High-risk Histopathologic Features Research Articles

Clinical and histopathological correlation: A study on 334 eyes with retinoblastoma from Vietnam

Purpose: To elucidate the clinical features which predict high-risk histopathological factors for subsequent metastatic disease as well as to report the incidence of these high-risk histopathological factors in a cohort of Asian patients with retinoblastoma.
 Design: A retrospective and non-randomized sequential cases series.
 Methods: A retrospective study was done on 334 eyes with retinoblastoma at Vietnam National Institute of Ophthalmology during a 10 year period (January 2004 – December 2013). All pathology specimens and medical records were reviewed and assessed for invasion and clinical signs.
 Results: Among 334 eyes, 225 (67.4%) had high-risk retinoblastoma and 109 (22.6%) had non-high-risk features on histopathology. The high-risk histopathological features included anterior chamber seeding (48.2%), iris infiltration (14.7%), ciliary body involvement (14.1%), massive choroidal invasion (29.9 %), post-laminar optic nerve invasion (21.2%), invasion of optic nerve transection (9.6 %), combined choroidal and optic nerve invasion (9.6 %), scleral invasion (3.3%), and extra-scleral infiltration (11.4%). The significant clinical features in high-risk group versus non-high-risk group included hyphema (19.6% vs 3.7%, p < 0.001), pseudohypopyon (19.1% vs 6.4%, p = 0.001), iris neovascularization (25.3% vs 5.5%, p < 0.001), vitreous seeding (72.4% vs 37.6%, p < 0.001), staphyloma (24% vs 4.6%, p < 0.001) and scleritis (20% vs 3.7%, p < 0.001).
 Conclusions: Clinical signs including hyphema, pseudohypopyon, iris neovascularization, vitreous seeding, staphyloma, and scleritis were significantly associated with high-risk features on histopathology. Globe preserving methods should be used with caution in patients with these signs.

Diffuse Infiltrating Retinoblastoma - Atypical Presentation of Retinoblastoma in late childhood

Retinoblastoma (RB) is the most common intraocular malignancy in children that is usually diagnosed before the age of 5 years. An atypical presentation of RB in late childhood and absence of calcification on imaging studies poses a diagnostic challenge for the ophthalmologist.1 Herein we report the clinical features and management of a similar case with atypical presentation. A 10 year old boy presented with a history of leucocoria in the right eye for two months. There was no other relevant ocular, medical and family history. On ophthalmic examination, visual acuity was presence of light perception with inaccurate projection of rays in all the four quadrants in the right eye and 6/6 in left eye. The left eye was unremarkable on examination. On slit lamp biomicroscopy, the right eye showed exudates in the anterior chamber that were touching the corneal endothelium and invading the iris (Figure 1). Examination of the posterior segment on B scan ultrasonography demonstrated retinal detachment with haemorrhages, without any evidence of a distinct retinal mass or calcification, in the right eye. However, in view of a clinical suspicion of retinoblastoma, CT scan of the orbits was performed which revealed a few specks of calcification in the superotemporal quadrant close to the ora serrata, with findings of retinal detachment and sub-retinal exudation in the right eye (Figure 2). Further imaging with Contrast MRI of the orbits and the brain revealed the presence of a sub-retinal exudates, that showed post contrast enhancement on T1 weighted images. In addition, a small mass noted on T2 weighted images (Figure 3). The general physical examination and systemic examination were within normal limits. On the basis of clinical examination and imaging studies, a working diagnosis of Diffuse Infiltrating Retinoblastoma (DIRB) was made. Enucleation was carried out and a primary implant was inserted.The postoperative period was uneventful. Histopathological examination of the enucleated eye confirmed the presence of a poorly differentiated retinoblastoma and showed diffuse involvement of the ocular coats (Figures 4 & 5). In view of high risk histopathological features, child was advised to receive post-operative adjuvant systemic chemotherapy. An artificial eye was prescribed at six weeks follow-up. At one year follow-up, the patient was doing well, with no local recurrence or systemic metastasis.

