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HousecallsUnderwriting Case Studies & Insights

Inside this issue

September 2015

Our Casebook

Case #1 – Choroidal Nevus ............................................. Pg. 2

Case #2 – Gallbladder Polyps .......................................... Pg. 5

Puzzler ........................................................................... Pg. 7

EditorMatthew Hughes704.344.4210mhughes@scor.com

By Richard Braun, MD

Dr. Braun is Vice President & Chief Medical Officer for SCOR Global Life Americas. He received a Bachelor of Science degree from the Towson State University (1975) and earned his medical degree from the University of Maryland (1979). Dr. Braun is board certified in Internal Medicine, Insurance Medicine and is a past President of the American Academy of Insurance Medicine.

By Richard Braun, MDVice President & Chief Medical Officerrbraun@scor.com The cases presented in this issue follow a common theme. Both involve possible

“incidental” findings that could evolve into very rare but serious malignancies. As medical imaging and investigations become increasingly available and less invasive, the underwriter is confronted with these situations more frequently.

One could argue that such rare conditions are covered by the underlying expected mortality built into insurance products. But this ignores the fact that the person had symptoms, sought treatment, and – armed with the additional knowledge – applied for insurance.

So, is there a way to estimate mortality associated with these findings?

We start with the medical literature, but always must be aware of referral bias. Simply stated, most medical journal submissions are from academic, tertiary care centers. In our first case study, the two reference studies (Lane, et al and Shields, et al) were conducted at such centers. Of the hundreds of thousands of choroidal nevi seen by optometrists and ophthalmologists across the USA, these few thousand cases were referred to such centers for their expertise. These are the high-risk cases. However, these high-risk cases are useful for identifying characteristics of the “incidentalomas” that predispose them to potential malignant evolution.

The lesson: be aware of the source of the medical study – is it community-based or from a tertiary referral center? Apply the findings accordingly.

The estimates ultimately will depend on the information provided in the research articles. Ideally mortality outcomes will be based on the findings. Perhaps there are only conversion rates, which then necessitate estimates based on conversion linked to predicted mortality of any future malignancy. Compliance with follow-up and early detection are two factors that would mitigate the mortality risk of any future malignancy.

Cases with multiple variables affecting estimates are challenging, and more than other more straightforward cases rely on the “Art of Underwriting.” We are interested in your feedback and welcome e-mails on these cases. With your permission we might share some of your opinions in future issues. ∞

Housecalls – September 2015 – 2

By Richard Braun, MD Vice President & Chief Medical Officer

A 43 year-old male applies for life insurance. He recently complained of seeing “floaters” when in bright sunlight and consulted an ophthalmologist. The examination revealed a choroidal nevus in the left eye. The nevus measured 6.2 mm in diameter and .25 mm in thickness. The eye examination was otherwise normal. Plans were made for follow-up in one year. Personal and family history were negative for melanoma.

QuestionWhat is the relationship of choroidal nevus to ocular melanoma, if any? Is there any extra mortality anticipated in this case?

AnswerThe choroid is a vascular layer of the eye that is sandwiched between the retina and the sclera. It is part of the uveal tract which contains melanocytes (pigmented cells containing melanin). The uveal tract also includes the iris and the ciliary body. Any part of the uveal tract can develop melanoma, however, 86% of reported cases arise in the choroid (Figure 1).

Choroidal nevi were found in 6.5% of Caucasian adults participating in a screening study in Australia. Estimates in the white US population range from 4.6%-7.9%. A recent review of participants (n=5575) undergoing retinal imaging as part of the 2005-2008 National Health and Nutrition Examination Survey (NHANES) provided a more detailed breakdown of the prevalence of choroidal nevi by age, sex, and race. The prevalence is higher in males, Caucasians, and those over age 60 (Figure 2). Overall, the prevalence was 4.7%.

