Prostate Cancer Risk Stratification by Simple Scoring of the Current pT3 Lesions: A Proposal for a New Pathologic T-Staging System.

Cancer spread beyond the prostate, including extraprostatic extension (other than seminal vesicle or bladder invasion; EPE)/microscopic bladder neck invasion and seminal vesicle invasion (SVI) currently classified as pT3a and pT3b lesions, respectively, does not uniformly indicate poor oncologic outcomes. Accurate risk stratification of current pT3 disease is therefore required. We herein further determined the prognostic impact of these histopathologic lesions routinely assessed and reported by pathologists, particularly their combinations. We assessed consecutive 2892 patients undergoing radical prostatectomy for current pT2 (n = 1692), pT3a (n = 956), or pT3b (n = 244) disease at our institution between 2009 and 2018. Based on our preliminary findings, point(s) were given (1 point to focal EPE, microscopic bladder neck invasion, or unilateral SVI; 2 points to nonfocal/established EPE or bilateral SVI) and summed up in each case. Our cohort had 0 point (n = 1692, 58.5%; P0), 1 point (n = 243, 8.4%; P1), 2 points (n = 657, 22.7%; P2), 3 points (n = 192, 6.6%; P3), 4 points (n = 76, 2.6%; P4), and 5 points (n = 32, 1.1%; P5). Univariate analysis revealed associations of higher points with significantly worse biochemical progression-free survival, particularly when P4 and P5 were combined. In multivariable analysis (P0 as a reference), P1 (hazard ratio [HR], 1.57; P = .033), P2 (HR, 3.25; P < .001), P3 (HR, 4.01; P < .001), and P4 + P5 (HR, 5.99; P < .001) showed significance for the risk of postoperative progression. Meanwhile, Harrell C-indexes for the current pT staging, newly developed point system, and the Cancer of the Prostate Risk Assessment post-Surgical (CAPRA-S) score were 0.727 (95% CI, 0.706-0.748), 0.751 (95% CI, 0.729-0.773), and 0.774 (95% CI, 0.755-0.794), respectively, for predicting progression. We believe our data provide a logical rationale for a novel pathologic T-staging system based on the summed points, pT1a (0 point), pT1b (1 point), pT2 (2 points), pT3a (3 points), and pT3b (4 or 5 points), which more accurately stratifies the prognosis of prostate cancer.

Clinicopathologic Predictors of Clinical Outcomes in Mammary Adenoid Cystic Carcinoma: A Multi-institutional Study.

Adenoid cystic carcinoma (AdCC) is an uncommon type of invasive breast carcinoma with a favorable prognosis. However, some cases are aggressive. The study aims to define the clinicopathologic predictors of outcome. Clinical, radiological, and pathologic variables were recorded for 76 AdCC cases from 11 institutions. The following histologic characteristics were evaluated by the breast pathologist in each respective institution, including Nottingham grade (NG), percentages of various growth patterns (solid, cribriform, trabecular-tubular), percentage of basaloid component, tumor borders (pushing, infiltrative), perineural invasion, lymphovascular invasion, necrosis, and distance from the closest margin. Various grading systems were evaluated, including NG, salivary gland-type grading systems, and a new proposed grading system. The new grading system incorporated the growth pattern (percent solid, percent cribriform), percent basaloid morphology, and mitotic count using the Youden index criterion. All variables were correlated with recurrence-free survival. Nineteen (25%) women developed local and/or distant recurrence. Basaloid morphology (≥25% of the tumor) was identified in 20 (26.3%) cases and a solid growth pattern (using ≥60% cutoff) in 22 (28.9%) cases. In the univariate analysis, the following variables were significantly correlated with worse recurrence-free survival: solid growth pattern, basaloid morphology, lymphovascular invasion, necrosis, perineural invasion, and pN-stage. In the multivariate analysis including basaloid morphology, pN-stage, lymphovascular invasion, and perineural invasion, basaloid morphology was statistically significant, with a hazard ratio of 3.872 (95% CI, 1.077; 13.924; P =.038). The NG and the new grading system both correlated with recurrence-free survival. However, grade 2 had a similar risk as grade 3 in the NG system and a similar risk as grade 1 in the new grading system. For solid growth patterns and basaloid morphology, using a 2-tier system with 1 cutoff was better than a 3-tier system with 2 cutoffs. Basaloid morphology and solid growth pattern have prognostic values for AdCC, with a 2-tier grading system performing better than a 3-tier system.