Knowledge, attitudes and decision-making preferences of men considering participation in the TROG RAVES Prostate Cancer Trial (TROG 08.03)

Background and purposeThe RAVES (Trans-Tasman Radiation Oncology Group 08.03) randomised controlled trial (RCT), compares adjuvant radiotherapy with early salvage radiotherapy in men with high risk histopathological features at prostatectomy. The RAVES Decision Aid study evaluates the utility of a decision aid for men considering participation in the RAVES RCT. We report the RAVES Decision Aid study participants’ attitudes and knowledge regarding RCTs, decision-making preferences and decisional-conflict. Materials and methodsBaseline questionnaires assessed knowledge and attitudes towards RCTs and RAVES RCT. Sociodemographic and clinical predictors of knowledge were examined. Involvement in decision-making and difficulties with the decision-making process were assessed using validated tools. Results127 men (median age=63years) were recruited through urologists (n=91) and radiation oncologists (n=36). Men preferred collaborative (35%) or semi-active (35%) decision-making roles. Most (>75%) felt the RAVES RCT was worthwhile and important with participation being wise. However, nearly half had high decisional-conflict regarding participation. Scores of objective knowledge regarding RCTs and RAVES RCT were low. ConclusionsMost men with high-risk histopathological features at prostatectomy desire active involvement in decision-making regarding further management. Despite positive attitudes towards RCTs and the RAVES RCT, there were gaps in knowledge and high decisional-conflict surrounding participation.

Serous and mucinous borderline ovarian tumours: differences in clinical presentation, high-risk histopathological features, and lethal recurrence rates.

Mucinous and serous borderline ovarian tumours (mBOTs and sBOTs) are controversial diseases. With this systematic review we aim to evaluate the different high-risk histopathological features and recurrence rates. The PubMed database was searched using two terms: {serous AND [(borderline) OR (low malignant potential)] AND ovarian AND tumour} and {mucinous AND [(borderline) OR (low malignant potential)] AND ovarian AND tumour}. Cohorts of either sBOT or mBOT, peer-reviewed, retrospective, or prospective. Lethal recurrence data for micropapillary patterns (MPs), microinvasion, non-invasive and invasive implants, and intraepithelial carcinoma (IECA). The primary measure of effect was the odds ratio of lethal recurrence reduction. Data from patients in 42 studies including 4414 sBOTs and 12 studies including 894 mBOTs were pooled. Of these, 53.3% presented early-stage typical sBOTs, 24.4% presented with MPs, 22.3% presented with microinvasion, 34.4% presented with non-invasive implants, and 7.3% presented with invasive implants. The pooled lethal recurrence rates were, respectively: 18.3, 16.8, 10.7, 16.2, and 33.8%. Patients with MPs were more likely to suffer lethal recurrence when compared with high-stage sBOTs (odds ratio, OR 0.501; P = 0.003), whereas the trend in microinvasive sBOTs did not reach statistical significance. Regarding mBOTs, 61.6% presented with early-stage typical mBOTs, 19.6% presented with microinvasion, 34.8% presented with IECA, and six patients presented with non-invasive implants; none presented with invasive implants. The lethal recurrence rates were, respectively: 3.6, 0, 3.7, and 0%. Micropapillary patterns (MPs) showed a higher risk for lethal recurrence when compared with high-stage sBOTs. Regarding mBOTs, IECA and microinvasion do not play a role in the lethal recurrence rate. Micropapillary pattern confirmed as high-risk in BOT. IECA and microinvasion don't play a role in mucinous BOT.

Comparison of high-risk histopathological features in eyes with primary or secondary enucleation for retinoblastoma

AimsTo compare high-risk histopathology of eyes with primary versus secondary enucleation from patients with retinoblastoma.Patients and methodsA retrospective histopathology review identified 207 eyes enucleated from 202 patients between March 1997...

