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INTRODUCTION/OBJECTIVE Antineutrophil cytoplasmic antibodies (ANCA) serology can aid in the diagnosis and classification of ANCA-associated vasculitides (AAV). However, it is often ordered in patients without clinical manifestations of vasculitis. In this retrospective chart review, we aim to better understand the clinical practices on ANCA testing. METHODS We retrospectively reviewed patients' charts for the indications and diagnostic outcomes of ANCA tests. All ANCA tests ordered at two Canadian hospitals (a community hospital and an academic tertiary hospital) between January and December 2016 were included in the study. Descriptive statistics are used. RESULTS A total of 302 ANCA tests were included. The majority (n = 198, 65.6%) were ordered without an indication for testing. For those patients with at least 1 clinical manifestation of AAV (n = 104), 25% were ANCA positive and 18.3% resulted in a diagnosis of AAV. In comparison, among those without a clinical manifestation of AAV (n = 198), only 1.5% were ANCA positive and none was diagnosed with AAV. All patients diagnosed with AAV had at least 1 indication for ANCA testing. The three most common clinical presentations in patients with a final diagnosis of AAV were glomerulonephritis (81.8%), pulmonary hemorrhage (45.5%), and multiple lung nodules (31.8%). CONCLUSION To our knowledge, this is the first study that evaluates patients with both positive and negative ANCA test results in an inpatient setting. We demonstrated a low rate of ANCA positivity and AAV diagnosis in patients without clinical manifestations of AAV. Overall, there is a high rate of ANCA testing without an indication at our academic institution. This over-testing may be curbed by strategies such as a gating policy, culture changes, and clinician education. Key Points • AAV is a clinical-pathological diagnosis, and despite the usefulness of ANCA testing, it does not confirm nor rule out AAV. • ANCA testing for the diagnosis of AAV is generally only indicated when there is a clear manifestation of AAV. • Although patients with AAV may occasionally present without classic signs and symptoms, the diagnostic utility of ANCA serology in this setting is low, and testing is more likely to result in a false-positive or false-negative test. • If clinical suspicion remains high despite negative ANCA testing, clinicians should seek consultation with a rheumatologist.

A 43-yr old female with two prior renal transplants for renal failure associated with diabetes, retinopathy and coronary artery disease developed diarrhea. Her medications included mycophenolate mofetil, an immunosuppressive medication documented to cause sprue-like mucosal changes in the small intestine. Later studies revealed a small intestinal mucosal lesion characterized by marked crypt hyperplasia, villous atrophy and increased intra-epithelial lymphocytes. Serological studies for celiac disease were negative and repeated biopsies despite a strict gluten-free diet, revealed histopathological persistence of a severely abnormal sprue-like enteropathy. Eventually, further biopsies of her small intestine revealed superimposed changes characterized by dense sub-epithelial collagen deposits histochemically staining positive for trichrome, typical of collagenous sprue and representing an expansion of published pathological features of mycophenolate-associated small intestinal mucosal disease.

Background The aim of this study is to describe and quantitatively analyze the histopathology of proximal long head biceps (LHB) tendinopathy in patients who have undergone LHB tenodesis. The hypothesis is that severe histopathologic changes of the LHB tendon (LHBT) will most likely be reflected with improved postoperative clinical outcomes. Methods The study included patients with isolated LHB tendinopathy or LHB tendinopathy associated with concomitant shoulder pathologies. All had failed conservative treatment (12 months) and had a positive pain response (> 50% reduction) pre-operatively after LHB tendon injection with local anesthetic. All underwent biceps tenodesis procedure between 2008 and 2014. Tendon specimens were collected and histologically analyzed with the semi-quantitative Bonar scoring system. Minimum follow-up time was 1 year. A subset of patients was retrospectively reviewed postoperatively and evaluated employing visual analogue score (VAS), short form survey (SF-12), American Shoulder and Elbow Surgeon (ASES) score, Disability of Arm, Shoulder and Hand (DASH) score, and Oxford Shoulder Score (OSS) and postoperative return to work status. Results Forty-five biceps tendon specimens were obtained from 44 patients (mean age 50 ± 9.6 years). Histopathological analyses demonstrated advanced degenerative changes with myxoid degeneration and marked collagen disorganization. Minimal inflammation was identified. There were no regional differences in histopathological changes. Clinical outcomes did not correlate significantly with severity of histopathologic changes. Conclusions This study confirms that LHBT specimens in patients undergoing tenodesis demonstrate with the use of the Bonar score histopathologic changes of chronic degeneration and not inflammation. The correct histopathologic terminology for this process is LHB tendinosis. The histopathological changes appear uniform throughout the entire length of the LHBT which may inform the nature of the procedure performed.

