lymphocytic infiltration around the lobules. Diabetic fibrous mastopathy was diagnosed. Physicians should be aware of the association of long-standing diabetes mellitus with the development of fibrous mastopathy. CT is considered a useful tool to differentiate diabetic mastopathy from breast cancer.     

Insulin-dependent diabetic mastopathy : A case report

We report a case of insulin-dependent diabetic fibrous mastopathy, which clinically simulated breast cancer. The patient is a 55-year-old woman with stony-hard breast lumps, who had been treated with insulin for diabetes mellitus. Mammmography revealed a highly-dense mass shadow in the left breast and ultrasonography detected hypoechoic lesions with acoustic shadows in both breasts, suggestive of malignancy. Excisional biopsy was performed for the left breast lump. On histopathological examination, this was fibrosis with dense lymphocytic infiltration around lobules, which is a characteristic feature of diabetic fibrous mastopathy.     

Differential impact of non-insulin-dependent diabetes mellitus and insulin-dependent diabetes mellitus on breast reconstruction outcomes

While the comparative safety of breast reconstruction in diabetic patients has been previously studied, we examine the differential effects of insulin and non-insulin-dependence on surgical/medical outcomes. Patients undergoing implant/expander or autologous breast reconstruction were extracted from the National Surgical Quality Improvement Program 2005–2012 database. Preoperative and postoperative variables were analyzed using chi-square and Student’s t test as appropriate. Multivariate regression modeling was used to evaluate whether non-insulin-dependent diabetes mellitus (NIDDM) or insulin-dependent diabetes mellitus (IDDM) is independently associated with adverse 30-day events following breast reconstruction. Of 29,736 patients meeting inclusion criteria, 23,042 (77.5 %) underwent implant/expander reconstructions, of which 815 had NIDDM and 283 had IDDM. Of the 6,694 (22.5 %) patients who underwent autologous reconstructions, 286 had NIDDM and 94 had IDDM. Rates of overall and surgical complications significantly differed among non-diabetic, NIDDM and IDDM patients in both the implant/expander and autologous cohorts on univariate analysis. After multivariate analysis, NIDDM was significantly associated with surgical complications (OR 1.511); IDDM was significantly associated with medical (OR 1.815) and overall complications (OR 1.852); and any type of diabetes was significantly associated with surgical (OR 1.58) and overall (OR 1.361) complications after autologous reconstruction. Diabetes of any type was not associated with any type of complication after implant/expander reconstruction. In this large, multi-institutional study, diabetes mellitus was significantly associated with adverse outcomes after autologous, but not implant-based breast reconstruction. The multivariate analysis in this study adds granularity to the differential effects of NIDDM and IDDM on complication risk.     

Metabolic disorders and breast cancer risk (United States)

Objective: To clarify the hormonal context of breast cancer etiology we used data from a large, population-based case–control study to investigate the relationship between breast cancer risk and a history of diabetes mellitus, disorders associated with estrogen stimulation (uterine fibroids, endometriosis, gallstones), and disorders associated with androgen stimulation (acne, hirsutism, and polycystic ovaries). Methods: Breast cancer patients between 50 and 75 years old were identified from state-wide tumor registries in Wisconsin, Massachusetts, and New Hampshire; controls were randomly selected from drivers' license lists (age less than 65) or Medicare enrollment files (age 65–74). Information on reproductive history, medical history, and personal habits was obtained by telephone interview. A total of 5659 cases and 5928 controls were interviewed and provided suitable data. Results: There was no overall association between breast cancer risk and reported history of diabetes mellitus, endometriosis, uterine fibroids, gallstones, or cholecystectomy. However, the disorders with androgenic associations all conferred an increased risk: the overall odds ratio (OR) for a history of acne was 1.4 (95% CI 1.0–1.9), that for hirsutism was 1.2 (95% CI 0.81–1.8), and that for polycystic ovaries 1.6 (95% CI 0.8–3.2). Diabetes mellitus diagnosed before age 35 conferred an odds ratio of 0.52 (95% 0.25–1.1), while diabetes diagnosed at a later age was associated with an increased risk (OR = 1.2, 95% CI 1.0–1.4). Conclusions: Androgen-related phenomena are likely to be important in the etiology of breast cancer.     

