New dolphin discovered in the Amazon surprises scientists.


Inia araguaiaensis
Inia araguaiaensis

 

 Researchers have discovered a new species of river dolphin from the Amazon. 


Writing in the journal Plos One, scientists led by Tomas Hrbek of Brazil’s Federal University of Amazonas formally describe Inia araguaiaensis, a freshwater dolphin that inhabits the Araguaia River Basin. It is the first true river dolphin discovered since 1918.

The discovery came after Hrbek and colleagues noticed that a group of river dolphins in the Araguaia was isolated from other Amazon dolphins by a series of rapids. Conducting genetic analysis, the researchers found the Araguaian boto (Inia araguaiaensis) to be distinct enough from other Amazon dolphins to be classified as a different species. The scientists estimate that the dolphin species diverged some two million years ago, corresponding to the separation of the Araguaia-Tocantins basin from the Amazon basin.

The differences between the Araguaian boto and their closest relatives, Inia geoffrensisand Inia boliviensis, extend beyond genetics. The Araguaian boto is smaller, has a different number of teeth, and has a wider skull.

Distribution map of all known species and subspecies of Inia.
Distribution map of all known species and subspecies of Amazon river dolphin Inia.

The new discovery has immediate implications for conservation. While river dolphins are generally not hunted directly in most of the Amazon due to local taboos, they do face risks from hydroelectric projects, pollution from urban areas and agriculture, boat traffic, and accidental bycatch. Moreover the Araguaian boto population is apparently quite low, according to the new research, which estimates the number of individuals at around 1,000.

“Populations of the middle and upper Tocantins River are fragmented by six hydroelectric dams, not including the Tucurui dam, and are likely to have very few individuals,” the authors write. “Since the 1960’s the Araguaia River basin has been experiencing significant anthropogenic pressure via agricultural and ranching activities, and the construction of hydroelectric dams, all of which have had negative effects on many biotic and abiotic aspects of the functioning of the Araguaia River ecosystem which I. araguaiaensis inhabits. Similarly I. araguaiaensis in the Tocantins River is affected by agricultural and industrial development, and is fragmented into isolated populations by hydroelectric dams. Interpreting these data using IUCN criteria, Inia araguaiaensis should minimally be considered vulnerable (VU Red List category).”

A vulnerable listing may force policymakers in Brazil to consider the species’ plight when planning new industrial developments in the basin. Brazil is currently in the midst of a dam-building spree throughout the Amazon Basin, which environmentalists warn could disrupt the ecological functioning of the world’s largest river system.

 

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Big old trees grow faster, hold more carbon


More tree, less carbon: A magnificent, spreading banyan tree that has grown through a dargah in Kondapeta near Giddaluru in Prakasam district of Andhra Pradesh. Photo: Kommuri Srinivas

More tree, less carbon: A magnificent, spreading banyan tree that has grown through a dargah in Kondapeta near Giddaluru in Prakasam district of Andhra Pradesh. Photo: Kommuri Srinivas
Large, older trees have been found to grow faster and absorb carbon dioxide more rapidly than younger, smaller trees, despite the previous view that trees’ growth slowed as they developed.

Research published in the journal Nature this week shows that in 97% of tropical and temperate tree species, growth rate increases with size. This suggests that older trees play a vital role in absorbing carbon dioxide from the atmosphere.

William Morris, a PhD candidate from the University of Melbourne involved in the study, says that prior to the study, the common assumption was that as trees aged, their growth rate and carbon absorption decreased. Morris explained that the belief came from two different lines of evidence:

“First, it has been shown that at the whole forest level, young forest acquires mass faster than old-growth forest. Second, studies have shown that the leaves of older trees are less efficient at photosynthesising than the leaves of younger trees.”

But the new study, which involved 403 tree species and was led by authors from the US Geological Survey, examined carbon storage at the level of individual trees rather than forests.The findings highlight the value of large, older trees, which have been declining in number, as important carbon sinks.

“Previously we thought of big old trees as simply carbon stores. But now we know that not only are they storing lots of carbon, they are also sequestering more carbon and faster than smaller trees,” said Morris.

Dr David Lindenmayer, a professor of environment at the Australian National University, described findings of the study as “immense”, with implications of global significance.

“It highlights another reason why it is really important that we grow as many areas of forest through to being old growth forests as possible,” he said.

“The more carbon we can store in forests, the more chance we have of reducing the mega-effects that are going to arise from massive climate change. Storing large amounts of carbon in forests is absolutely critical to that and the way you do that is you have big, old trees.”

Dr Bill Laurance, a professor at James Cook University’s Centre for Tropical Environmental and Sustainability Studies, agreed that the study reinforces the importance of large, older trees for absorbing carbon.

“That underscores the importance of saving old-growth forests, which harbour most big old trees, if we want to have the maximum benefit for slowing climate change,” he said.

The study is also expected to have implications for forest management plans. Morris explained that the new findings can change how individual trees are managed.

“As we now know that the biggest trees are the most valuable as both carbon stores and carbon sinks. If a manager’s goal is to maximise carbon uptake, then maintaining larger trees may be an efficient way to do so,” he said.

Dr Lindenmayer said the study highlights flaws in forest policy in Victoria and Tasmania of Australia, where old-growth forest is often cleared for pulp and timber purposes.

“Native forests, in terms of their value as carbon storage, significantly outweigh their value as pulp and timber. When you add that to the value of biodiversity and water, it’s pretty clear what forest policy should be,” he said.

The Conversation

 

This is the biggest fossil spider ever found.


 

This Jurassic spider has a body length of 1.65 centimeters (.65 inches) and a leg length of 5.82 centimeters (2.29 inches.)

 

Image credit: University of Kansas

Jurassic spider fossils used to be extremely rare finds. The first was discovered in Russia and described in 1984 —another was found three years later. But that remained the totality of the fossil record.

Then, in the twenty-first century, farmers in the area of Daohugou, China—just inside Inner Mongolia—began turning up Jurassic-period arachnids on a hillside. Because of the proliferation of these Chinese discoveries, these days a few hundred specimens are known to science.

“Village farmers dig pits to extract the fossils, which are mainly insects and the occasional spider or other animal, and experts from the university in Beijing travel there, usually during the New Year holiday, and sort through the finds,” says Paul Selden, professor of invertebrate paleontology with the department of geology at the University of Kansas.

Image credit: University of Kansas

Selden is part of a team that recently described the largest-known fossil spider ever unearthed. They report their findings in the latest issue of Naturwissenschaften.

This specimen’s body length is 1.65 centimeters, and its first leg length is 5.82 centimeters.

Part of the family?