Magnetic Resonance Imaging-Guided Core Needle Breast Biopsies Resulting in High-Risk Histopathologic Findings: Upstage Frequency and Lesion Characteristics

IntroductionThe purpose of the present study was to determine the malignancy upstage rates and imaging features of high-risk histopathologic findings resulting from magnetic resonance imaging (MRI)-guided core needle breast biopsies. These features include atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), flat epithelial atypia (FEA), and lobular carcinoma in situ (LCIS). Materials and MethodsA retrospective medical record review was performed on all MRI-guided core needle breast biopsies at a single institution from June 1, 2007 to December 1, 2013 to select biopsies yielding high-risk histopathologic findings. The patient demographics, MRI lesion characteristics, and histopathologic features at biopsy and surgical excision were analyzed. ResultsA total of 257 MRI-guided biopsies had been performed, and 50 yielded high-risk histopathologic features (19%). Biopsy site and surgical excision site correlation was confirmed in 29 of 50 cases. Four of 29 lesions (14%) were upstaged: 1 case to invasive ductal carcinoma and 3 cases to ductal carcinoma in situ. ADH alone had an overall upstage rate of 7% (1 of 14), mixed ADH/ALH a rate of 75% (3 of 4), ALH alone or with LCIS a rate of 0% (0 of 7), and FEA a rate of 0% (0 of 4). Only mixed ADH/ALH had a statistically significant upstage rate to malignancy compared with the other high-risk histopathologic subtypes combined. No specific imaging characteristics on MRI were associated with an upstage to malignancy on the statistical analysis. ConclusionMRI-guided breast biopsies yielding high-risk histopathologic features were associated with an overall upstage to malignancy rate of 14% at surgical excision. All upstaged lesions were associated with ADH. FEA and ALH alone or with LCIS were not associated with an upstage to malignancy.

Histopathologic Grading of Anaplasia in Retinoblastoma

To determine whether the degree of tumor anaplasia has prognostic value by evaluating its correlation with high-risk histopathologic features and clinical outcomes in a series of retinoblastoma patients. Retrospective clinicopathologic study. The clinical and pathologic findings in 266 patients who underwent primary enucleation for retinoblastoma were reviewed. The histologic degree of anaplasia was graded as retinocytoma, mild, moderate, or severe as defined by increasing cellular pleomorphism, number of mitoses, nuclear size, and nuclear hyperchromatism. Nuclear morphometric characteristics were measured. The clinical and pathologic data of 125 patients were compared using Kaplan-Meier estimates of survival. Fisher exact test and multivariate regression were used to analyze the association between anaplasia grade and high-risk histologic features. Increasing grade of anaplasia was associated with decreased overall survival (P= .003) and increased risk of metastasis (P= .0007). Histopathologic features that were associated with anaplasia included optic nerve invasion (P < .0001), choroidal invasion (P < .0001), and anterior segment invasion (P= .04). Multivariate analysis considering high-risk histopathology and anaplasia grading as predictors of distant metastasis and death showed that high-risk histopathology was statistically significant as an independent predictor (P= .01 for metastasis, P= .03 for death) but anaplasia was not (P= .63 for metastasis, P= .30 for death). In the absence of high-risk features, however, severe anaplasia identified an additional risk for metastasis (P= .0004) and death (P= .01). Grading of anaplasia may be a useful adjunct to standard histopathologic criteria in identifying retinoblastoma patients who do not have high-risk histologic features but still have an increased risk of metastasis and may need adjuvant therapy.

Prognostic and predictive significance of MSI in stages II/III colon cancer.

In colon cancer, classic disease staging remains the key prognosis and treatment determinant. Although adjuvant chemotherapy has an established role in stage III colon cancer patients, in stage II it is still a subject of controversy due to its restriction to a small subgroup of patients with high-risk histopathologic features. Patients with stage II tumors form a highly heterogeneous group, with five-year relative overall survival rates ranging from 87.5% (IIA) to 58.4% (IIC). Identifying those for whom adjuvant chemotherapy would be appropriate and necessary has been challenging, and prognostic markers which could serve in the selection of patients more likely to recur or benefit from adjuvant chemotherapy are eagerly needed. The stronger candidate in this category seems to be microsatellite instability (MSI). The recently reported European Society for Medical Oncology guidelines suggest that MSI should be evaluated in stage II colorectal cancer patients in order to contribute in treatment decision-making regarding chemotherapy administration. The hypothetical predictive role of MSI regarding its response to 5-fluorouracil-based adjuvant chemotherapy has proven a much more difficult issue to address. Almost every possible relation between MSI and chemotherapy outcome has been described in the adjuvant colon cancer setting in the international literature, and the matter is far from being settled. In this current report we critically evaluate the prognostic and predictive impact of MSI status in patients with stage II and stage III colon cancer patients.