Antineutrophil cytoplasmic antibodies (ANCA) serology can aid in the diagnosis and classification of ANCA-associated vasculitides (AAV). However, it is often ordered in patients without clinical manifestations of vasculitis. In this retrospective chart review, we aim to better understand the clinical practices on ANCA testing.We retrospectively reviewed patients' charts for the indications and diagnostic outcomes of ANCA tests. All ANCA tests ordered at two Canadian hospitals (a community hospital and an academic tertiary hospital) between January and December 2016 were included in the study. Descriptive statistics are used.A total of 302 ANCA tests were included. The majority (n = 198, 65.6%) were ordered without an indication for testing. For those patients with at least 1 clinical manifestation of AAV (n = 104), 25% were ANCA positive and 18.3% resulted in a diagnosis of AAV. In comparison, among those without a clinical manifestation of AAV (n = 198), only 1.5% were ANCA positive and none was diagnosed with AAV. All patients diagnosed with AAV had at least 1 indication for ANCA testing. The three most common clinical presentations in patients with a final diagnosis of AAV were glomerulonephritis (81.8%), pulmonary hemorrhage (45.5%), and multiple lung nodules (31.8%).To our knowledge, this is the first study that evaluates patients with both positive and negative ANCA test results in an inpatient setting. We demonstrated a low rate of ANCA positivity and AAV diagnosis in patients without clinical manifestations of AAV. Overall, there is a high rate of ANCA testing without an indication at our academic institution. This over-testing may be curbed by strategies such as a gating policy, culture changes, and clinician education. Key Points • AAV is a clinical-pathological diagnosis, and despite the usefulness of ANCA testing, it does not confirm nor rule out AAV. • ANCA testing for the diagnosis of AAV is generally only indicated when there is a clear manifestation of AAV. • Although patients with AAV may occasionally present without classic signs and symptoms, the diagnostic utility of ANCA serology in this setting is low, and testing is more likely to result in a false-positive or false-negative test. • If clinical suspicion remains high despite negative ANCA testing, clinicians should seek consultation with a rheumatologist.

The objective of the study was to determine the clinical features and treatment course in Canadian patients with dermatomyositis (DM) associated with the anti-melanoma differentiation-associated gene 5 antibody (MDA5). A retrospective chart review of consecutive patients with anti-MDA5 antibody DM from two Canadian tertiary care centre between 2014 and 2018 was done. Twenty-one consecutive cases of anti-MDA5-positive DM were identified. Median age at diagnosis was 52 years, 71% Asians, predominantly Chinese, and 29% Caucasians. In this case series, all patients had either typical DM rash, or vasculopathy and ulceration unique to anti-MDA5-positive DM. 38% of the patients had rapid progressive (RP)-interstitial lung disease (RP-ILD), 33% had chronic ILD and 29% had asymptomatic ILD. Anti-Ro52 positivity was more prevalent in RP-ILD. Mortality was high in the RP-ILD group, with five deaths in eight patients. Lung transplant was life-saving intervention for three of the RP-ILD patients who survived. A review of the literature in treating RP-ILD associated with anti-MDA5 is presented. Although evidence is limited to small case series, cyclophosphamide (CYC) for refractory skin lesions, and CYC or mycophenolate mofetil plus a calcineurin inhibitor or rituximab (RTX) for RP-ILD appear efficacious. This is the largest North American case series of anti-MDA5-positive DM patients to date. There is a wide spectrum of clinical presentation of this entity. Survival is poor in those with RP-ILD; early aggressive immunosuppression and timely lung transplant were life-saving in our patients with RP-ILD.