“It’s unique because it’s intermediate between the more primitive kinds of the araneomorph, or ‘true’ spiders, and the well-known orbweavers that we see around us commonly today,” Selden says. “While it’s the largest known fossil spider, it’s not the largest spider, which is a Brazilian tarantula.”

The giant fossil spider is considered to be the male version of a female spider found a short time ago in the same locality, called Nephila jurassica. But because some of its physical characteristics are different from the Nephila genus, the latest discovery has spawned an entirely new scientific name.

“Because the male shows features that are not consistent with the placement of the species in Nephila or, indeed, the family Nephilidae, the species was given a new genus name and a new family erected to accommodate the new genus,” says Selden, who also serves as the Paleontological Institute’s director at the university’s Biodiversity Institute.

Tiny details

As with most fossil spiders, the features needed to precisely place the species among spider families were not sufficiently preserved. Scientists must have an exhaustive look at foot claws, hairs, and genital organs. As luck would have it, the volcanic ash beds at Daohugou are exceptional for preserving such fine details.

“Scanning electron microscopy came to the rescue with some of these features, such as the structure of the hairs, and helped to place the species more accurately,” says Selden. “This is the first time this technique has been used on fossil spiders in the rock.”

Selden says that one of the most interesting aspects of this study is how it relates to work being done in molecular systematics on living spiders. “This research relies on fossils to calibrate the data points and give an idea about when the genes for particular traits evolved,” he says.

“When the female was first placed in Nephila, it seemed to throw the existing family tree out of kilter. My colleagues doing the molecular work hypothesized that N. jurassica was actually a primitive orbweaver. Now, the discovery of the male and this detailed research has corroborated their predictions.”

Clues to the climate

He says that the discovery tells scientists that the abundant insect life in this area during the Middle Jurassic was preyed upon, as today, by large, web-dwelling spiders. Importantly, he says the find helps inform humans about its own future on the planet.

“First, it is an amazing spider,” Selden says. “It’s the largest fossil spider—and great to have both male and female. Second, research into the anatomy reveals details of how it lived and interacted with its insect prey.

“These give clues to what the climate was like at the time, and we can then track the fate of these ecosystems as they evolved through time and changing environments. Understanding the processes involved helps us to predict how manmade changes might affect the Earth’s climates and biodiversity.”

 

Pregnancy fat ‘may alter baby brain’


Pregnant women

A high-fat diet during pregnancy has the potential to alter a baby’s developing brain and increase its chances of obesity later in life, animal studies suggest.

The team at Yale School of Medicine, in the US, showed diet could change the structure of mice brains.

They argue this could explain why the children of obese parents are more likely to become grossly overweight.

Experts said the study had merit, but brain changes in humans were unproven.

Obesity can run in families and shared eating habits are a major factor.

However, there is evidence that diet during pregnancy can also influence a child’s future waistline, such as through changes to DNA.

‘Signal to the pup’

The latest foray into the field, published in the journal Cell, shows the structure of the brain itself may be changed.

“Start Quote

Twenty years of research shows nutrition in early life has lasting effects on cardiovascular disease, obesity, osteoporosis and some cancers. It’s extremely well established”

Dr Graham BurdgeUniversity of Southampton

The experiments on mice showed that mothers on a high-fat diet had pups with an altered hypothalamus, a part of the brain important for regulating metabolism.

These mouse pups were more likely to become overweight and develop type 2 diabetes than the pups of mothers given a normal diet.

One of the researchers, Prof Tamas Horvath, from Yale, told the BBC: “It could be a signal to the pup that it can grow bigger as the environment is plentiful in food.

“We definitely believe these are fundamental biological processes also affecting humans and influencing how children may eventually become obese.

“It seems, at least, that this could have a major impact and we need to explore it further in both animal and human studies.”

He says a healthy diet during pregnancy may help to break the cycle of obese parents having obese children.

‘Neurological circuits’

Commenting on the findings, Dr Graham Burdge, from the University of Southampton, told the BBC: “Twenty years of research shows nutrition in early life has lasting effects on cardiovascular disease, obesity, osteoporosis and some cancers. It’s extremely well established.

“This is an intriguing technical advance showing neurological circuits are being changed, which hasn’t been shown before.”

He said the “concept fits in well with the data” but pointed out there were key differences in the way mice and people process fat, so the same might not be happening in pregnant women.

He added: “Much of what we know about the process comes from animals. The next big thing is to establish the same mechanisms operate in humans and if we can modify that.”

For now he advises parents to “have a healthy balanced diet and ensure the diet of your child is balanced as well”.

Questionable Benefit From HPV Vaccine After Age 15.


Quadrivalent human papillomavirus vaccine may not protect a significant percentage of women against squamous intraepithelial lesions and other cervical dysplasias, according to a study published in the Journal of Clinical Oncology.

The Canadian researchers linked vaccination and cervical screening databases, among others, from the province of Manitoba to compare the incidence of cervical dysplasia in 3,541 women at least 15 years old when they were vaccinated with 9,594 aged-matched women who were not vaccinated. About 87% of the vaccinated subjects had more than one shot recorded in the three-shot series.

Among those women vaccinated between 15 and 17 years of age and followed for a median of 3.1 years, adjusted vaccine effectiveness (VE) was a nonstatistically significant 35% against high-grade squamous intraepithelial lesions (HSILs) and 21% against low-grade squamous intraepithelial lesions (LSILs). No protective effect was found (VE –1%) against atypical squamous cells of undetermined significance (ASCUS) (J. Clin. Oncol. 2014 Jan. 6 [doi: 10.1200/JCO.2013.52.4645]).

Among women 18 years or older with normal cervical cytology when vaccinated, the team estimated VE at a nonsignificant 23% against HSILs, and found no protective effect against LSILs (VE 18 %) or ASCUS (VE 20%). They found no evidence of protection among women with abnormal cervical cytology before immunization (VE 8%).

Both immunized and nonimmunized women had a cumulative 3-year probability of 2.8% for ASCUS. The vaccinated group had a cumulative 3-year probability of 3.3% for LSILs and 2.3% for HSILs; the unvaccinated group had a cumulative 3-year probability of 3.7% for LSILs and 2.6% for HSILs. Carcinoma-in-situ was detected in 12 vaccinated females (0.3%) and 22 unvaccinated females (0.2%).

“These findings affirm the importance of vaccinating females at a young age before any significant exposure to HPV occurs and underscores the need for maintaining organized high-quality screening programs that cover all sexually active women, even if they were vaccinated,” concluded Dr. Salaheddin M. Mahmud of the University of Manitoba, Winnipeg, and his associates.