High-Risk Retinoblastoma Based on International Classification of Retinoblastoma: Analysis of 519 Enucleated Eyes

To determine the correlation between the International Classification of Retinoblastoma (ICRB) and histopathologic high-risk retinoblastoma. Retrospective study. A total of 519 patients. Primary enucleation. High-risk retinoblastoma, metastasis, and death. Of 519 primarily enucleated eyes, 87 (17%) were classified as group D and 432 (83%) were classified as group E on the basis of the ICRB. High-risk retinoblastoma was identified in 23% (117/519) of enucleated eyes, including 17% (15/87) group D and 24% (102/432) group E eyes. High-risk histopathologic features of retinoblastoma included anterior chamber involvement (5/15 [33%] group D eyes, 31/102 [30%] group E eyes), isolated massive posterior uveal invasion ≥ 3 mm (7/15 [47%] group D eyes, 22/102 [22%] group E eyes), isolated post-laminar optic nerve invasion (2/15 [13%] group D eyes, 46/102 [45%] group E eyes), and any combination of posterior uveal invasion and optic nerve involvement (7/15 [47%] group D eyes, 37/102 [36%] group E eyes). On logistic regression analysis, massive posterior uveal invasion ≥ 3 mm was more common in group D eyes (P = 0.0442), and post-laminar optic nerve invasion was more common in group E eyes (P = 0.0390). Of 117 patients with high-risk retinoblastoma, systemic adjuvant chemotherapy was administered in 83 patients (71%). Systemic metastasis developed in 0% (0/15) of those with high-risk group D retinoblastoma and 10% (10/102) of those with high-risk group E retinoblastoma over a mean follow-up period of 78 months (median, 62 months; range, 1-419 months). There was no metastasis in any patient (n = 402) classified with non-high-risk retinoblastoma. Of the 10 patients who developed metastasis, 4 had received prior adjuvant chemotherapy and 6 had no prior adjuvant chemotherapy. There was no metastasis in high-risk patients treated with vincristine sulphate, etoposide phosphate, and carboplatin (VEC). Death from metastasis occurred in 4% of high-risk patients (5/117). On the basis of the ICRB, 17% of group D and 24% of group E eyes are at increased risk for metastatic disease. In this study, 8% of patients developed metastasis. There was no metastasis in any patient classified with non-high-risk retinoblastoma. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

The pathology of ocular cancer

Primary cancers of the eye are rare. These include uveal melanoma, a tumor that preferentially affects the choroid of light-eyed, fair-skinned Europeans, and the pediatric retinal neoplasm retinoblastoma, which is slightly more common worldwide. Uveal melanoma kills about half of affected patients. Most succumb to hepatic metastases, which are unresponsive to current therapy. Factors indicative of poor prognosis include tumor size, ciliary body involvement, epithelioid cells, extraocular extension, lymphocytic and melanophagic infiltration, mitotic activity, vascular mimicry patterns, and most importantly, the detection of monosomy 3 and class 2 gene expression profile in tumor cells using special tests. Most retinoblastomas are caused by sporadic somatic mutations in the RB1 gene, but about one-third arise in infants with germline mutations. The latter tend to develop earlier, are often bilateral and are transmissible to offspring as an autosomal dominant trait. Retinoblastoma displays varying degrees of differentiation including Homer Wright and Flexner-Wintersteiner rosettes and photoreceptor differentiation (fleurettes). Rosettes are more common in eyes enucleated from very young infants. Tumors composed entirely of fleurettes (retinoma/retinocytoma) are thought to be retinoblastoma precursors, and like retinoblastoma, harbor mutations in both copies of the RB1 gene. Retinoblastoma is a major cancer treatment success story in developed countries where most deaths are caused by secondary tumors in germline mutation carriers. High-risk histopathological features that are an indication for adjuvant chemotherapy include massive uveal invasion and retrolaminar optic nerve invasion. Eye-sparing therapies including brachyradiotherapy and systemic and intra-arterial chemotherapy have reduced the number of eyes with retinoblastoma requiring enucleation in recent years.