Cancer survivors treated with abdominal or pelvic radiation therapy (RT) for childhood cancer have an increased risk of colorectal cancer. However, clinical guidelines are inconsistent on recommendations regarding the early initiation of screening in these patients due to the lack of supporting evidence that these patients pass through a pre-invasive phase, in which adenomatous polyps can be detected and removed. To determine the prevalence of adenomatous polyps in cancer survivors treated with RT for childhood cancer; the prevalence in average-risk patients aged 17–49; and the prevalence in average-risk patients aged 50–75. We conducted a retrospective study comparing the prevalence of adenomatous polyps among three patient groups: childhood cancer survivors aged 17–49 with prior RT who underwent colonoscopy screening from 2006 to 2017; age- and gender-matched patients in the average-risk population; and average-risk patients aged 50–75. One hundred and forty-five patients were included in the study. The proportion of patients with adenomatous polyps in the cancer survivor group was significantly higher than that in the age- and gender-matched average-risk group (58.6 vs 17.2%, p = 0.00) and higher than the average-risk group aged 50–75 (58.6 vs 27.6%, p = 0.009). The prevalence of adenomas with high-risk features was higher in the survivor group compared to patients aged 50–75 (20.7 vs 3.5%, p = 0.015). Cancer survivors treated with RT for childhood cancer have a higher prevalence of adenomatous polyps compared to the average-risk population. These findings support the early initiation of colonoscopy screening 10 years after radiation therapy, even in patients who have received RT doses below 30 Gy.

There is increasing evidence for a role of early life gut microbiota in later development of asthma in children. In our recent study, children with reduced abundance of the bacterial genera Lachnospira, Veillonella, Faecalibacterium, and Rothia had an increased risk of development of asthma and addition of these bacteria in a humanized mouse model reduced airway inflammation. In this Addendum, we provide additional data on the use of a humanized gut microbiota mouse model to study the development of asthma in children, highlighting the differences in immune development between germ-free mice colonized with human microbes compared to those colonized with mouse gut microbiota. We also demonstrate that there is no association between the composition of the gut microbiota in older children and the diagnosis of asthma, further suggesting the importance of the gut microbiota-immune system axis in the first three months of life.

Collagenous colitis is an inflammatory mucosal disorder of the colon with distinctive histopathological features, including a thickened subepithelial collagen layer. The clinical course is usually benign, but serious complications, including death, may occur. In the present report, a 69-year-old woman with watery diarrhea and collagenous colitis developed bloody diarrhea that was refractory to treatment medications, including corticosteroids and azathioprine. Endoscopic and histopathological studies showed a focal neutrophilic inflammatory process that progressed to a diffuse and extensive form of colitis, eventually requiring total proctocolectomy. Careful histological review of the resected colon showed no evidence of persistent collagenous colitis. These findings suggest an important need for continued long-term follow-up of patients with collagenous colitis because superimposed and serious colonic complications may occur, including a severe and extensive pancolitis refractory to medications and necessitating total proctocolectomy.

Zinc has been shown to be accumulated in N-methyl-N-nitrosourea (MNU)-induced rat mammary tumors. Zinc is required for cell proliferation and tumorigenesis is characterized by dysregulation of cell proliferation. An accumulation of zinc in mammary tumors perhaps indicates a reliance on zinc to sustain tumor growth. Limiting zinc supply by means such as reduced zinc intake should negatively modulate mammary tumorigenesis. Our objective was to determine the effects of zinc status on MNU-induced mammary tumorigenesis in sexually mature female rats. Twenty-one-day-old Sprague-Dawley rats were assigned to low-zinc (3 mg zinc/kg diet) or adequate-zinc (12 mg zinc/kg diet) ad libitum or pair-fed control group (n = 25-33 rats/ group). On day 50 of age, all rats were intraperitoneally injected with MNU (50 mg/kg body wt) to induce mammary tumorigenesis. Rats were further maintained on their assigned diet until 14 weeks post-MNU injection. Total food intake and overall body weight gain were lower in low-zinc rats than in adequate-zinc ad libitum control rats, but were similar to adequate-zinc pair-fed control rats. Plasma zinc concentration was lower in low-zinc rats than in adequate-zinc ad libitum and pair-fed control rats, confirming moderately low-zinc status in low-zinc rats. Tumor incidence (46 versus 84 and 80%; P < 0.05) and tumor multiplicity (0.8 versus 5.0 and 2.6 tumors/rat; P < 0.05) and tumor number (28 versus 123 and 66 tumors) were reduced in low-zinc rats compared with that in adequate-zinc ad libitum and pair-fed control rats, respectively. Tumor latency in low-zinc and adequate-zinc pair-fed control rats was not significantly different, but was longer than in adequate-zinc ad libitum control rats (P < 0.05), suggesting that reduced food intake associated with low-zinc intake prolonged tumor latency. Tumor burden and size were not affected by zinc intake. Overall, our observations showed that moderately low-zinc status suppressed MNU-induced rat mammary tumorigenesis.