The obvious underwriting concern about a choroidal nevus is that it may transform into an ocular melanoma. Fortunately, this is a rare occurrence. It is estimated that uveal tract melanoma occurs in 6-7 per million persons in the US. Analysis by Singh, et al used the prevalence of choroidal nevus and the incidence of choroidal melanoma from the Surveillance, Epidemiology, and End Result (SEER) database and

Case #1Choroidal Nevus

Figure 1 – Schematic of the Eye

The uveal tract is made up of the iris, the ciliary body and the choroid. The choroid is the vascular layer between the retina and the sclera.

Figure 2 – Prevalence of Choroidal Nevi by Age, Gender and Race

Observed prevalence of choroidal nevi in US adults from the 2005-2008 NHANES study, stratified by age, gender and race. The prevalence is likely underestimated because the imaged areas were focused on the macula and the optic nerve, which represent about 40%-45% of the total choroidal area.

Age, years

40-49 4.7%

50-59 3.1%

60-69 5.4%

70-79 6.6%

>80 7.5%

Gender

Male 5.0%

Female 4.4%

Race

White 5.6%

Black 0.6%

Hispanic 2.7%

Other 2.1%

Housecalls – September 2015 – 3

calculated a 1 per 8845 annual conversion rate from choroidal nevus to choroidal melanoma. The authors of the study note that the estimate may be high due to the potential for underestimation of the prevalence of choroidal nevi. Indeed, cancer of the eye is rare, since the most recent (2012) SEER data places the incidence of cancer of the eye and orbit for Caucasians age 75+ at 3.8/100,000; 65-74 at 3.26/100,000; and 50-64 at 1.7/100,000.

Much research has gone into identifying characteristics of cutaneous nevi to identify or predict current or future melanoma. This has resulted in the mnemonic ABCDE:

• Asymmetrical shape• Borders that are irregular• Color that is variegated or uneven• Diameter over 6 mm• Evolution denoted by changes in

color or size

The presence of any of these characteristics should prompt a consult with a dermatologist and consideration for possible biopsy.

In another study, Shields, et al suggest another helpful mnemonic: “To Find Small Ocular Melanoma Using Helpful Hints.” The beginning letters represent:

• Thickness > 2 mm• Fluid (presence of subretinal)• Symptoms (flashing lights and floaters)• Orange pigment• Margin (within 3 mm of the optic disc)• Ultrasonographic Hollowness• Halo (absence of)

The hazard ratio for choroidal nevus transforming to ocular melanoma for each characteristic is listed in Figure 3.

When combinations of factors were studied it was determined that the hazard ratio for the development of ocular melanoma with 1 or 2 factors was ~3; for 3 or 4 factors, ~5; for 5 or 6 factors, ~9; and for all 7 factors, 21.

Growth of a lesion over time is recognized as an important feature of melanoma, especially within a

short period. However, it should be noted that slow growth can occur in a benign nevus, and lesions that eventually develop into melanoma can be stable for decades prior to conversion. In one study the mean growth rate in lesions that developed into melanoma were .96 mm/year in diameter and 1.12 mm/year in thickness.

If it should develop, choroidal melanoma is a dangerous malignancy. Disease-specific survival rates after the diagnosis of uveal melanoma have been reported as 69% at 5 years, 55% at 15 years and 48% at 25 years. Tumor size, both diameter and thickness, have a relationship to mortality. A meta-analysis of uveal melanoma found all-cause mortality at 5 years for tumors <3 mm thickness to be 16%, for tumors 3 mm-8 mm thickness, 32%, and at >8 mm thickness, 53% (Figure 4, next page). Tumor thickness is strongly positively correlated to metastatic disease, with thicker tumors being more likely to metastasize.