P-0155 Incidental Carcinoma of Gallbladder: Audit of Experience From a Tertiary Care Cancer Centre in North India

ABSTRACT Introduction Laparoscopic cholecystectomy is the most common surgery performed for symptomatic benign gall bladder disease. Carcinoma may be detected after histological examination of simple cholecystectomy (laparoscopic / open) (called incidental carcinoma of gall bladder, ICGB). The incidence of ICGB ranges from 0.3 to 2.9%. According to literature, the incidence of carcinoma gall bladder is high in northern India and laparoscopic or open cholecystectomy is done widely in patients with benign gall bladder disease. There is limited literature regarding management and outcomes of ICGB. We performed an audit of patients undergoing exploration for radical cholecystectomy in patients with ICGB. Methods A retrospective review was performed of the data from the prospective maintained computerized database of all patients who have undergone simple cholecystectomy elsewhere and presented to the department of Surgical Oncology with ICGB from November 1995 to January 2009 for completion radical cholecystectomy. Statistical analysis was done using SPSS software. Descriptive analyses of the data were done. Chi-square test was used to compare proportions of categorical covariates. A p-value of 0.05 was considered significant. Kaplan-Meier analysis was done for survival analysis. Results Forty-two patients with incidental CGB were re-explored with plan for completion radical cholecystectomy. Eighteen (43%) and 24 (57%) patients had undergone laparoscopic or open simple cholecystectomy for benign gallbladder disease respectively. The median age was 46 years (range 25 to 69 years). M:F ratio was 1:6. The median time of re-exploration after initial surgery was 65 days (range of 19 to 145 days). Twenty-four (57%) patients were operable and underwent radical cholecystectomy. Eighteen (43%) patients were found inoperable due to locally advanced unresectable or metastatic disease. Thirteen patients with high-risk histopathological features received adjuvant concurrent chemoradiotherapy. Among the 24 patients who could undergo a completion radical cholecystectomy, 11 developed recurrence over a median period of 11 months. Finally 13 (31%) patients were alive and disease free at median follow-up time of 14 months (range 8-86 months).Those patients explored before 3 months had a decreased chance of having inoperable disease than those explored after 3 months (33% vs 67%, p Conclusion Incidental carcinoma of gall bladder is supposed to be associated with good prognosis group in-view-of early stage at detection. However, our experience has shown that approximately half of ICGB were operable at definitive surgical exploration and 1/3rd of those undergo exploration benefit in the long-term. The reason for this high recurrence may be due to spillage of bile and tumor during laparoscopic simple cholecystectomy, increased chances of locally advanced disease after a delayed re-exploration and highly aggressive disease. Re-exploration before 3 months have a better operability and recurrence free survival rate than after 3 months.