Although in preapproval trials, the “vaccine was shown to be greater than 90% effective against HPV 16/18-associated dysplasia, VE in practice is likely much lower because these types are only responsible for approximately half of HSILs and a quarter of LSILs. Moreover, these high VE estimates were only observed in per-protocol analyses that were typically limited to HPV-naive women who received all three doses. In the intention-to-treat analyses, which were closer in design to our analysis, efficacy estimates were much lower, especially against HPV16-associated dysplasia. Efficacy was also lower among older women and among women with abnormal baseline Pap cytology; in one trial, VE was a mere 18.7% in the latter group,” they said.

Vaccinated women in the study were more likely to have Pap smears, leading to a possible detection bias; VE was a bit higher when the analysis was limited to women in both groups who had at least one Pap smear after enrollment.

The researchers added that “vaccinated women were also more likely to have been screened before enrollment, [which] may reflect increased concern … about the risk of sexually transmitted infections.”

Immunosuppressive Therapy Ups Risk for Skin Cancers.


Current and previous use of thiopurines, biologics, and combination therapies are all independent risk factors for skin cancer, according to expert analysis given at a conference on inflammatory bowel diseases.

Although population-based cohort studies have shown that the baseline risk for nonmelanoma skin cancer in IBD has risen more than a third since the preimmunomodulator era, regardless of the mode of treatment, “Cutaneous side effects of immunomodulators and biologics are a rising concern in clinical practice,” said Dr. Jean-Frederic Colombel of the Icahn School of Medicine at Mount Sinai in New York. “Patients with Crohn’s disease in particular have shown a twofold increased risk for nonmelanoma skin cancer, outside of any kind of immunomodulator or biologic therapy.”

Thiopurine use has been associated with a twofold increased risk of nonmelanoma skin cancer that persists even after withdrawal from the medication, although there is not an increased risk for melanoma, according to Dr. Colombel.

In a comparative analysis of studies published primarily since 2011, he noted anepidemiologic study with an A level of evidence for nearly 10,000 IBD patients undergoing thiopurine treatment that had an increased risk for NMSC with an odds ratio of approximately 2.2 (95% CI, 1.24-3.81).

“What is very important to note is that the risk of nonmelanoma skin cancer persists even after the antimetabolite has been stopped,” said Dr. Colombel, referring to data from the CESAME study that indicated, regardless of age, past and current thiopurine use was associated with higher incidence rates of NMSC.

To date, other immunomodulators have not been associated with NMSC, said Dr. Colombel. “What we are observing is quite specific to azathioprine.”

Thiopurines are not considered a risk factor for melanoma, said Dr. Colombel. He cited a study of records from a health care claims database for the period between 1997 and 2009. In the study, 209 melanoma cases were matched with 823 controls. Exposure to thiopurines was associated with an OR of 1.1 for melanoma. In that same study, patients exposed to biologics were found to have an increased risk of melanoma, although the risk was higher in patients with Crohn’s disease than those with ulcerative colitis (OR, 1.94 vs. 1.73).

Biologics may also increase the risk of NMSC, although currently the data are “controversial” said Dr. Colombel. “The results are more difficult to interpret.”

The risk for NMSC in IBD patients exposed to biologics was evaluated in three studies published between 2010 and 2013. One study indicated no significant increased risk for either past or current biologic use (OR 1.14, 95% CI 0.95-1.36).

Another study indicated a twofold increased risk for patients who’d withdrawn from biologic therapy (OR 2.07, 95% CI 1.28-3.33) and who had persistent use (OR 2.18, 95% CI, 1.07-4.46).

A third study showed a 2.3 increased NMSC risk (95% CI, 1.44-3.47).

In a meta-analysis published in 2013, the pooled relative risk for melanoma in IBD patients exposed to biologics was not shown to be significant (RR, 1.10).

Combination therapy has been found to increase the risk of NMSC nearly fourfold, said Dr. Colombel.

Even though more data are needed, Dr. Colombel said that all patients who are scheduled to start immunosuppression should be informed of the potential for dermatologic complications. “Personally, I am now sending all my patients to a dermatologist for a baseline evaluation,” he said.

A solitary hyperfunctioning thyroid nodule harboring thyroid carcinoma: review of the literature.


Abstract

Hyperfunctioning nodules of the thyroid are thought to only rarely harbor thyroid cancer, and thus are infrequently biopsied. Here, we present the case of a patient with a hyperfunctioning thyroid nodule harboring thyroid carcinoma and, using MEDLINE literature searches, set out to determine the prevalence of and characteristics of malignant “hot” nodules as a group. Historical, biochemical and radiologic characteristics of the case subjects and their nodules were compared to those in cases of benign hyperfunctioning nodules. A literature review of surgical patients with solitary hyperfunctioning thyroid nodules managed by thyroid resection revealed an estimated 3.1% prevalence of malignancy. A separate literature search uncovered 76 cases of reported malignant hot thyroid nodules, besides the present case. Of these, 78% were female and mean age at time of diagnosis was 47 years. Mean nodule size was 4.13 ± 1.68 cm. Laboratory assessment revealed T3 elevation in 76.5%, T4 elevation in 51.9%, and subclinical hyperthyroidism in 13% of patients. Histological diagnosis was papillary thyroid carcinoma (PTC) in 57.1%, follicular thyroid carcinoma (FTC) in 36.4%, and Hurthle cell carcinoma in 7.8% of patients. Thus, hot thyroid nodules harbor a low but non-trivial rate of malignancy. Compared to individuals with benign hyperfunctioning thyroid nodules, those with malignant hyperfunctioning nodules are younger and more predominantly female. Also, FTC and Hurthle cell carcinoma are found more frequently in hot nodules than in general. We were unable to find any specific characteristics that could be used to distinguish between malignant and benign hot nodules.

 

Introduction

Thyroid nodules are frequently-encountered entities in clinical practice, occurring with a prevalence of 4% by palpation [1], 33% to 68% by ultrasound examination [2,3], and 50% on autopsy series[4]. While approximately 95% of thyroid nodules are benign, certain historical, laboratory, and sonographic features raise the suspicion for malignancy [5]. As the initial step for evaluation of a thyroid nodule is measurement of serum thyroid stimulating hormone (TSH) [6,7], it is not uncommon for patients with a solitary thyroid nodule to be diagnosed with hyperthyroidism. In this setting, the thyroid nodule may represent a solitary hyperfunctioning thyroid nodule in an otherwise normal thyroid gland or it may represent a hyperfunctioning or nonfunctioning nodule occurring within a toxic multinodular goiter, within a Graves’ disease or destructive thyroiditis milieu, or in an individual with a less common cause of thyrotoxicosis [8]. Thyroid scintigraphy employs radioiodine (123I, 131I) or technetium-99m-(99mTc) pertechnetate in order to differentiate these diagnostic possibilities. The distinction is important, because hyperfunctioning nodules – also referred to as “autonomous,” “autonomously-functioning,” or “hot” nodules – are thought to only rarely harbor malignancy, such that fine needle aspiration (FNA) is not traditionally indicated in this circumstance [6]. Per the 2009 revised American Thyroid Association Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer, “Since hyperfunctioning nodules rarely harbor malignancy, if one is found that corresponds to the nodule in question, no cytologic evaluation is necessary” [6].