Another study (Lane, et al) included a cohort of 1063 patients who had either a definite choroidal nevus, an indeterminate pigmented lesion, or a small melanoma. Choroidal nevi were <6 mm in diameter, <0.5 mm thick and did not have orange pigment, subretinal fluid, or symptoms at presentation (n=256). Indeterminate lesions were between 0.5 mm-2 mm thick and did not have orange pigment, subretinal fluid, or symptoms

Characteristic Parameter Hazard Ratio P Value

Halo Absence of surrounding halo 6.48 .009

Fluid Presence of subretinal fluid 3.16 .002

Hollowness Hollow by ultrasound 2.92 <.001

Orange Pigment Presence of orange pigment 2.75 <.001

Symptoms Flashing lights/floaters 2.34 .002

Thickness >2 mm* 2.09 <.001

Margin Within 3 mm of the optic disc 1.82 .001

* As a continuous variable there is an increase in hazard ratio of 2.75 for each 1 mm increase in thickness.

Figure 3 - Factors Predictive of Growth of Choroidal Nevi into Melanoma

Based on 2,514 patients with choroidal nevi followed at a tertiary care center. This may have been a high-risk group with a history of dysplastic nevus syndrome in 1%, cutaneous melanoma in the opposite eye in 4%. (Arch Opthalmol. 2009; 127(8): 981-987.)

Housecalls – September 2015 – 4

Choroidal Nevus (cont.)

at presentation (n=334). The remaining group was diagnosed with small melanomas (lesions <10 mm in diameter and <5 mm thick, n=373). Small melanomas were treated with radiation, as were nevi (n=3) and indeterminate lesions that evolved over time (n=39).

Authors of the study followed all subjects using the Social Security Death Master File and the National Death Index to determine cause of death. No patients in the choroidal nevus group died of ocular melanoma in the average 8.4 years of follow-up. In contrast the indeterminate group recorded 2 deaths, and 13 subjects within the small melanoma group died during the same observation period. In the indeterminate group cumulative disease-specific death rates by years of follow-up were 0 at 5 years, 1% at 10 years, and 3% at 15 years. One interesting finding was that the combined nevus and indeterminate lesion groups had 4 deaths from cutaneous melanoma during the follow-up period. This was 13 times the expected death rate from cutaneous melanoma in the general population.

Diagnosis and Treatment99% of choroidal pigmented lesions are diagnosed visually with the ophthalmoscope with occasional addition of ultrasonography. Studies are under way to determine other methods to distinguish between indeterminate lesions that have a high probability of progressing to melanoma from those that do not. Single-photon emission computed tomography (SPECT) using a tracer that accumulates in cells

producing melanin has shown promise. Analysis of high-resolution digital images and quantification of the autofluorescence of lipofuscin, the source of the orange pigment seen with ocular melanoma, has also shown promise in the detection of early ocular melanoma.

Ocular melanoma usually is treated with radiation or enucleation. Indeterminate or suspicious lesions are often followed closely, since treatment would likely result in the loss of functional vision (60%) or endanger the viability of the globe.

Returning to the CaseBy the numbers one can see that the overwhelming majority of choroidal nevi do not develop into melanoma. However, the presence of symptoms, absence of a surrounding halo, and the lesion diameter of 6.2 mm would make this case a slightly higher risk for future evolution to ocular melanoma. Based on 2 of these factors (symptoms and diameter) the case would have been classified as an indeterminate lesion in the study by Lane et al. They observed a disease-specific death rate of 1% at 10 years and 3% at 15 years. The thinness of the lesion and the overall rarity of ocular melanoma temper the overall risk. From the 2008 VBT, a 43 year-old male nonsmoker would expect 18.57 deaths per 1000 through duration 15 years. The additional disease specific deaths based on the study would represent an additional 162% mortality. Mild to moderate excess mortality would be the initial assessment. With compliance on future follow-up and demonstrated stability of the lesion, the risk should decrease. ∞

Referenceshttp://seer.cancer.gov/faststats/ last accessed 8/14/2015.

Lane AM, et al. “Mortality After Diagnosis of Small Melanocytic Lesions of the Choroid.” Arch Ophthalmol 2010. 128(8):996-1000.

Sheilds C, et al. “Choroidal Nevus Transformation Into Melanoma: Analysis of 2514 Consecutive Cases.” Arch Ophthalmol 2009. 127(8):981-987.