Presentation of retinoblastoma at a paediatric eye clinic in Ghana

Retinobalstoma, the commonest childhood malignant intraocular tumour, is usually diagnosed early with over 90% survival rate in developed countries. In developing countries, the diagnosis is late resulting in less than 50% survival. To determine retinoblastoma stages at presentation and patients' outcomes. Retrospective case series. The clinical and histopathological records of children with retinoblastoma seen from May 2004 to December 2005 were studied. Data was analysed for mode of presentation, laterality, clinical staging using Reese-Ellsworth (R-E) classification, histopathological high risk features (HHRF) for metastasis, and patient outcome. Ophthalmology Unit, Korle-Bu Teaching Hospital, Ghana. Twenty-three patients presented with retinoblastoma over the period. Males were 12(52.2%). The age range from 1 to 84 months, mean 36.3(±22.15) and median (36 months). Nineteen (82.6%) had unilateral and 4(17.4%) bilateral disease. The common clinical presentations were leukocoria in 20(87.0%), proptosis 8(34.8%), strabismus 5(21.7%) and red eye 5(21.7%). The clinical features were commensurate with R-E stage V in 20(87.0%) patients, 2(8.7%) with orbital recurrence and 1(4.3%) with post-enucleation anophthalmos. HHRFs were present in 9(75%) enucleated eyes with invasion of optic nerve as the commonest site (7/9). The patients were followed up for 1 day to 19 months. Eight abandoned treatment, 2 were discharged for palliative treatment, 2 out of 5 with metastasis died and 6 had no metastases at their last visit. Common sites for metastasis were the bone marrow, brain and orbit. Majority of the patients presented with advanced disease manifesting as leukocoria, proptosis, RE stages V disease and poor outcome.

Melanoma-associated retinopathy: A presenting sign of metastatic disease

To the Editor: A 57-year-old Caucasian man presented with a 1-month history of bilateral diminished visual acuity in low lighting environments (nyctalopia), photopsias, and decreased color discrimination. Four years before presentation, the patient was diagnosed with a superficial spreading melanoma of the left calf, Breslow thickness 1.0 mm, Clark level IV, without ulceration or high-risk histopathologic features. The wide local excision revealed clear surgical margins and sentinel node biopsy was declined.

The Inside Mystery of Jejunal Gastrointestinal Stromal Tumor: A Rare Case Report and Review of the Literature

Gastrointestinal stromal tumors (GISTs) are malignant and rare form of soft tissue sarcoma of the digestive tract. The incidence of gastrointestinal stromal tumors is very low Kramer et al. 2005 Jejunal GISTs are extremely rare. Here we present a rare case of jejunal GIST with unusually large size at presentation. The patient presented with severe abdomen pain, exophytic growth, and dimorphic anemia. Surgical resection of the tumor was carried out, and operative findings revealed a 15 × 10 cm growth, arising from serosal surface of jejunum, at the antimesenteric surface. Diagnosis in this case was made by subjecting the resected specimen to immunohistochemical analysis. In view of large size of the resected tumor, and high-risk histopathological features, imatinib mesylate 400 mg once daily was given as adjuvant chemotherapy. Patient is asymptomatic without any evidence of tumor recurrence after six months of postoperative followup. Imatinib as such is recommended in metastatic, residual or recurrent cases of GISTs or which are surgically not removable; however, recent recommendations suggests the use of imatinib mesylate after radical surgery in high-risk cases, because it has shown a significant decrease in the recurrence rate, and the Food and Drug Administration (FDA) has also approved the use of imatinib as adjuvant therapy after complete resection of localized, primary GIST.

Conjunctival melanoma: local-regional control rates, and impact of high-risk histopathologic features

Conjunctival melanoma is an uncommon malignancy with the potential for significant morbidity. Ulceration is known to be an indicator of more aggressive cutaneous melanoma. This factor has not been previously evaluated in conjunctival melanoma. Twenty-six patients with conjunctival melanoma who underwent excision by a single surgeon at a cancer referral center treated between June 2003 and July 2008 were included. The medical records were reviewed for clinical and pathological data. Outcomes assessed included local recurrence, regional lymph node metastasis, distant metastasis, use of adjuvant topical chemotherapy or adjuvant radiation therapy, final visual acuity and death. Local recurrence was seen in three patients (12%). Regional lymph node metastasis and distant metastasis were each seen in four patients (15%). Tumors >2.0 mm thick were more likely to develop distant metastasis than those with a thickness of <2.0 mm (p = 0.0331). Ulceration was noted in 10 of 26 patients. Regional lymph node metastasis and distant metastasis were each seen in 4 of 10 patients with ulceration, and none of the patients without ulceration. Ulceration in conjunctival melanoma may be an important histopathologic predictor of a more aggressive tumor. Globe-sparing multi-modality management of conjunctival melanoma can yield acceptable rates of local-regional recurrence.