Here, we present the case of a woman with subclinical hyperthyroidism due to a hyperfunctioning thyroid nodule who was diagnosed with minimally-invasive follicular carcinoma after surgical resection. We also include our findings from a formal literature review on this topic, in which the historical, laboratory, and radiological features of similarly-documented cases were scrutinized to determine if there are features that differentiate hyperfunctioning thyroid carcinomas from solitary toxic adenomas. The results of a separate literature review aimed at estimating the prevalence of thyroid cancer within hot thyroid nodules are also presented. Our goal is to call attention to the fact that hyperfunctioning thyroid carcinomas are well-described in the literature (and also likely underreported), challenging the commonly-held notion that the hot thyroid nodule is very unlikely to be cancerous.

Materials and methods

A MEDLINE literature search of English-language studies published between 1950 and January 2012 with the terms, “thyroid cancer, hyperthyroidism, surgery,” “thyroid cancer, hyperfunctioning nodule, surgery,” and “thyroid cancer, hot nodule, surgery,” was performed to determine the reported prevalence of thyroid carcinoma in patients undergoing resection of solitary hyperfunctioning thyroid nodules. Another literature search, using the terms, “hyperfunctioning thyroid carcinoma,” “toxic adenoma, thyroid carcinoma,” and “hot nodule, thyroid carcinoma” was performed using MEDLINE and by reviewing the citations of relevant articles in order to collect data on reported cases of patients with a solitary thyroid nodule found to harbor thyroid carcinoma. Case series were included provided that at least some demographic and clinical details of individual subjects were described. A third MEDLINE literature search, using the terms “hot nodule,” “hyperfunctioning thyroid nodule,” and “autonomous thyroid nodules,” was performed to establish the demographic characteristics and nodule sizes of subjects with solitary hyperfunctioning thyroid nodules. In this third group, the available studies analyzed the group of hyperfunctioning nodules en masse and did not make a distinction between hyperfunctioning nodules that were benign and those that may have been malignant. Therefore, while the aggregate data from these studies most likely involved predominantly benign cases, a small number of malignant cases also may have been included. For this reason, we will subsequently refer to this group as “predominantly-benign” hyperfunctioning (or hot) nodules.

Weighted averages of data were calculated by assigning a “weight” to each study (based on the number of subjects in the study divided by the total number of subjects for all studies), multiplying each weight by the subject mean in the corresponding study, and then taking the sum of these products.

Results

Patient case

A 29-year-old teacher was referred to her local endocrinologist to evaluate a palpable left thyroid nodule. While she did not report thyrotoxic symptoms at that time, she was found to have a suppressed TSH. Thyroid scintigraphy revealed a hyperfunctioning left-sided thyroid nodule, and ultrasonography revealed it to be 2.4 cm in greatest dimension, isoechoic, and in the left lower lobe. A follow-up ultrasound one year later revealed an essentially unchanged nodule measuring 2.5 cm.

The patient presented to our institution the next year, at which time she endorsed tremors, anxiety, insomnia, and oligomenorrhea. She denied local compressive symptoms, history of radiation exposure, or family history of thyroid malignancy. Her only medication was a daily multivitamin. Her weight was 106 kg with a height of 1.7 m, blood pressure of 117/73 mmHg, and heart rate of 79 beats per minute. A 1.5 cm, firm, slightly tender nodule was palpated in the left lower lobe of the thyroid; it moved with swallowing. There was no evidence of cervical lymphadenopathy or thyroid bruit. The patient had a slight, fine tremor of the hands with normal biceps deep-tendon reflexes bilaterally.

Thyroid function tests revealed a suppressed TSH (0.005 mcIU/mL, normal 0.4 – 4.5 mcIU/mL) but normal free T4 (1.1 ng/dL, normal 0.9 – 1.8 ng/dL) and free T3 (3.5 pg/mL, normal 2.3 – 4.2 pg/mL). Thyroid peroxidase antibody testing was negative (0.4 IU/mL, normal < 9 IU/mL), as were thyroglobulin antibody (< 20 IU/mL) and thyroid stimulating immunoglobulin (< 1.0) testing. Thyroid ultrasound revealed a 2.6 × 2.7 × 2.6 cm predominantly solid, isoechoic left lower lobe nodule with internal hypervascularity within a slightly enlarged but otherwise normal-appearing thyroid gland (Figure 1A and B). 123I thyroid scintigraphy revealed a left lower lobe hyperfunctioning nodule with 24-hour uptake of 27% (Figure 1C).

thumbnailFigure 1. Imaging and histologic features of the hot nodule present in the case report subject. (A) Ultrasonography of the left thyroid lobe, demonstrating a 2.7 cm, predominantly solid, and isoechoic nodule. (B)Color Doppler evaluation reveals blood flow within the rim of the nodule and intraparenchymally. (C) 123I thyroid scintigram depicts a round left-sided focus of iodine uptake with suppression in the remainder of the gland, consistent with an autonomously-functioning thyroid nodule. (D) Histological evaluation reveals that the lesion is solitary, circumscribed and encapsulated. The follicular proliferation is surrounded by a rather thick fibrous capsule. The lesion demonstrates a predominant follicular pattern of growth without papillary cytologic features (hematoxylin-eosin stain; original magnification × 4). (E) A focal area is identified where the tumor invades through and into the fibrous capsule (hematoxylin-eosin stain; original magnification × 2).

After discussing with the patient the benefits and risks of radioiodine ablation versus surgical resection (left hemithyroidectomy), she elected for the latter, citing the reduced risk of permanent hypothyroidism as her main deciding factor. Histologic evaluation of the surgical specimen revealed a solitary, circumscribed, and well-encapsulated tumor measuring 2.5 × 2.5 × 2.2 cm without lymphovascular invasion or extra-thyroidal extension (Figure 1D). A focus was identified where the tumor penetrated and budded through the well-defined fibrous capsule, giving the diagnosis of minimally-invasive follicular thyroid carcinoma (Figure 1E) in the setting of background lymphocytic thyroiditis. Given the pathologic diagnosis, lobectomy was felt to be sufficient, and neither completion thyroidectomy nor radioactive iodine ablation was pursued in this patient. Molecular testing was performed on the surgical specimen for BRAF and KRAS mutations, both of which were negative. At her 6-month follow up appointment, the patient was symptomatically and biochemically euthyroid on low-dose levothyroxine replacement and showed no evidence of cancer recurrence.