Autoantibodies against insulin and β-islet cells in pancreatic adenocarcinoma: A possible explanation for diabetes mellitus

To evaluate the prevalence of autoantibodies against the b-islet cells (ICA) and the molecule of insulin (IAA) in the serum of patients with pancreatic adenocarcinoma (PA), we examined the sera of 36 newly diagnosed pancreatic adenocarcinoma patients for the presence of these antibodies, using an enzyme-linked immuno-assay method. These results were correlated with survival. Ten patients with insulin-dependent diabetes mellitus (IDDM) and 21 healthy volunteers were evaluated as age-matched controls. Twenty out of 36 (57%) PA patients were found to have detectable ICA autoantibodies and 17 (48%) PA patients had detectable IAA antibodies. Five out of 10 (50%) and 3 out of 10 (30%) IDDM patients had ICA and IAA antibodies, respectively. None of the healthy volunteers was positive for either of the autoantibodies examined. The difference was statistically very significant and the presence of high serum titers of both autoantibodies was associated with a worse outcome for these patients than for those without such autoantibodies. Our data suggest that the high incidence of diabetes mellitus in patients with PA may be attributed to the presence of these antibodies. Further clinical studies are needed to establish the above antibodies as prognostic markers of pancreatic cancer. © 1996 Wiley-Liss, Inc.     

A case of diabetic mastopathy with multiple lesions mimicking breast cancer

We report a case of diabetic mastopathy with multiple unilateral lesions in an insulin dependent patient. The patient was a 62-year-old woman with two hard tumors in the right breast, who had been treated with insulin for diabetes mellitus. Mammography revealed a highly dense tumor in the right breast, while ultrasonography showed two irregular hypoechoic lesions with marked posterior acoustical shadowing, suggesting scirrhous carcinoma. On magnetic resonance imaging the two lesions had slightly heterogeneous enhancement. Aspiration breast cytology showed insufficient cellular material for evaluation. Excisional biopsy was performed because the patient wanted confirmation and treatment. Fibrosis with dense lymphocytic infiltration around the lobules and ducts was diagnosed histopathologically. These findings were compatible with diabetic fibrous mastopathy. Although this disease is thought to be a diabetes-induced reaction of autoimmune origin, multiple lesions are rare. This is the first case of unilateral multiple lesions of diabetic mastopathy.     

Clinical observations of pancreatic diabetes caused by pancreatic carcinoma, and survival period

Background. Pancreatic carcinoma is often associated with diabetes mellitus. The interrelationship between them is very interesting and important for clinical examination and treatment. Methods. We examined diabetes mellitus in our patients with pancreatic carcinoma, especially those with invasive ductal pancreatic carcinoma, who were admitted to the National Kyushu Cancer Center between 1972 and 1998, in relation to secondary (pancreatic) diabetes, obstructive pancreatitis, angiopathies, treatment, and prognosis. Results. Diabetes mellitus was found at a high frequency (53.1%) in patients with invasive ductal pancreatic carcinoma and was mostly thought to be secondary diabetes (45.9%), caused, in part, by obstructive pancreatitis following pancreatic tumor recognized on the first admission. Control of blood glucose with insulin was sometimes difficult, but was indispensable for the treatment of pancreatic carcinoma. Diabetic angiopathies are usually not seen in patients with pancreatic diabetes caused by pancreatic carcinoma, because the survival period of patients with pancreatic carcinoma has been limited. Furthermore, in spite of the absence of angiopathies, the survival period was significantly lower in pancreatic carcinoma patients with diabetes than in those without diabetes. Conclusion. Diabetes in patients with invasive ductal pancreatic carcinoma is usually secondary diabetes, occurring in part as a consequence of obstructive pancreatitis shown at the beginning of the clinical course. The duration of diabetes is too short for marked diabetic angiopathies to develop, and the survival period in patients with invasive ductal pancreatic carcinoma with diabetes is also short compared with that of those patients without diabetes. Received: March 13, 2000 / Accepted: November 9, 2000     

Characteristics of the clinical course of breast cancer in patients with diabetes mellitus

Clinical course of breast cancer was studied in 119 patients suffering concomitant diabetes mellitus. Peculiarities of clinical course of breast cancer versus type of diabetes mellitus were analysed. Rapid growth and dissemination of tumor were observed in cases of insulin-dependent diabetes, whereas in patients with insulin-non-dependent disease long-term postoperative remissions were registered.     