Twenty‐nine Leydig cell tumors: Histological features, outcomes and implications for management

Leydig cell tumors are the most common interstitial neoplasm of the testes. Metastatic progression is historically quoted at over 10%, fuelling uncertainty as to the safety of testis sparing surgery. Between June 1998 and March 2009, 29 patients underwent surgery for Leydig cell tumor of the testis in our cancer network. We reviewed their histological features and clinical outcomes. Four patients with sub-5 millimetre lesions underwent testis sparing surgery and 25 were treated with radical orchidectomy. Histopathological characteristics that have been linked with risk of malignant progression were seen infrequently in our cohort: diameter greater than 50 mm, 0%; nuclear atypia, 14%; >3 mitoses per 10 high-power fields, 3%; infiltrative borders, 10%; necrosis, 3%; and vascular invasion 0%. No patient developed local or distant recurrent disease over a median follow up of 49 months, including seven and four patients disease-free at 5 and 10 years, respectively. The rate of metastatic progression is likely to be significantly less than 10%. Our data suggest that, in the absence of high-risk histopathological features, this tumor can be safely regarded as benign, pending a longer-term follow-up evaluation.

High-Risk Features and Tumor Differentiation in Retinoblastoma: A Retrospective Histopathologic Study

Certain histopathologic risk factors in enucleated eyes are important indicators for adjuvant chemotherapy in patients with retinoblastoma. To determine the frequency of histopathologic risk factors in a large series of retinoblastomas treated by enucleation on file in the pathology laboratory of a large American eye hospital, assess the relationship between tumor differentiation and age at enucleation, and investigate the frequency of photoreceptor differentiation and the role of retinoma/retinocytoma as retinoblastoma precursor. Retrospective histopathologic review of 387 eyes with retinoblastoma treated by enucleation including 297 with no prior treatment. Fifty-five of 297 untreated eyes (18.5%) had high-risk features. Retrolaminar optic nerve invasion was present in 31 (10.4%), and 24 (8.1%) had massive uveal invasion (defined as >3 mm in diameter). Of the high-risk eyes, 70.9% had iris neovascularization and 60% had neovascular glaucoma. There was a statistically significant inverse relationship between age at enucleation and the degree of tumor differentiation, evidenced by the presence of rosettes. Tumors in older children tended to be poorly differentiated, while rosettes were often numerous in the tumors of younger infants. In all, 20.4% of tumors contained foci of photoreceptor differentiation, which localized in the base of a predominantly endophytic tumor in about one-fourth. Lack of correlation between photoreceptor differentiation and age at enucleation is consistent with early or prenatal malignant transformation. Both preceding observations provide evidence for the hypothetical role of retinoma as a retinoblastoma precursor. Slightly less than 1 in 5 infants with retinoblastoma treated by enucleation at a large American eye hospital would require adjuvant chemotherapy on the basis of existing high-risk histopathologic features. Retinoblastomas become progressively less differentiated with time and may be spawned by precursor retinomas.

Adjuvant therapy for Colon Cancer

In patients with colon cancer who undergo resection for potential cure, 40% to 60% have advanced locoregional disease and are classified as either stage II or stage III. The role of adjuvant therapy in stage III colon cancer is well defined. The results from the MOSAIC trial (Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer) and the National Surgical Adjuvant Breast and Bowel Project C-07 trial confirm a definite disease-free survival (DFS) benefit with the addition of oxaliplatin to either infusional or bolus 5-fluorouracil/leucovorin (5-FU/LV). The Xeloda in Adjuvant Colon Cancer Therapy (X-ACT) trial showed capecitabine to be of equivalent clinical benefit to bolus 5-FU/LV. However, adjuvant trials with irinotecan, including Cancer and Leukemia Group B (CALGB 89803), the Pan-European Trial in Adjuvant Colorectal Cancer 3 (PETACC-3), and the French ACCORD trial, have not shown a significant DFS advantage. In contrast, in patients with stage II disease, a small survival benefit of 1% to 5% exists with chemotherapy. Perhaps the analysis of molecular markers in combination with high-risk histopathologic features will help increase patient specificity and identify subsets of patients with stage II colon cancer who will derive a survival benefit with adjuvant therapy. The current Intergroup study stratifying stage II patients based on presence of microsatellite instability and loss of heterozygosity 18q allele will help us better understand the risk versus benefit observed.