Estimated prevalence of malignancy within hot thyroid nodules

In order to place the current case report in context, we have attempted to establish the prevalence of malignancy within hot thyroid nodules. This involved a literature search for surgical case series of solitary hyperfunctioning nodules managed by thyroid resection. A total of 14 relevant case series were uncovered. The earliest we found was from 1967 and included 79 hot nodules that underwent surgical resection; none of those cases were found to harbor thyroid carcinoma. Among the 14 case series, carcinoma rates of intranodular carcinoma ranging from 0 – 12.5% were noted, with a weighted total of 3.1% (Table 1). Of note, some of those case series also included cases in which thyroid carcinoma occurred outside of the hot nodule; however for the purposes of our review, such extranodular cases were not included in our estimated prevalence determination.

Table 1. Intranodular thyroid carcinoma prevalence in patients undergoing resection of solitary, hyperfunctioning thyroid nodules

Search for distinctive features of malignant hot thyroid nodules

We next sought to establish historical and/or clinical features that may help to differentiate malignant, hyperfunctioning thyroid nodules from benign, toxic adenomas, especially since hyperfunctioning thyroid carcinoma is generally an ex post facto diagnosis. Using the search criteria listed in the Methods Section, we discovered 76 cases (in addition to the current case) of malignant hot thyroid nodules, in which autonomy was highly suggested by both biochemical parameters of hyperthyroidism and scintigraphic evidence of increased radioiodine or labeled technetium uptake. All possibly-relevant features of the 77 cases were extracted and are displayed in Table 2, and a further analysis of these features appears in Table 3. An additional 27 cases with scintigraphic evidence suggestive of nodular autonomy but with normal thyroid function tests, absent thyroid function testing, or uninterpretable laboratory results (e.g., patients already on levothyroxine therapy at time of laboratory collection) were also found in the literature search (Table 4); these cases were excluded from subsequent analyses since autonomy seemed less certain.

Table 2. Reported cases of biochemically-hyperthyroid patients with a reported hyperfunctioning nodule discovered to harbor thyroid carcinoma on pathological review

Table 3. Demographic and clinical characteristics of the reported cases of hyperthyroid patients with hyperfunctioning thyroid carcinoma from the literature and the current case (n = 77)

Table 4. Additional cases with scintigraphic evidence suggestive of an autonomous thyroid nodule without documented hyperthyroidism (or already on levothyroxine replacement therapy) discovered to harbor thyroid carcinoma on pathologic review

Demographic characteristics

We compared age at diagnosis and female: male ratio of individuals with malignant, hyperfunctioning thyroid nodules to those with benign, toxic adenomas. Data on the latter group was compiled from a separate literature search which identified several surgical case series of predominantly-benign hot nodules, as described in the Methods section (Table 5). Subjects with malignant hot nodules were younger at the time of diagnosis than those listed in multiple case series of predominantly-benign hot nodules [47.0 vs. 57.6 years, respectively (Tables 3 and 5)]. Additionally, a greater percentage of subjects with malignant hot nodule were female as compared to those with predominantly-benign hot nodules [3.53:1 vs. 1.65:1 female to male ratio, respectively (Tables 3 and 5)].

Table 5. Demographic characteristics of patients with solitary hyperfunctioning thyroid nodules

Size

The sizes of the malignant hot nodules (Table 2) and predominantly-benign hot thyroid nodules are compared in Figure 2A. Of note, the clinical use of ultrasonography began in the late 1960s, so that the sizes listed in the early case reports of malignant hot nodule were estimated by palpation. We include tumors that were noted to encompass the entirety of the hot nodule as well as microcarcinomas embedded within a larger hot nodule. The actual size of the tumor within the thyroid nodule determined by pathological review was occasionally provided in the literature and is listed in Tables 2 and 4. The mean nodule size among the subjects with thyroid carcinoma was 4.13 ± 1.68 cm, which closely approximates the mean size of the predominantly-benign hyperfunctioning nodules.

thumbnailFigure 2. Size and biochemical assessment of hyperfunctioning thyroid nodules. (A) The mean greatest dimension of the malignant hot thyroid nodules from our case series is compared with that from five published surgical cases series of solitary, hyperfunctioning thyroid nodules. (B) The proportion of subjects with scintigraphically-determined hyperfunctioning thyroid carcinoma (Tables 2) who have frank biochemical hyperthyroidism vs. subclinical hyperthyroidism, based on varying nodule size. Subjects are characterized as having nodules < 2.5 cm (A), 2.5 – 4.5 cm (B), and > 4.5 cm (C) in diameter.

Biochemical profile

The majority of subjects with a malignant hot nodule demonstrated elevation of triiodothyronine (76.5%), whereas closer to half of the subjects had elevation of thyroxine (51.9%) (Table 3). Note that these percentages represent the number of subjects with an elevated thyroid hormone level (total and/or free value, depending on the particular study) divided by the total number of subjects with a hyperfunctioning thyroid nodule. Far fewer subjects had subclinical hyperthyroidism (13%) (Table 3). In comparison, with the exception of 3 studies, similar data on the biochemical profiles of subjects with benign, toxic adenoma in the collected case series were only sparsely included. In a study of 35 subjects with toxic adenoma, Hamburger found 16 with elevations in both T3 and T4 levels, 16 with elevations of only T3, 3 with isolated T4 excess, and 7 with subclinical hyperthyroidism [77]. In a study of 63 patients with solitary toxic adenoma, Langer found that mean free T3 level was significantly higher (8.8 ± 3.5 pg/mL, normal range 4 – 6.8 pg/mL) than mean free T4 level (16.9 ± 6.6 pg/mL, normal range 7 – 17.5 pg/mL) [78]. Blum evaluated 35 patients with solitary autonomous thyroid nodule and found that 65% had elevated T3 levels, 54 % had elevated T4 levels, and 31% were biochemically euthyroid [72]. Thus, hypersecretion of T3 appears to be a common factor among both benign and malignant hyperfunctioning thyroid nodules. Of interest, a greater prevalence of frank biochemical hyperthyroidism can be seen in patients with malignant hyperfunctioning thyroid nodules who have larger nodules (Figure 2B).