A previously well, 24-year-old male resident of Vancouver, British Columbia, presented to the emergency department with a two-month history of gradual onset of painless jaundice, dark urine and pale stool. At the time of presentation, he experienced a dramatic rise in the levels of the following liver enzymes: alkaline aminotransferase 272 U/L; alanine aminotransferase 244 U/L; gamma-glutamyl transferase 487 U/L; and alkaline phosphatase 1085 U/L, with an international normalized ratio of 1.0 and an albumin level of 39 g/L. His serum bilirubin level was highly elevated (367 μmol/L) with a conjugated fraction of 282 μmol/L. Hepatitis was the presumptive diagnosis based on positive serology for hepatitis A. However, a computed tomography scan of the abdomen revealed a complex, cystic mass 10.9 cm × 17.9 cm in size in the epigastric region with rim calcifications (Figure 1). This was concerning for a malignant or infective process and the patient was referred to the hepatobiliary surgery service. Figure 1) Coronal contrast-enhanced computed tomography image demonstrating a large complex mass arising from the liver with a central cystic component and an irregular, thick enhancing wall containing punctate calcifications The patient experienced no fever, cough, nausea, vomiting or abdominal pain. He had no known contacts with similar symptoms. He had travelled to Belgium, but had not travelled to the tropics or Northern Canada. There was no known exposure to animals, including canines. He underwent an endoscopic retrograde cholangiopancreatography with placement of bilateral biliary stents and ultrasound-guided percutaneous drainage of the hepatic abscess. The subsequent culture of the abscess fluid grew Candida albicans, which was treated with fluconazole. The patient became febrile and his jaundice did not improve and, thus, a right hepatectomy and cholecystectomy was performed. The surgical specimen contained a complex hydatid cyst 12 cm in diameter (Figure 2). There were numerous hyalinized profiles in the cyst wall consistent with daughter cysts (Figure 3). The final histological diagnosis was echinococcus with features suggestive of Echinococcus multilocularis. The patient was treated postoperatively with albendazole, 400mg/day orally. Subsequent serology was positive for serum immunoglobulin G antibodies to echinococcus confirmed by immunoblot. He remains asymptomatic without evidence of recurrence and his liver enzyme levels have normalized. Figure 2) A Lining of echinococcal cyst demonstrating the thick laminated layer produced by the parasite with adjacent degenerated and inflamed tissue (hematoxylin and eosin stain, original magnification ×100). B Internal aspect of a cyst with parasite ... Figure 3) Multiple collapsed small cysts in the hepatic parenchyma. A The wall is composed of carbohydrates as demonstrated by periodic acid-Schiff positivity (original magnification ×100). B The presence of multiple small cysts produces an infiltrating ...

Background Although optic nerve gliomas (ONGs) are generally slow-growing with a good prognosis, factors for identifying cases that may pursue a more aggressive course are not well established. The authors investigated cell proliferation markers for prognostic significance in a series of resected ONGs. Methods Twelve cases of resected ONG were identified out of a total of 38 examined at the authors9 institution between 1981 and 2008. Clinical data were reviewed. Ki-67 and p53 immunohistochemical staining was performed on the tumour mass and the proximal resection margin. Results All of the tumours were low-grade pilocytic astrocytomas. Six patients were suspected to have histologically positive proximal resection margins. Ki-67 labelling indices (LI) ranged from 0.3% to 5.9% (mean 2.4%) for the tumour mass and from 0 to 2.1% (mean 0.9%) for the proximal resection margins. One patient had evidence of progression 25 months after subtotal surgical resection. The Ki-67 LI of the proximal resection margin in this case was similar to the main tumour value. The other six patients with histologically negative proximal resection margins all had lower relative proliferation indices at the resection margin when compared with the tumour mass and are currently stable with no evidence of progression. Conclusions Routine histological examination of resection margins may be difficult to interpret in the setting of reactive gliosis. A resection margin with a Ki-67 LI similar to the tumour bulk value may have an adjunctive role in identifying cases with the potential for growth thereby facilitating the decision-making process for future management and surveillance.