Grassetto G, et al, “Ocular Melanoma and Other Unusual Sites.” PET Clin. 6 (2011) 79–89.

Figure 4 – Ocular Melanoma

In this picture of a retina arrows indicate presence of ocular melanoma involving the optic disc.

Housecalls – September 2015 – 5

A 67 year-old male is applying for $1 million of life insurance. Records reveal he was recently evaluated for epigastric pain. After an abdominal ultrasound and blood work evaluation he was diagnosed with GERD. He responded well to typical reflux management and became asymptomatic. The ultrasound of the abdomen revealed a solitary 1.3 cm gallbladder polyp. There were no other abnormalities seen in the gallbladder, including absence of stones. It was felt to be an incidental finding. There was no family history of cancer. He was referred to a gastroenterologist for further evaluation of the polyp, but that consultation was not available at the time of application.

QuestionWhat are the mortality considerations of an incidentally discovered gallbladder polyp?

AnswerLesions projecting into the gallbladder cavity from the gallbladder wall are referred to as gallbladder polyps. Gallbladder polyps can be malignant or benign, although most are benign. Benign polyps can be pseudotumors such as cholesterol polyps, inflammatory polyps, or tumors such as adenomas, fibromas, lipomas, or leiomyomas. The most common

benign polyp is the cholesterol polyp (up to 70%). The most common malignant polyps of the gallbladder are adenocarcinomas (3%-8% of all polyps).

It is not uncommon to see gallbladder polyps mentioned in the imaging results of proposed insured applicant’s records. There are several contributing factors. First, abdominal pain is a common presenting complaint to physician’s offices. Second, ultrasonography imaging technology (US) is a commonly used medical test that is relatively inexpensive, readily available and felt to be safe. Third, the incidence of gallbladder polyps in

Case #2Gallbladder Polyps

By William Rooney, MD, FAAFP, EMBA Vice President, Medical Director

Dr. William (Bill) Rooney is Vice President, Medical Director at SCOR Global Life Americas. Dr. Rooney’s responsibilities include facultative case review work, researching and updating SOLEM®, researching and writing articles for a variety of SCOR publications

and more. He earned a medical degree from the University of Missouri – KC (1981) & an Executive Master’s in Business Administration from Benedictine College in Atchison, Kansas (2009). He is board certified in Family Medicine with the American Board of Family Medicine.

Albertus D, et al. “Autofluorescence Quantification of Benign and Malignant Choroidal Nevomelanocytic Tumors.” JAMA Ophthalmol. 2013. 131(8):1004-1008.

Qiu M, et al. “Choroidal Nevus in the United States Adult Population.” Ophthalmology 2015. Published online awaiting print: 1-13.

Singh A, et al. “Estimating the Risk of Malignant Transformation of a Choroidal Nevus.” Ophthalmology 2005. 112(10):1784-1789.

UpToDate® last accessed 8/14/2015.

Figure 1 – Gallbladder Polyp

A lesion projecting into the gallbladder cavity from the gallbladder wall (arrow) is referred to as a gallbladder polyp.

Housecalls – September 2015 – 6

Gallbladder Polyps (cont.)

the general population, according to many citations, is between 3%-7%. Finally, the US is considered very sensitive in detecting gallbladder polyps.

The underwriter’s dilemma is determining whether there is a significant risk for malignancy when a gallbladder polyp is mentioned in the records. This distinction is especially important because of the typically poor prognosis of gallbladder cancer. While a rare malignancy (about 4,000 new cases per year in the US) gallbladder cancer unfortunately is not usually discovered until it is in an advanced state (approximately 20% found in early stage). The overall prognosis for gallbladder cancer is poor, with a five-year survival rate of approximately 10%.