Diabetes mellitus and the risk of primary liver cancer

The relationship between diabetes mellitus and primary liver cancer was investigated in a case-control study conducted in Italy between 1984 and 1996 on 428 cases with incident, histologically confirmed hepatocellular carcinoma, 59 with gallbladder and bile duct cancer, and 1,502 control subjects in the hospital for acute non-neoplastic diseases. Sixty-four cases of hepatocellular carcinoma vs. 87 controls reported a history of diabetes, corresponding to an odds ratio (OR) of 2.3 after allowance for age, sex and area of residence, and of 2.1 [95% confidence interval (CI) = 1.4–3.2] after further allowance for alcohol and tobacco consumption, history of hepatitis and liver cirrhosis, body mass index and history of liver cancer in first-degree relatives. The ORs were similar both for subjects diagnosed with diabetes below age 45, who most likely had insulin-dependent diabetes, and for those diagnosed later, who were likelier to have non-insulin-dependent diabetes. The OR was 2.3 for subjects whose diabetes was diagnosed <5 years before diagnosis of liver cancer, 1.9 for those diagnosed 5–9 years in advance and 2.2 for those diagnosed since 10 years or more. Five cases of gallbladder and bile duct cancer reported a history of diabetes: the corresponding OR was 1.2 (95% CI 0.5–2.9). The OR of hepatocellular carcinoma was 2.4 for males and 2.0 for females, 3.0 for subjects diagnosed with liver cancer under age 60 and 1.8 for those diagnosed at age 60 or over. None of the other covariates considered, including education, history of hepatitis, liver cirrhosis and alcohol drinking showed any meaningful modifying effect or interaction. The potential pathogenic mechanisms include liver alteration—and consequent cell proliferation—in subjects with diabetes. Thus a history of diabetes mellitus could explain about 8% (95% CI 5–11) of cases of liver cancer in this population. Int. J. Cancer 73:204–207, 1997. © 1997 Wiley-Liss, Inc.     

Peripheral blood mononuclear cell dihydropyrimidine dehydrogenase activity in volunteers with and without diabetes mellitus

 It has been reported that cancer patients with diabetes mellitus receiving a continuous infusion of 5-fluorouracil (5-FU) have more toxicity and higher plasma 5-FU levels than patients without diabetes mellitus. Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in the catabolism of 5-FU. DPD activity in peripheral blood mononuclear cells has been reported to correlate inversely with 5-FU plasma levels in patients. We therefore undertook a study to compare the activity of DPD in peripheral blood mononuclear cells of human subjects with and without diabetes mellitus. The study groups comprised 43 volunteers with and 39 without diabetes mellitus, and peripheral blood mononuclear cell DPD activity was assayed on samples obtained between 8 a.m. and 11 a.m. DPD activity was not decreased in diabetic subjects. There was no relationship between DPD activity and gender, body mass index, or race. There was a modest correlation between DPD activity and age (r=0.19, P=0.08). We conclude that increases in 5-FU-related toxicities in diabetics must be related to factors other than peripheral blood mononuclear cell DPD activity. Received: 24 March 1995/Accepted: 21 July 1995     

Relationship between diabetes and risk of second primary contralateral breast cancer

Breast cancer survivors have a substantially higher risk of developing a second primary contralateral breast cancer (CBC) compared to the risk of breast cancer among women in the general population. While data regarding the relationship between diabetes and breast cancer incidence are inconsistent, diabetes is more clearly linked to an elevated risk of all-cause mortality among breast cancer survivors. However, no prior studies have assessed its impact on CBC risk. We assessed the relationship between diabetes, and CBC risk in a population-based nested case–control study consisting of women 40–79 years of age diagnosed with a first primary ER-positive invasive breast cancer. It included 322 women who developed a second primary CBC and 616-matched control women diagnosed only with a first breast cancer. We used conditional logistic regression to quantify associations between diabetes and CBC risk. Compared to women without a history of diabetes, diabetics had a 2.2-fold [95% confidence interval (CI) 1.3–3.6] increased risk of CBC. This risk was more pronounced among women diagnosed with their first breast cancer before age 60 years (odds ratio, OR = 11.5, 95% CI 2.4–54.5), compared to those diagnosed at age 60 years or older (OR = 1.5, 95% CI 0.8–2.7, P for interaction = 0.011). Diabetics diagnosed with breast cancer appear to have an elevated risk of CBC. This is the first study to report this relationship, but if confirmed efforts to insure that diabetic breast cancer survivors are carefully screened for second breast cancers may be warranted.     