Intestinal lymphangiectasia in the adult may be characterized as a disorder with dilated intestinal lacteals causing loss of lymph into the lumen of the small intestine and resultant hypoproteinemia, hypogammaglobulinemia, hypoalbuminemia and reduced number of circulating lymphocytes or lymphopenia. Most often, intestinal lymphangiectasia has been recorded in children, often in neonates, usually with other congenital abnormalities but initial definition in adults including the elderly has become increasingly more common. Shared clinical features with the pediatric population such as bilateral lower limb edema, sometimes with lymphedema, pleural effusion and chylous ascites may occur but these reflect the severe end of the clinical spectrum. In some, diarrhea occurs with steatorrhea along with increased fecal loss of protein, reflected in increased fecal alpha-1-antitrypsin levels, while others may present with iron deficiency anemia, sometimes associated with occult small intestinal bleeding. Most lymphangiectasia in adults detected in recent years, however, appears to have few or no clinical features of malabsorption. Diagnosis remains dependent on endoscopic changes confirmed by small bowel biopsy showing histological evidence of intestinal lymphangiectasia. In some, video capsule endoscopy and enteroscopy have revealed more extensive changes along the length of the small intestine. A critical diagnostic element in adults with lymphangiectasia is the exclusion of entities (e.g. malignancies including lymphoma) that might lead to obstruction of the lymphatic system and "secondary" changes in the small bowel biopsy. In addition, occult infectious (e.g. Whipple's disease from Tropheryma whipplei) or inflammatory disorders (e.g. Crohn's disease) may also present with profound changes in intestinal permeability and protein-losing enteropathy that also require exclusion. Conversely, rare B-cell type lymphomas have also been described even decades following initial diagnosis of intestinal lymphangiectasia. Treatment has been historically defined to include a low fat diet with medium-chain triglyceride supplementation that leads to portal venous rather than lacteal uptake. A number of other pharmacological measures have been reported or proposed but these are largely anecdotal. Finally, rare reports of localized surgical resection of involved areas of small intestine have been described but follow-up in these cases is often limited.

Granulomatous mastitis is an inflammatory breast condition of unknown etiology. Management remains controversial and treatment algorithms are lacking from the literature. Few resources exist that discuss breast reconstruction following extirpation. This descriptive case series reviews the clinicopathologic features of granulomatous mastitis.We describe the surgical management undertaken at our institution including General and Plastic Surgery procedures. Eleven clinical charts and histologic slides of biopsy specimens were reviewed in our health region between 1992 and 2007. Demographic data, clinical presentation, and radiologic findings were tabulated. Treatment consisted of empirical antibiotics and surgical excision. Procedures performed included incision and drainage (n = 8), excisional biopsy (n = 15), partial mastectomy (n = 5), partial mastectomy with reduction mammaplasty (n = 2), and mastectomy with TRAM flap reconstruction (n = 1).Treatment was successful in all but one case. Multiple surgeries for recurrent lesions were often required to achieve final remission. Following extirpation, we recommend delayed breast reconstruction to monitor for recurrence.

Lipopolysaccharide (LPS) triggers a global activation of Inflammatory responses leading to liver injury in humans. Zinc pretreatment has been shown to prevent LPS-induced hepatic necrosis. In North America, suboptimal zinc status is more common than once realized. However, the effect of inadequate zinc nutrition on the host's susceptibility to LPS-induced liver injury is not known. The objective of this study was to determine whether marginal zinc deficiency would render rats more susceptible to LPS-induced liver injury. Weanling Sprague-Dawley rats were assigned to one of three dietary treatment groups: marginally low zinc ad libitum (Z3; 3 mg zinc/kg diet), adequate zinc ad libitum (Z30; 30 mg zinc/kg diet), or adequate zinc pair-fed (Z30P) group. After 6 weeks, each dietary treatment group was further divided into LPS-control (saline) groups (C-Z3, C-Z30P, C-Z30) and LPS-treatment (1 mg/kg body weight, intraperitoneal, 8 hrs) groups (LPS-Z3, LPS-Z30P, LPS-Z30). LPS reduced the serum zinc concentration and increased the liver zinc concentration regardless of dietary zinc intake. Serum alanine aminotransferase level was higher in the LPS-Z3 rats than in the LPS-Z30P and LPS-Z30 rats. LPS also induced hepatocyte necrosis and neutrophil infiltration into the liver sinusoids. This LPS-induced liver damage was more severe in the LPS-Z3 rats than in the LPS-Z30P and LPS-Z30 rats. Together these findings have demonstrated that marginal zinc deficiency increased the susceptibility to LPS-induced liver injury in rats. These results indicate that patients with sepsis who have suboptimal zinc nutrition status may be at higher risk of developing greater liver damage.