The Clinical Significance of pT3a Lesions as Well as Unilateral Versus Bilateral Invasion Into the Seminal Vesicle in Men With pT3b Prostate Cancer: A Proposal for a New pT3b Subclassification.

CONTEXT.­: Seminal vesicle invasion (SVI) as pT3b prostate cancer generally, but not uniformly, indicates poor prognosis. OBJECTIVE.­: To determine the clinical impact of pT3a lesions (ie, extraprostatic extension other than seminal vesicle or bladder invasion [EPE], microscopic bladder neck invasion [mBNI]), as well as unilateral (Uni) versus bilateral (Bil) SVI in pT3b disease. DESIGN.­: We assessed radical prostatectomy findings and long-term oncologic outcomes in 248 consecutive patients with pT3b disease. RESULTS.­: Focal EPE, nonfocal EPE, mBNI, Uni-SVI, and Bil-SVI were identified in 13 (5.2%), 206 (83.1%), 48 (19.4%), 109 (44.0%), and 139 (56.0%) cases, respectively. Of possible combinations, we eventually divided our cases into 3 cohorts-Group 1: Uni/Bil-SVI and EPE-/mBNI- (n = 28; 11.3%); Group 2: Uni-SVI and EPE or mBNI (n = 103; 41.5%); and Group 3: Bil-SVI and EPE or mBNI (n = 70; 28.2%) or Uni/Bil-SVI and EPE+/mBNI+ (n = 47; 19.0%). Group 3 patients showed significant adverse histopathologic findings, compared with Group 1 or Group 2 patients. Kaplan-Meier analysis revealed that the prognosis was worse in the following order: Group 1, Group 2, and Group 3; and the differences in progression-free survival between any 2 groups were statistically significant. These significant differences were also seen in subgroups, such as those without or with adjuvant therapy before recurrence and those without lymph node metastasis. Additionally, Group 3 patients had a significantly higher risk of cancer-specific mortality than Group 2 patients. In multivariate analysis (Group 2 as a reference), Group 1 (hazard ratio [HR] = 0.169, P = .01) and Group 3 (HR = 1.620, P = .04) showed significance for progression. CONCLUSIONS.­: From these significant findings, we propose a novel pT3b subclassification, namely pT3b1 (Group 1), pT3b2 (Group 2), and pT3b3 (Group 3), which more accurately stratifies its prognosis.

Metastatic melanoma posing as a pelvic mass.

Pelvic metastasis of melanoma is extremely rare and may pose a diagnostic challenge. We present a case report of a female with a history of colon cancer who underwent exploratory surgery for a pelvic mass that was suspicious for ovarian malignancy. Pathology was consistent with both recurrent colon cancer as well as synchronous newly diagnosed metastatic melanoma.

Clinical Significance of Perineural Invasion by Prostate Cancer Detected on Needle Core Biopsy.

OBJECTIVES: The clinical impact of the laterality of perineural invasion (PNI) by prostate cancer remains poorly understood. We herein compared radical prostatectomy (RP) findings and long-term oncologic outcomes in patients with prostate cancer with PNI in two prostate biopsy (PBx) sites. METHODS: We retrospectively assessed 170 consecutive patients undergoing systematic sextant PBx where PNI had been detected in two of six PBx sites, followed by RP. RESULTS: PNI occurred unilaterally in 140 (82.4%) cases and bilaterally in 30 (17.6%) cases. Compared with unilateral PNI, bilateral PNI was significantly associated with a higher number of cancer-positive sites and longer total tumor length on PBx. However, there were no significant differences in RP findings, including tumor grade/stage and tumor volume, between unilateral and bilateral PNI cohorts. Kaplan-Meier analysis revealed that patients with bilateral PNI had a significantly higher risk of disease progression after RP than those with unilateral PNI (P = .038). In multivariate analysis, bilateral PNI (vs unilateral PNI) showed significance for progression (hazard ratio, 2.281; P = .023). CONCLUSIONS: In PBx specimens exhibiting PNI in two sextant sites, bilateral PNI was found to be associated with poorer prognosis as an independent predictor but not worse histopathologic features in RP specimens compared with unilateral PNI.