Historical and sonographic features

We next turned our attention to high-risk historical features and suspicious sonographic features to determine if these were present in cases of malignant hot nodule (Table 3). These features are described in Cooper et al. [6] and are listed in the Tables 2 and 3 legend. None of the 77 subjects with malignant hot nodules was noted to have high-risk historical features. Eleven subjects (36.7%) had suspicious features on ultrasonography, which is likely an underestimate, as some of the more newly-recognized high-risk sonographic features (e.g., taller than wide on transverse view) were not utilized in the earlier published reports. It was difficult to assess cases for nodule growth as a risk factor for malignancy, since the vast majority of the subjects were referred to surgery for immediate resection. However in seven cases, nodules were noted to grow over time. While an increase in nodule size is an indication for biopsy, the specificity of this finding for malignancy is limited, as 9-89% of benign nodules have been shown to grow over time depending on which definition for significant growth is used [21,73,77,79].

Histologic subtype

The majority of malignant hot nodules were proven to be PTC (57.1%), and of these, 18.2% were the follicular variant of PTC (FVPTC). Follicular thyroid carcinoma (as seen in our patient) comprised 36.4% of cases, while Hurthle cell carcinoma was found in 7.8% of samples. By comparison, in the U.S. National Cancer Data Base (1985–1995), which includes histologic information on all thyroid nodules as a group, the prevalence of PTC was approximately 85%, FTC was 10%, and Hurthle cell carcinoma was nearly 3% [80]. Thus, there does seem to be a higher prevalence of both FTC and Hurthle cell carcinoma in the hyperfunctioning thyroid carcinoma cases.

Of note, within the 77 identified cases of malignant hot nodule, only 23 subjects received FNA of their thyroid nodule prior to resection. FNA enabled a pre-operative diagnosis of thyroid carcinoma in 43.5% of cases. However, 30.4% of subjects undergoing FNA were erroneously characterized as having benign lesions, and 17.4% of samples were nondiagnostic. Of the subjects with false negative biopsies, surgical pathology eventually revealed PTC in 3 cases (one of these was FVPTC), FTC in 1 case, and Hurthle cell carcinoma in 3 cases. Tumor size was given in only 3 instances of false negative biopsies. Two of these were of subcentimetric PTC, and it is presumed that small size was likely a chief factor leading to misdiagnosis. However, the other was a 3 cm nodule comprised wholly of Hurthle cell carcinoma.

Discussion

To our knowledge, the current data set is the largest and most detailed to date of patients with malignant hot thyroid nodule. In that regard, this study complements the informative and excellent 2012 review by Pazaitou-Panayiotou and colleagues examining the association of thyroid carcinoma with a broader spectrum of hyperthyroid states, including Graves’ disease and toxic multinodular goiter in addition to hyperfunctioning thyroid nodule [81]. Of note, although it was not the focus of the Pazaitou-Panayiotou et al. review to perform a detailed analysis of the historical and clinical features of malignant hot nodule cases, as we did here, Pazaitou-Panayiotou and colleagues did include an evaluation of thyroid carcinoma prevalence. The reported percentages of thyroid carcinoma in their collected case series of patients with hot nodules, which overlapped but did not mirror exactly those case series evaluated here and which also included some cases of thyroid carcinoma occurring in extranodular thyroid tissue, ranged between 2.5 – 12.0%. This corresponds to a weighted average of 6.9% and thus is similar to the 3.1% prevalence estimated here. In its discussion of thyroid carcinoma in patients with hyperfunctioning nodules, the Pazaitou-Panayiotou et al. review also included several other important commentaries. For instance, they draw attention to two studies suggestive of a higher prevalence of thyroid carcinoma in hot nodules occurring in children [82,83], though the latter study included children from an iodine-deficient region. In addition, they discuss several reports in which activating mutations of the TSH receptor gene were identified within malignant hot nodules [81].

There are several noteworthy discussion points and implications to the findings presented here. The first relates to the prevalence of malignancy within solitary hot nodules. As mentioned, in the available surgical case series that addressed this topic, a varied prevalence was noted, ranging from 0 – 12.5%, with a weighted average of 3.1%. Only a minority of the patients who underwent surgery in those series did so because of concerning findings from FNA, and as such, we do not believe that the data set is biased towards cases in which a post-operative diagnosis of malignancy was expected. We realize that this collection of case series includes only a small fraction of the total number of solitary hot nodules that have occurred, and also that the vast majority of malignant hot nodules likely have gone unreported. Furthermore, it is likely that malignancy goes undiagnosed in many cases of hot nodules treated with radioiodine, especially those harboring microcarcinomas. Despite these limitations, we do believe there are sufficient numbers of cases included among the collected 14 surgical case series of subjects to cite the 3.1% figure as being a fair and representative estimate of malignancy prevalence amongst solitary hyperfunctioning nodules. While this 3.1% prevalence figure is low – and in fact is lower than the estimated 5 – 15% prevalence of malignancy among all thyroid nodules [6] – it is not trivial. Thus, the possibility of malignancy within a hot nodule must not be overlooked by a managing clinician, particularly if management other than surgical resection is chosen.

Another important discussion point regards the limitations resulting from the retrospective nature of this analysis, including incomplete data and differing methodology used in many of the collected case reports and case series of malignant hot nodule. While some of the primary sources were meticulous in their case descriptions, others included less-thorough descriptions. For example, tumor size was frequently not reported, and thus it was unclear if a PTC tumor was simply an incidental microcarcinoma embedded within a larger hot nodule or a large, follicular variant of PTC comprising the entirety of the nodule. While we have included some cases in which the malignancy was a microcarcinoma and thus of uncertain clinical significance [84], these cases are clearly in the minority (only 8 of the 77 reported tumors were less than one centimeter in size). Other factors affecting the data set are the evolution of technology and our understanding of risk factors for thyroid carcinoma. For instance, thyroid ultrasound began clinical use in the late 1960s, and prior to this, nodule size was estimated by palpation. Earlier reports would not have commented on some of the suspicious sonographic features recognized today. Additionally, the radioimmunoassays used to measure TSH have undergone many generations of refinement over the past several decades, and thus the presence and degree of hyperthyroidism may have been underestimated in earlier studies.