Increased prevalence of prior breast cancer in women with newly diagnosed diabetes

SummaryObjective There is growing evidence of a link between type 2 diabetes and breast cancer, possibly through insulin resistance and/or hyperinsulinemia. Because insulin levels are at their highest prior to the development of diabetes, breast cancer risk may be even greater during the pre-diabetes period.Research design and methods In this cross-sectional study, women aged 55–79 years living in Ontario, Canada, with newly diagnosed diabetes from 1994 to 2002 were identified from a validated, population-based database (N = 82,390). Prior history of breast cancer in this group was recorded from 1964 until their diabetes diagnosis from a linkable cancer registry, and was compared to a similarly aged comparison group without diabetes (N = 411,950).Results Prior breast cancers were identified in 3.7% of women with diabetes and in 3.1% women without diabetes (odds ratio, OR 1.22, 95% confidence interval, CI 1.17–1.27, p < 0.0001). The mean time from breast cancer diagnosis to diabetes diagnosis was 7.9 years. The likelihood of a breast cancer history remained significantly higher in women with diabetes after adjustment for age, income and physician visits (OR 1.13, 95% CI 1.09–1.18, p < 0.0001).Conclusions These results suggest that breast cancer risk may be increased in the pre-diabetes phase and may have implications for screening and prevention strategies. Further studies are required to better characterize the processes that link insulin resistance, diabetes and breast cancer.     

Effect of diabetes mellitus on the epidemiology and outcomes of colon cancer

Objectives To assess the effect of diabetes mellitus (DM) on the pathogenesis and outcomes from colon cancer. Methods A retrospective chart review was conducted on 1853 patients with colon cancer. Results A higher percentage of males than females with colon cancer had DM (16.2% vs 11.3%; p<0.01). Males had a slightly lower risk of dying from colon cancer (RR−0.88; p=0.08). There was no difference in the median age of diagnosis of colon cancer in patients with and without DM, but a larger proportion of patients with diabetes mellitus were ≥70 yr at diagnosis (50% vs 43%) (p=0.0004). No significant relationship was noted between stage of colon cancer or survival and presence of DM. Conclusions DM did not affect either the stage at diagnosis, or outcomes from colon cancer. More males with colon cancer tended to have DM and a larger proportion of patients with DM were ≥70 yr at the time of diagnosis.     

A case of lymphocytic mastopathy requiring differential diagnosis from primary breast lymphoma

Lymphocytic mastopathy is a benign breast disease characterized by dense fibrosis, lobular atrophy, and aggregates of lymphocytes in a periductal and perivascular distribution. The condition affects young to middle-aged women and frequently shows an association with diabetes mellitus or autoimmune disorders. Here, we report a case of the disease clinically and radiologically mimicking primary breast neoplasms. The patient was a 50-year-old woman without diabetes who presented with two firm lumps in her right breast. Breast imaging findings from mammography, ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI), respectively, revealed an abnormal appearance suspicious of malignancy. A core-needle biopsy specimen showed atypical accumulation of lymphoid cells, which was not easy to differentiate from primary breast lymphomas. Moreover, ¹⁸fluorodeoxyglucose positron emission tomography (FDG-PET) examination detected abnormal uptake in the same lesions. Histological examination of a surgically obtained specimen showed characteristic appearance of lymphocytic mastopathy, which predominantly consisted of B-lymphocytes. In our case, it was difficult to distinguish this entity from breast cancer or low-grade B-cell lymphoma without surgical biopsy.     

乳腺癌合并2型糖尿病患者沉默信息调节因子1表达及其意义

 【摘要】　目的　研究沉默信息调节因子1（SIRT1）在乳腺癌合并2型糖尿病中的表达,分析其与乳腺癌合并2型糖尿病患者相关临床病理指标之间的关系。方法　应用免疫组织化学方法检测30例乳腺癌合并2型糖尿病患者、65例非糖尿病乳腺癌患者的乳腺癌组织和18例正常乳腺组织中SIRT1的表达情况。结果　SIRT1在非糖尿病、合并2型糖尿病乳腺癌组织和正常乳腺组织中的表达率分别为76.9 %（50／65）、50.0 %（15／30）、5.6 %（1／18）,乳腺癌组织均高于正常乳腺组织（χ2＝24.618,P＝0.000）,合并2型糖尿病者SIRT1的表达率低于非糖尿病患者（χ2＝6.886,P＝0.009）。合并2型糖尿病的乳腺癌患者SIRT1的表达与淋巴结转移（P＝0.011）、pTNM分期（P＝0.028）、p53蛋白的表达（P＝0.003）以及Her-2的表达（P＝0.031）均呈正相关。结论　SIRT1在乳腺癌合并2型糖尿病患者乳腺癌组织中过表达,但阳性表达率低于未合并糖尿病乳腺癌组,其可能是影响糖尿病病程进展的重要分子; SIRT1的表达与多项临床病理指标有关,可能成为判断合并2型糖尿病乳腺癌恶性程度及评估预后的生物学指标。     