The Clinical Significance of Either Extraprostatic Extension or Microscopic Bladder Neck Invasion Alone Versus Both in Men With pT3a Prostate Cancer Undergoing Radical Prostatectomy: A Proposal for a New pT3a Subclassification.

The prognosis of prostate cancers exhibiting extraprostatic extension [other than bladder or seminal vesicle invasion (EPE)] and/or microscopic bladder neck invasion (mBNI) is variable, and further risk stratification is required. We herein assessed radical prostatectomy findings and long-term oncologic outcomes in consecutive 957 patients with pT3a disease. The patient cohort was divided into 4 groups, focal EPE (F-EPE) only (n=177; 18.5%), nonfocal/established (E-EPE) only (n=634; 66.2%), mBNI only (n=51; 5.3%). The rate of positive surgical margin and estimated volume of tumor were significantly higher in patients with both EPE and mBNI than in those with either. In addition, compared with F-EPE or mBNI only, E-EPE only was significantly associated with higher Grade Group, lymph node metastasis, and larger tumor volume. Kaplan-Meier analysis revealed a comparable prognosis after prostatectomy between those showing F-EPE only versus mBNI only ( P =0.986), and these 2 cohorts were combined for further analysis. Then, patients showing E-EPE only had a significantly higher or lower risk of progression compared with those showing F-EPE or mBNI only ( P <0.001) or both EPE and mBNI ( P <0.001), respectively. These significant differences in progression-free survival were also seen in subgroups, including those with or without undergoing adjuvant therapy before recurrence and those showing no lymph node metastasis. In multivariate analysis, F-EPE or mBNI only (hazard ratio=0.524, P =0.003) or both EPE and mBNI (hazard ratio=1.465, P =0.039) (vs. E-EPE only) showed significance for progression. Based on these findings, we propose a novel pT3a subclassification, pT3a1 (F-EPE or mBNI alone), pT3a2 (E-EPE alone), and pT3a3 (both EPE and mBNI).

Gastrointestinal Tract Injury by Yttrium-90 Appears Largely Restricted to Resin Microspheres But Can Occur Years After Embolization.

Radioembolization therapy utilizes yttrium-90 (Y90) impregnated resin (SIR-Spheres) or glass (TheraSpheres) microspheres to selectively target hepatic lesions via transarterial radioembolization. Occasional cases of gastrointestinal tract injury, secondary to nontargeted delivery of microspheres, have been reported, but large descriptive pathology series are lacking. We identified 20 cases of histologically confirmed mucosal injury associated with Y90 from 17 patients and assessed the corresponding clinical and pathologic sequelae. The mucosal biopsies were obtained from 1 to 88 months following Y90 therapy (median: 5 mo). Most cases were gastric (17, 85%), while the remaining were duodenal. Endoscopic ulceration was seen in the majority of cases (16, 80%), and mucosal erythema in the remaining 4. Histologically, a majority (19, 95%) of cases showed rounded, dark blue to purple microspheres measuring 4 to 30 µm, consistent with resin microspheres. A single case with glass microspheres demonstrated 26 µm translucent beads. Histologic evidence of ulceration was appreciated in 14 (70%) cases, and the microspheres were clearly intravascular in 6 (30%). A foreign body giant cell reaction to the microspheres was uncommon (3 cases, 15%). We additionally performed a retrospective review of all gastrointestinal tissue obtained postprocedure from 784 sequential patients treated with Y90 microspheres. Three patients (0.4%) demonstrated the presence of resin microspheres upon histologic examination. No cases involving glass-based Y90 were identified ( P =0.0078), despite the majority of patients having received glass radioembolization (630, 80%). This increased risk of secondary sphere dissemination is likely related to the increased number of particles required per activity for resin versus glass microspheres. We conclude that Y90 microspheres may be encountered in the gastrointestinal tract years after initial liver-targeted therapy and, when present, are often associated with mucosal ulceration. This finding is less likely to be encountered in patients who received Y90 radioembolization utilizing glass microspheres.

The Clinical Significance of Perineural Invasion by Prostate Cancer on Needle Core Biopsy: Involvement of Single Versus Multiple Sextant Sites.