Also worth discussing are the differential prevalences of thyroid carcinoma histologic subtype found in hot nodules as compared to nodules as a group. As mentioned, there was a much higher prevalence of both FTC and Hurthle cell carcinoma in hot nodules (36.4% and 7.8%, respectively) as compared to in all nodules (10% and nearly 3%, respectively). Additionally, a substantial percentage of the PTC cases found in hot nodules were the follicular variant. This may have bearing on the current algorithm for evaluation of patients with thyroid nodules as recommended in the 2009 thyroid nodule and thyroid carcinoma management guidelines [6]. In particular, for those nodules found by biopsy to have follicular neoplasm by histology, the guidelines recommend consideration be made for performing an 123I thyroid scan, if not already done, especially if the serum TSH is in the low-normal range; if the nodule is found to be hyperfunctioning, it can then be followed [6]. However, the high prevalence of both FTC and FVPTC reported for malignant hot nodules suggests that a biopsy diagnosis of follicular neoplasm within a hot nodule may not be as reassuring as previously thought. Also of interest, in a 2009 study, Sundaraiya and colleagues reported a case of metastatic FTC occurring in the setting of thyrotoxicosis, in which high-grade extrathyroidal uptake of technetium-99m-pertechnetate was observed; in a literature search, they found 74 other cases of thyrotoxicosis resulting from well-differentiated thyroid cancer metastatic lesions, most of which demonstrated histologic evidence of FTC [85].

As a final point of discussion, since none of the historical, biochemical or radiologic characteristics that were assessed seems to predict malignancy in the collected cases of hot nodules, one might ask if there is any utility in biopsying hot nodules. Such would be a shift from the current thyroid nodule management guidelines which views an increased nodular radiotracer uptake pattern as a reassuring characteristic from a cancer perspective [6]. Given the estimated 3.1% prevalence of malignancy within hot nodules, and also taking into account the difficulty in predicting whether a particular hot nodule is malignant, we recommend that hot nodules that are not treated surgically (as is an option to manage the hyperthyroidism) be considered for biopsy if high-risk historical and/or suspicious sonographic features are present or if these nodules grow over time, just as is currently recommended for nodules that are not hyperfunctioning [6]. This should also include previously hyperfunctioning nodules treated with radioiodine, although the known occurrence of dystrophic calcification and cystic degeneration as sequelae of radioiodine ablation should be taken into account when assessing their sonographic features [86]. Future prospective studies could help determine if biopsying at the time of diagnosis all hot nodules with suspicious sonographic characteristics and/or associated high-risk historical features versus biopsying hot nodules only if the initial sonographic characteristics worsen over time would result in better outcomes.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

SM performed the literature review and drafted the manuscript. DM provided the radiology images and participated in drafting/revising the manuscript. LP provided the pathology images and participated in drafting/revising the manuscript. SW helped to provide the surgery perspective and edited the manuscript. JZ assisted with the literature review and drafting of the manuscript. All authors read and approved the final manuscript.

Acknowledgements

The authors would like to acknowledge Jeffrey R. Garber, M.D. for helpful discussions. We also acknowledge the support of the Diana and Richard C. Strauss Professorship in Biomedical Research and the Mr. and Mrs. Bruce G. Brookshire Professorship in Medicine at UTSW Medical Center.

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Hot thyroid nodules can sometimes be cancer.


A woman presented with hyperthyroidism. Her TSH was <0.01.  Radioactive iodine uptake and scan revealed an area of increased uptake on the right with suppression of the surrounding thyroid tissue consistent with a hyperfunctioning nodule (see figure #1).

Figure 1. Hyperfunctioning right thyroid nodule.

A thyroid ultrasound confirmed a nodule in this region.  The nodule was hypervascular, which would be consistent with a hyperfunctioning nodule. However, the nodule was also markedly hypoechoic with areas of calcification (see image #2). Because of the ultrasound findings, a fine needle biopsy was done, which identified a follicular lesion on cytology.

Because of the biopsy findings, the patient chose to undergo total thyroidectomy instead of radioactive iodine therapy. To everyone’s surprise, this nodule turned out to be a follicular thyroid cancer.  She subsequently was treated with radioactive iodine ablation. Since then, she has done well without evidence of residual cancer.

Most of us were taught that thyroid nodules that are hyperfunctioning or “hot” on radioactive iodine scan are very rarely — or almost never — cancer. This risk of cancer in a hyperfunctioning nodule is indeed rare. Because of this, guidelines suggest against biopsying hot nodules.  However, a recent literature review identified that of solitary hyperfunctioning thyroid nodules which were surgically resected, 3.1% were malignant.  Most were follicular or Hürthle cell cancers.

Figure 2. Ultrasound of hyperfunctioning thyroid nodule.

Some experts have advised against ordering thyroid ultrasound in hyperthyroidism because it would be unlikely to change management and would add cost and risk to patient care because it would result in unnecessary biopsies of benign thyroid nodules.

Although I agree with that opinion in general, I would not recommend primary care practitioners routinely order a thyroid ultrasound in the evaluation of every single patient with hyperthyroidism, I also believe there are exceptions. Furthermore, as I have posted before, when ultrasound is performed by an experienced thyroidologist, there are situations when ultrasound can be useful in evaluation of hyperthyroidism.

As clinicians, we must remember that even if the chances of something may very unlikely, that does not mean that it is absolutely impossible. Guidelines are meant only to be a guide; they are not rules written in stone.  The challenge for clinicians of course is to determine which nodules would benefit from further evaluation, while at the same time avoiding biopsying every single nodule “just because it’s there.”

How to Turn Your Big Dream into a Joyful Reality.



“When you are inspired by some great purpose, some extraordinary project, all your thoughts break their bonds: Your mind transcends limitations, your consciousness expands in every direction, and you find yourself in a new, great and wonderful world. Dormant forces, faculties and talents become alive, and you discover yourself to be a greater person by far than you ever dreamed yourself to be.” ~ Patanjali

I don’t know about you, but there is something almost magical about having a big dream! A dream so vivid that you can almost taste it. A dream so big that it draws a smile to your face each time you allow yourself to think of it. When dreams are this GOOD we often keep them close to our heart because they are soooo blissful that sharing them might in some way taint them. You know what I mean?

Last December I was sitting in my newly purchased home in Portland Oregon doing my vision-board exercise (I say “annual” as though I do this each year…I think this was only my 2nd year!). I was looking out the window at the dreary day and although I was grateful for my new house…I KNEW that I couldn’t spend another winter in the dreary Northwest.

The only thing that brought a twinkly to my eye on a day so dreary was my BIG dream of moving to Mexico for the Winter. Unlike most people who save tropical paradise for their 60’s, I wanted it NOW (yesterday to be exact). This dream seemed pretty un-doable. I had just bought a house and even though I had started my consulting practice I wasn’t exactly profiting enough to quit my part-time/stable job.

I finished my vision board that day and spent the next month getting more clear on a plan to make my dream happen. I’m happy to say that not only will I be spending all Winter in Mexico this year, I also got married this summer and just got back from 2 months traveling all over Asia with my new husband! It’s been a magical year and I want to share 5 tips with you that I found essential in getting from where I was…to where I am.