Do we need a new classification for radical hysterectomy? Insights in surgical anatomy and local tumor spread from human embryology

Objective. Current surgical treatment of cervical carcinoma is based on the assumption of undirected intra- and transcervical local tumor propagation and is executed by tailored excision of the paracervical tissues. We have recently demonstrated that cervical carcinoma spreads for extended phases during its malignant progression within the permissive compartment of the Müllerian morphogenetic unit (Lancet Oncol 2005;6:751–56) and proposed Müllerian compartment resection as the new principle for surgical treatment of cervical cancer. Do we need a new classification of radical hysterectomy? Methods. The therapeutic index of the surgical treatment of cervical carcinoma FIGO stages IB1–IIB by extirpation of the Müllerian compartment through total mesometrial resection (TMMR) without adjuvant radiation is evaluated by an ongoing controlled prospective trial at the University of Leipzig. Results. From 7/1998 to 12/2006, 163 patients with cervical carcinoma, FIGO stages IB1 ( n = 94), IB2 ( n = 21), IIA ( n = 14) and IIB ( n = 34) have been treated with TMMR and nerve-sparing therapeutic lymph node dissection. Twenty-five patients received (neo)adjuvant chemotherapy. No patient underwent adjuvant radiotherapy although 95 patients (58%) would have needed this additional modality in case of conventional radical hysterectomy because of their high-risk histopathological tumor features. At a median follow-up time of 45 months (3–104 months), recurrence-free and disease-specific overall survival is 93% and 96%. Maximum treatment-related morbidity according to the Franco-Italian score has been grade 2 in 12 patients (8%). Conclusions. The developmental view of local tumor spread and surgical anatomy holds a great promise for improving the therapeutic index of surgical cervical cancer therapy and challenges both the classification of radical hysterectomy based on tailored paracervical resection and the indication for adjuvant radiation.

Extensively Necrotic Retinoblastoma Is Associated With High-Risk Prognostic Factors

Retinoblastoma is the most common malignant intraocular tumor in children. It has been shown that adjuvant therapy following enucleation in patients with high-risk histopathologic features significantly decreases the mortality. We describe the association of extensive necrosis of tumor and intraocular structures with 2 of the major risk factors: optic nerve invasion and choroidal invasion. This may alert the pathologist who makes the observation of extensive necrosis to carefully search for histologic features associated with adverse outcome. To determine whether extensively necrotic retinoblastoma is associated with high-risk histologic prognostic factors for metastatic disease and patient survival. Retrospective case series. Forty-three eyes of 43 patients with retinoblastoma who underwent enucleation between 1990 and 2001 were evaluated. Medical records, histopathology specimens, pathology reports, and clinical photographs were reviewed. Tumors were designated as exhibiting extensive necrosis if more than 95% of tumor cells and intraocular tissues were necrotic. The main outcome measure was the association of extensive tumor necrosis with 3 high-risk histopathologic features: extraocular extension, optic nerve invasion, or choroidal invasion. Metastatic disease, patient survival, and associations with pathologic findings were also analyzed. Optic nerve head invasion (P < .001), post-lamina-cribrosal invasion (P < .001), and choroidal invasion by tumor (P = .004) were observed more frequently in eyes with extensive necrosis compared with eyes without extensive necrosis. Two of the 11 patients with extensively necrotic intraocular retinoblastoma died from metastatic disease (P = .06). None of the 32 patients without extensive necrosis developed metastatic disease or died. Extensive ocular tissue and tumor necrosis is associated with histologic high-risk prognostic factors for tumor metastasis and mortality.