CONTEXT.­: Perineural invasion (PNI) by prostate cancer has been associated with adverse pathology, including extraprostatic extension. However, the significance of PNI quantification on prostate biopsy (PBx) remains unclear. OBJECTIVE.­: To compare radical prostatectomy (RP) findings and long-term outcomes in patients whose PBx had exhibited PNI. DESIGN.­: We assessed 497 consecutive patients undergoing sextant (6-site/≥12-core) PBx showing conventional adenocarcinoma followed by RP. RESULTS.­: PNI was found in 1 (n = 290)/2 (n = 132)/3 (n = 47)/4 (n = 19)/5 (n = 5)/6 (n = 4) of the sites/regions of PBx. Compared with a single PNI site, multiple PNIs were significantly associated with higher preoperative prostate-specific antigen, higher Grade Group (GG) on PBx or RP, higher pT or pN category, positive surgical margin, and larger estimated tumor volume. When compared in subgroups of patients based on PBx GG, significant differences in RP GG (GG1-3), pT (GG1-2/GG1-3/GG2/GG3), surgical margin status (GG1-3/GG3/GG5), or tumor volume (GG1-2/GG1-3/GG2/GG3) between 1 versus multiple PNIs were observed. Moreover, there were significant differences in prostate-specific antigen (PNI sites: 1-2 versus 3-6/1-3 versus 4-6/1-4 versus 5-6), RP GG (1-3 versus 4-6/1-4 versus 5-6), pT (1-2 versus 3-6/1-3 versus 4-6), pN (1-3 versus 4-6), or tumor volume (1-2 versus 3-6/1-4 versus 5-6). Outcome analysis revealed significantly higher risks of disease progression in the entire cohort or PBx GG1-2/GG1-3/GG2/GG3/GG5 cases showing 2 to 6 PNIs, compared with respective controls with 1-site PNI. In multivariate analysis, multisite PNI was an independent predictor for progression (hazard ratio = 1.556, P = .03). CONCLUSIONS.­: Multiple sites of PNI on PBx were associated with worse histopathologic features in RP specimens and poorer prognosis. PNI may thus need to be specified, if present, in every sextant site on PBx, especially those showing GG1-3 cancer.

The Clinical Impact of pT3a Lesions in Patients With pT3b Prostate Cancer Undergoing Radical Prostatectomy.

CONTEXT.­: Seminal vesicle invasion (SVI) by prostate cancer (pT3b disease) has been considered as a key prognostic factor. OBJECTIVE.­: To assess the clinical impact of T3a lesions (ie, extraprostatic extension other than bladder neck invasion [BNI] or SVI [EPE], microscopic bladder neck invasion [mBNI]) in pT3b disease. DESIGN.­: We compared radical prostatectomy findings and long-term oncologic outcomes in 248 patients with pT3b disease, with versus without EPE/mBNI. RESULTS.­: Extraprostatic extension/mBNI was found in 219 (88.3%)/48 (19.4%) cases, respectively. Extraprostatic extension was significantly associated with higher preoperative prostate-specific antigen (PSA) level, higher rates of positive surgical margin (pSM) and lymphovascular invasion (LVI), and larger tumor volume. Similarly, mBNI was significantly associated with higher PSA level, higher rates of Grade Group(s) 4-5 or 5, pSM, LVI, and pN1, and larger tumor volume. Significant differences in all of these clinicopathologic features (except lymph node metastasis) between EPE-/mBNI+ or EPE+/mBNI- and EPE+/mBNI+ cases were also observed. Outcome analysis revealed that patients with EPE (P < .001) or mBNI (P < .001) had a significantly higher risk of disease progression than respective controls. Notably, there were significant differences in progression-free survival between EPE-/mBNI+ or EPE+/mBNI- cases and EPE-/mBNI- (P = .001) or EPE+/mBNI+ (P < .001) cases. In multivariate analysis, EPE (hazard ratio [HR] = 6.53, P = .009) and mBNI (HR = 2.33, P = .003), as well as EPE-/mBNI+ or EPE+/mBNI- (HR = 11.7, P = .01) and EPE+/mBNI+ (HR = 25.9, P = .002) versus EPE-/mBNI-, showed significance for progression. CONCLUSIONS.­: From these significant findings, we propose a novel pT3b subclassification: pT3b1 (SVI alone without EPE or mBNI), pT3b2 (SVI with either EPE or mBNI), and pT3b3 (SVI with both EPE and mBNI).

The Clinical Impact of Unilateral Versus Bilateral Invasion Into the Seminal Vesicle in Patients With Prostate Cancer Undergoing Radical Prostatectomy.