Body size in different periods of life, diabetes mellitus, hypertension, and risk of postmenopausal endometrial cancer (Sweden)

Objective: To measure the association between endometrial cancer risk and obesity at age 18 and recently, adult weight gain, diabetes mellitus and hypertension. Methods: We performed a population-based, nationwide case–control study among postmenopausal women aged 50–74 years in Sweden, including 709 incident cases with histopathologically verified endometrial cancer and 3368 controls. Results: Compared to lean women (recent body mass index (BMI), i.e. kg/m² below 22.5), overweight women (recent BMI 28–29.99) had a 50% increase in risk for endometrial cancer (OR 1.5, 95% CI 1.0–2.1). Obese women (recent BMI 30–33.99) had a 3-fold increased risk (OR 2.9, 95% CI 2.0–4.0), and markedly obese women (recent BMI 34) a 6-fold increased risk (OR 6.3, 95% CI 4.2–9.5). The OR for Type 2 diabetes mellitus was 1.5 (95% CI 1.0–2.1) and for Type 1 diabetes mellitus it was 13.3 (3.1–56.4). The effect of recent BMI was similar for tumors having different degrees of differentiation and myometrial invasion, and did not vary with age, time since menopause, smoking status, diabetes mellitus, and use of contraceptives. Hypertension increased risk only among obese women. BMI at age 18, height, and adult weight change were not independent risk factors. Conclusions: Recent overweight/obesity and diabetes mellitus (Types 1 and 2) are associated with endometrial cancer risk. Hypertension increases risk among obese women.     

Diabetes mellitus and breast cancer: a retrospective population-based cohort study

SummaryPurpose Evidence suggests that women with type 2 diabetes may be at increased risk of breast cancer, possibly due to chronic exposure to insulin resistance and/or hyperinsulinemia. The purpose of this study was to compare the incidence of breast cancer in postmenopausal women with and without diabetes.Methods Using population-based validated health databases from Ontario, Canada, this retrospective cohort study compared breast cancer incidence between women, aged 55–79 years, with newly diagnosed diabetes (n=73,796) to women without diabetes (n=391,714).Results Women with diabetes were slightly older, were more likely to reside in a lower income neighborhood, had greater comorbidity, and had more annual physician visits than women without diabetes. After 2.2 million person-years of follow-up from 1994 to 2002, breast cancer incidence was 2.97/1000 person-years in the diabetes group and 2.75/1000 person-years in the non-diabetes group. After adjustment for age and income, there was a significant increase in breast cancer among women with diabetes (hazard ratio, HR, 1.08, 95% confidence interval, CI, 1.01–1.16, p=0.021).Conclusion This study found a small but significant increase in incident breast cancer in a predominantly postmenopausal population of women with diabetes, when compared to women without diabetes. These results support the possibility that insulin resistance or some other aspect of type 2 diabetes may promote breast cancer, and may further direct treatment and prevention strategies.     

Impact of diabetes mellitus on treatment outcomes in patients with nasopharyngeal cancer

Background and purpose To determine the influence of diabetes mellitus on stages and long-term outcomes among patients with nasopharyngeal cancer. Material and methods The study summarized 37 patients who were diagnosed as having diabetes mellitus and nasopharyngeal cancer and treated by radiotherapy between January 1999 and December 1999. With a median follow-up of 34.6 mo, we analyzed differences in RFS, MFS, DFS, and OS between the diabetes and the non-diabetes group. Results 37 patients were involved in our study. According to the Chinese Fuzhou staging system for NPC, which was modified in 1992, 2 patients belong to stage I, 9 stage II, 17 stage III, and 6 stage IV. The 4-yr RFS of diabetes group and non-diabetes group was 52.1% vs 68.2%, the 4-yr MFS was 73.0% vs 72.0%, the 4-yr DFS was 35.1% vs 65.1%, and the OS was 67.6% vs 75.7%. The Wilcoxon (Gehan) test showed there was no significant difference between the two groups of RFS, MFS, and OS, while the diabetes group had a worse DFS than non-diabetes group (Wilcoxon p=0.0047). Conclusions Patients with diabetes had a worse DFS than non-diabetes, but statistic tests did not show significant differences in RFS, MFS, and OS; further studies should be continue to find out the results in the future.