Departments of Medicine (Gastroenterology) and Pathology, University of British Columbia, Vancouver, British Columbia Correspondence: Dr Hugh James Freeman, University of British Columbia Hospital, 2211 Wesbrook Mall, Vancouver, British Columbia V6T 1W5. Telephone 604-822-7216, fax 604-822-7236, e-mail hugfree@shaw.ca Received for publication April 4, 2010. Accepted April 14, 2010 Case presentation and images A 78-year-old woman experienced intermittent watery diarrhea for more than one year. There was no previous antibiotic use, travel or other medical history. The physical examination was normal. Laboratory studies, including bloodwork and fecal cultures, were negative. Colonoscopy revealed sigmoid diverticulosis and a broad-based sessile, ‘carpet-like’ polypoid lesion at the hepatic flexure appearing to occupy approximately 40% to 50% of the colonic circumference; consequently, the lesion was biopsied only (Figure 1) and ink-tattooed (for later laparoscopic removal). Biopsy sections (Figures 2 and 3) showed collagenous colitis with thickening of the basal collagen plate, an irregular lower border, entrapped nuclei, loss of overlying surface epithelium and increased inflammatory cells in the lamina propria. Subepithelial multinucleated giant cells were present (arrows). A trichrome stain highlighted the thickened basal collagen plate with entrapped nuclei (Figure 4). Over the next few weeks, her diarrhea completely resolved on a high-fibre diet regimen alone.

Twenty-one cases of vulvar Paget's disease were studied to assess possible prognostic indicators, including presence and depth of invasion, status of resection margins, tumor DNA cell content, and immunoreactivity for p53 and estrogen receptor proteins. Immunostaining for cytokeratin 7 (CK7), cytokeratin 20 (CK20), and gross cystic disease fluid protein-15 (GCDFP) were also performed. Patients were 45 to 82 years of age (mean, 66.9 years). Ten of 21 patients (47.6%) had invasive Paget's disease. Dermal invasion wasor = 1 mm in 7 of 10 cases and 2 mm, 3 mm, and 8 mm in the remaining three invasive tumors. Of the seven patients with minimally invasive Paget's disease (or = 1 mm depth of invasion), five are alive with no evidence of disease, one died of an unrelated illness, and one is alive with biopsy-proven in situ Paget's disease, having refused operative treatment. Of the three patients with more than minimally invasive Paget's disease (1 mm), all had nodal metastases; one patient is alive with no evidence of disease, one died of undertermined causes, and one died of metastatic Paget's disease. The remaining 11 patients had Paget's disease confined to the epidermis and its adnexal structures. Seven of these patients were alive at last follow-up with no evidence of disease. Of the remaining four patients, one died of metastatic cervical cancer, one died of metastatic bladder cancer, one died of an unrelated illness, and one patient is alive with biopsy-proven in situ Paget's disease and awaiting operative treatment. Twenty of the 21 cases represented primary vulvar Paget's disease while one represented possible local spread from a cervical adenocarcinoma. The immunoprofiles were GCDFP+/CK7+/CK20- in 14 cases, GCDFP+/CK7+/CK20+ in 4 cases, and GCDFP-/CK7+/CK20- in 2 cases. All tumors were estrogen receptor-negative. Immunostaining for p53 was positive in 16 tumors and negative in four tumors. Seven of 12 (58%) patients with positive margins experienced local recurrence of Paget's disease, while the disease recurred in 1 of 4 patients with negative margins. Recurrence was observed in 3 of 5 patients with diploid tumors and in 4 of 10 patients with aneuploid tumors. Neither of these differences is statistically significant. This study supports the recognition of a category of minimally invasive vulvar Paget's disease that has a low risk of distant metastasis and death caused by disease. Status of surgical resection margins, tumor cell DNA ploidy, estrogen receptor expression, and p53 immunoreactivity are not predictive of local recurrence.