CONTEXT.­: Seminal vesicle involvement by prostate cancer has generally been considered as a key prognosticator. OBJECTIVE.­: To assess the clinical significance of unilateral (Uni) versus bilateral (Bil) seminal vesicle invasion (SVI). DESIGN.­: We compared radical prostatectomy findings and long-term oncologic outcomes in 248 patients showing Uni-SVI (n = 139) versus Bil-SVI (n = 109). RESULTS.­: Tumor grade was significantly higher in Bil-SVI cases than in Uni-SVI cases. Additionally, Bil-SVI was significantly associated with a higher incidence of lymphovascular invasion, lymph node metastasis, or positive surgical margin, and larger estimated tumor volume. When the histopathologic features at SVI foci were compared, Grade Group (GG) 3-5/4-5/5 and cribriform morphology were significantly more often seen in Bil-SVI. Outcome analysis revealed that patients with Bil-SVI had a significantly higher risk of disease progression (P < .001) than patients with Uni-SVI. Significantly worse progression-free survival in patients with Bil-SVI was also observed in all subgroups examined, including those with no immediate adjuvant therapy (IAT) (n = 139; P = .01), IAT (n = 109; P = .001), pN0 disease (n = 153; P = .002), or pN1 disease (n = 93; P = .006). In multivariate analysis, Bil-SVI (versus Uni-SVI) showed significance for progression in the entire (hazard ratio [HR] = 1.83, P = .01), IAT (HR = 2.90, P = .006), and pN0 (HR = 2.05, P = .01) cohorts. Meanwhile, tumor grade at SVI (eg, GG4, GG5), as an independent predictor, was significantly associated with patient outcomes. CONCLUSIONS.­: Bil-SVI was found to be strongly associated with worse histopathologic features on radical prostatectomy and poorer prognosis. Pathologists may thus need to report Uni-SVI versus Bil-SVI, along with other histopathologic findings, such as Gleason score, at SVI in prostatectomy specimens.

Progressive Nodular Histiocytosis: Report of a Case and Review of the Literature.

Progressive nodular histiocytosis (PNH) is a rare condition characterized by progressive eruption of multiple yellowish-brown papules and nodules on the skin and mucous membranes. We present the case of a 37-year-old Caucasian man with gradually increased appearance of nodular lesions on the forehead and right temple. These lesions were initially diagnosed as xanthomas and did not respond to intralesional injections of triamcinolone. Additional biopsy revealed an intense dermal infiltrate of foamy mononuclear epithelioid cells with a minor admixture of plasma cells, lymphocytes, and scattered multinucleated giant cells. On immunohistochemical staining, the lesional cells were positive for CD163 and CD68 and negative for CD1a, thus confirming a mononuclear-macrophage lineage. The clinical presentation and the histological impression lead to the diagnosis of PNH. This condition could be challenging, mimicking microscopically similar lesions of the non-Langerhans cell histiocytosis group. Although uncommon, PNH stands out due to its clinical and microscopic features and should be taken into consideration in the differential diagnosis of cutaneous histiocytoses.

An Unusual Case of Acute Appendicitis due to Metastatic Prostatic Adenocarcinoma.

Acute appendicitis is a common surgical emergency in older adults. In the elderly, like in younger cohorts, acute appendicitis most commonly arises without neoplastic underpinnings. However, the occurrence of acute appendicitis in a patient with a concurrent abdominopelvic malignancy should trigger suspicion for the possibility of a metastatic appendiceal neoplasm. We present the case of a 66-year-old man with a background of a biochemically recurrent prostatic adenocarcinoma who presented to the emergency department with acute appendicitis. Histopathologic examination of the resected appendix revealed an unexpected metastatic spread from his prostatic adenocarcinoma.

A 235 Kb deletion at 17q21.33 encompassing the COL1A1, and two additional secondary copy number variants in an infant with type I osteogenesis imperfecta: A rare case report.