Moreover, completely ruling out an early cancer when a polyp is found is difficult. However, some characteristics increase the likelihood of cancer:

• The polyp is greater than 1 cm in size• The individual is 50 years old or older• The presence of a solitary polyp, a symptomatic

polyp, or concurrent gallstones

The presence of any of the conditions above increases the chance for malignancy. Additionally, thickness of the gallbladder wall in association with a gallbladder

polyp has been found to be associated with malignancy (Figure 3).

Diagnosis and TreatmentSerial imaging is commonly recommended when small polyps with no risk factors are discovered. If there is a strong suspicion of possible malignancy, surgical removal is commonly advocated. This is especially true since surgery is the only potentially curative therapy for gallbladder cancer and early-stage treatment is imperative to increase survival.

Returning to the CaseIn this particular case the finding of a gallbladder polyp should be of significance to the underwriting team. While we acknowledge that most polyps are benign there are several issues in this case which raise concern about the possibility of current or future malignancy. The polyp size (1.3 cm) and the age of the individual (67 years old) increase the chance for malignancy. Finally, the investigation and recommendation from the clinical team is incomplete and it would be prudent to await full evaluation of this abnormal US finding prior to an offer. ∞

Incidence 3%-7% of the general population

Clinical expression

Typically asymptomatic and found incidentally

Diagnosis Histological examination is the only definitive test

CourseSome shrink or disappear completely over time; most are stable and remain asymptomatic

SignificanceTypically benign. However, it can be secondary to cancer especially when...

- Age > 50; size > 1 cm

- Solitary polyp

- Concurrent gallstones

- Symptomatic polyp

Prognosis If cancerous, typically a poor prognosis

If benign, generally favorable

Figure 2 – Facts about Gallbladder Polyps

Size> 1 cm (43%-77% chance of malignancy)> 2 cm (almost always malignant)

Individual’s age > 50 years old

# of polyps Solitary are of more concern

Symptoms Symptoms are of concern

Gallstone presence Concurrent gallstones are of concern

Gallbladder appearance

Increased gallbladder wall thickness is concerning

Comorbid conditions

More concern when associated with sclerosing cholangitis

Figure 3 – Gallbladder Polyps: Characteristics of Concern

Housecalls – September 2015 – 7

ReferencesBaltayiannis, N. et al. “Gallbladder polyps: Diagnosis and treatment.” Hellenic Journal of Surgery. 2010 Aug.

Corwin, Michael T. et al. “Incidentally detected gallbladder polyps: Is follow-up necessary: Long-term clinical and US analysis of 346 patients.” Radiology. 2011 Jan; 258. P 278-82

Koga, A. “Diagnosis and operative indications for polypoid lesions of the gallbladder.” Arch. Surg. 1988; 123; 26.

Lee, KF, et al. “Polypoid lesions of the gallbladder.” Am. J Surg. 2004; 188(2): 186-90.

Saleh, Huain, et al. “Polypoid lesions of the gallbladder: Diagnostic and management challenges.” J. Gastrointestin Liver Dis. 2008 Sep; 17(3) 251-3.

http://www.cancer.org/cancer/gallbladdercancer/detailedguide/gallbladder-key-statistics. Accessed 2/19/15.

Zakko, Wisam, et al. “Gallbladder polyps and cholesterolosis.” UpToDate. Accessed 6/15/15.

By William Rooney, MD, FAAFP, EMBA

In this issue of the Puzzler Dr. Rooney presents another EKG. What is the major abnormality presented in this EKG?

To find the answer, be sure to visit the Housecalls page on www.scorgloballifeamericas.com. Click on the “September Puzzler” Powerpoint presentation to confirm your findings. ∞

Underwriting Puzzler...

The information conveyed and the views expressed in this newsletter are provided for informational purposes only and are based on opinions and interpretations made by SCOR Global Life Americas (formerly SCOR Global Life US Re Insurance Company). The opinions and interpretations expressed by SCOR Global Life Americas may not be the only interpretation available. This publication should not be copied or shared with any other company, reinsurer or consultant without obtaining prior approval from SCOR Global Life Americas.

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