BACKGROUND: Osteogenesis imperfecta (OI) is a rare group of disorders characterized by increased susceptibility to fractures due to genetically determined bone fragility. About 90% of cases are due to mutations in COL1A1 (17q21.33) or COL1A2 (7q21.3) resulting in quantitative or qualitative defects in type I collagen, a key structural constituent of bone. OI due to complete COL1A1 deletion is rare. METHODS: We present a case of OI type I in a Caucasian female referred at 10 months of age for investigation of multiple fractures associated with minimal or no known trauma, small stature, and blue sclera. Her father has four to five lifetime fractures, blue sclera, normal stature, and a 14.5 kilobase (kb) deletion of COL1A1 detected by targeted array performed at an outside institution. Microarray comparative genomic hybridization was performed on the proband and all members of the family. RESULTS: A previously unreported 235 kb deletion at 17q21.33 encompassing COL1A1, ITGA3, PDK2, SGCA, and HILS1 was detected in the proband. Also identified in both the proband and sibling is a maternally inherited 283 kb gain at 8p21.3 encompassing CSGALNACT1 and a 163 kb loss at 10q21.3 encompassing CTNNA3. Analysis in the father revealed the same size deletion at 17q21.33 as in the proband. CONCLUSION: Together with previously reported cases of COL1A1 deletions, this case report emphasizes the importance of a whole-genome DNA copy number assessment in patients suspected for OI, which will elucidate the presence of precise COL1A1 deletions and any pathogenic secondary copy number variations.

A rare histologic subtype of hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma: report of a case.

Worldwide, primary liver cancer is the fourth leading cause of cancer mortality. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Sarcomatoid hepatocellular carcinoma (SHC) is a rare subtype of HCC with conventional HCC admixed with areas with sarcomatoid morphology. SHC is an aggressive, rapidly growing tumor with unfavorable prognosis. Pedunculated SHC is an uncommon presentation of SHC. Due to its rarity, much remains unknown about the etiopathogenesis, molecular underpinnings, and treatment of SHC. We present a case of an exophytic SHC arising in a background of cirrhosis in an older adult. A resection was performed, but the patient subsequently developed multiple additional intrahepatic metastatic lesions necessitating further treatment with chemotherapy.

Sonographic Evaluation of Genitourinary Inflammatory Pseudotumors and Its Mimics.

ABSTRACT: Inflammatory pseudotumor is a relatively rare, nonneoplastic lesion composed of inflammatory cells and myofibroblastic spindle cells that can be identified on sonographic evaluation of the genitourinary system. These lesions are thought to be an inflammatory response to insults such as surgery, trauma, infection, or malignancy. Such lesions need to be distinguished from true neoplasms and other benign lesions, including inflammatory responses and infectious processes. Identification of inflammatory pseudotumors and its mimics is important for radiologists to guide patient treatment and follow-up. This pictorial essay presents sonographic features of inflammatory pseudotumors of the genitourinary tract and its mimics with cross-sectional imaging and histopathology, where available.

Should Ki67 immunohistochemistry be performed on all lesions in multifocal small intestinal neuroendocrine tumours?

AIMS: Well-differentiated small intestinal neuroendocrine tumours (SI-NETs) are often multifocal, and this has been suggested to impart worse disease-free survival. Practice guidelines have not been established for World Health Organisation (WHO) grading of multiple primary lesions. METHODS AND RESULTS: We identified 68 patients with ileal/jejunal SI-NET for a combined total of 207 primary lesions. Each case was evaluated for patient age and sex; size of all tumours; presence of lymph node metastases, mesenteric tumour deposits or distant metastases; and disease-specific outcome. Ki67 staining was performed on all 207 primary lesions. The relationship between multifocality and clinicopathological factors was compared using Fisher's exact test. Outcome was tested using Cox proportional hazard regression. Forty-two patients had unifocal disease, and 26 had multifocal disease (median five lesions, range = 2-32). Most tumours were WHO grade 1 (201 of 207, 97%). Of the five patients with grades 2/3 tumours, three patients had unifocal disease, one patient had two subcentimetre grade 2 lesions (including the largest) and eight subcentimetre grade 1 lesions, and one patient had one 1.6-cm grade 3 lesion and one subcentimetre grade 1 lesion. There was a positive correlation between tumour size and Ki67 index (coefficient 0.28; 95% confidence interval 0.05-0.52, P = 0.017). There was no significant association between multifocality and nodal metastases, mesenteric tumour deposits, distant metastases or disease-specific survival. CONCLUSIONS: In patients with multifocal SI-NET, unless a particular lesion has a high mitotic rate, only staining the largest lesion for Ki67 should serve to grade almost all cases accurately. Multifocality does not appear to significantly impact patient survival.