How to turn your big dreams into reality and live the happy and meaningful life you truly deserve:

1. Dream Big & Dream Vivid

It may sound cliche, but if you can’t dream it, you won’t get it. So before you start putting together some half-assed plan to “make your life better”, allow yourself some “dreamin’ time” to get really clear on what you ACTUALLY want. I did a vision board (as many people do), but most of my dreaming happened in a special journal that I would bring around with me and work on when I could. About once a month I would go up to a great indoor hot springs in Oregon where I could be alone with my thoughts, swim, nap, draw and journal. That’s what worked for me…but you need to figure out what works for you!

When you dream big envision very vividly what you want, where you are, who you are with and how you want to feel. Don’t just write “I want to live in Mexico”. Cut out pictures on Mexico, envision eating food and smelling the ocean with your partner. Have some fun with this!

2. Set a Timeframe

Depending on your dream this could be 1 week or 10 years! I recommend selecting a timeframe that is realistic (so that you don’t set yourself up for disappointment), but also not too far out (so that you don’t lose sight).

I set my goal as 1 year away. I knew I wanted to spend next Winter in Mexico and I knew that I needed to build up my business enough to quit my job and work remotely.

3. Make a Plan

I don’t consider myself an abundance coach, but I have had great success with creating abundance in my life. I think it is because I dream big and then I actually make a plan to make it happen. Depending on your dream this could look like many things.

I created a step by step process where I figured out what I wanted and went backwards. So because I wanted to live in Mexico in one year (while working remotely), I had to make growing my business a main objective with well-defined income markers to help me then set goals of how many clients I needed to work with.

You see how that worked? I took a BIG dream and took that main barrier standing in my way (income for while I lived in Mexico) and broke it down into monthly goals so that I could quit my job and be ready to work in Mexico within a year. I also had to get a renter in my house to pay my mortgage while I was away, so I applied the same process to figuring out what steps I needed to take to make that happen (pack house, take pictures, post on rental site and interview renters, etc).

If you think having a vision board is enough, you will forever be disappointed…make your plan and make it measurable! If you’re not good at this, hire someone to help you! I help people all the time create strategy plans with business and your life is no different!

4. Share your dreams, drop your expectations

Here’s the deal; people don’t always have your back or want you to succeed. The fact that you have a dream can be enough to make people extremely uncomfortable. You could handle this by not telling anyone your dream or you could learn to manage how you take in negative feedback from others.

I used to share my dreams with people and be really disappointed if they didn’t react exactly how I wanted them to react (though I couldn’t quite articulate how I wanted them to react). This created an emotional roller coaster where I would feel excited when I was alone and alone when I shared my dreams to a room full of naysayers. Sometimes negative feedback is enough to completely mess with the dreamers head and throw them off course. This is BAD!

Instead I want YOU to change your mindset and your expectations…because at the end of the day, that is all you have control over.  So when you share your dreams and you are met with crickets, odd glances, or rude remarks realize one thing…its about THEM, not YOU. Your dreams are so big that they scare them (and that’s pretty cool!).

I can’t even begin to tell you all the stories where I had to apply this principle. If I had let all the naysayers have their way, I would be stuck in dreamy Portland drowning my Mexico dreams in watered down margaritas (no bueno!)

5. Make room for your dream to become a reality

This tip is something that can be applied to everything above. If you want something to enter your life (wether it’s a couch or a new job), you have to make space for it. If your current group of friends is totally unsupportive of your new dreams and your sick of having to manage your expectations, make room for other friends to enter your life who are there to support you.

If you want to launch a business, but you work full-time, you need to figure out a way to make space in your schedule to work on your new biz (whether it means cutting back in hours at work or cutting down on your “free time” activities).

Call it energy or whatever you like, if you make room for something, it will enter your life a lot sooner! Letting go so that you can get more can be scary, but give it a shot with something small to start out! You might be surprised what happens.

I hope you found my tip sheet helpful and inspiring enough to get you dreaming big (and acting fast!) If you have a big dream and you want to share it with a supportive community, then share in the comments section!

USPSTF Gives Final Recommendation on Lung Cancer Screening.


Low-dose computed tomography screening of those at high risk for lung cancer has received a grade B recommendation from the U.S. Preventive Services Task Force. Initially available for public comment in July 2013, the Task Force’s recommendations are now final and published.

The action allows the Centers for Medicare and Medicaid to mandate this service be provided without charging a copay or deductible. Widespread availability of screening raises concerns about inappropriate use of low-dose computed tomography (LDCT) and the associated costs of the procedure, physician experts noted in editorials and interviews.

More than a third of Americans are current or former smokers. Increasing age and cumulative exposure to tobacco smoke are the leading risk factors for lung cancer.

The USPSTF defines those at high-risk patients as heavy smokers who are aged 55-80 years and have a 30-pack-year or more habit, and former heavy smokers who have quit in the past 15 years. Screening should be discontinued once a person has not smoked for 15 years.

Patients also can be selected for screening based on risk factors other than tobacco use, including occupational exposures, radon exposure, family history, and incidence of pulmonary fibrosis or chronic obstructive lung disease.

Because of the potential for patients to experience “net harm, no net benefit, or at least substantially less benefit” from screening, the USPSTF stated it may be inappropriate to screen patients who have comorbidities that limit life expectancy, or who would be either unwilling or unable to have curative lung surgery.

Other forms of screening, including chest x-rays and sputum cytology, are not recommended because of their “inadequate sensitivity or specificity.”

The USPSTF’s recommendations are based largely on a systematic review of several randomized, controlled trials published between 2000 and 2013, including the National Lung Screening Trial. That study of more than 50,000 asymptomatic adults, aged 55-74 years, showed a 16% reduction in lung cancer mortality and a 6.7% reduction in all-cause mortality when patients were screened using LDCT. One cancer death was averted for every 320 patients screened, and one death from all-causes was prevented in every 219 patients screened.

“Lung cancer causes as many deaths in the United States as the next three leading types of cancers combined, all of which already have screening interventions,” wrote Dr. Frank C. Detterbeck of Yale University in New Haven, Conn., and Dr. Michael Unger of the Fox Chase Cancer Center in Philadelphia in an editorial accompanying the report.

And while the use of LDCT is part of a structured screening process, not just a scan, the USPSTF report does not address many of the practical aspects of implementing lung cancer screening, they said.

Many patients who are not necessarily high risk will present to their physicians with anxiety about developing lung cancer. “These people have reasons for their concerns; turning them away because they do not meet the criteria does not provide them the reassurance they seek,” the editorialists wrote. An educated discussion usually eases the patient’s fear, but “this requires specialized knowledge and time. It is easier to give in and screen an anxious patient who does not meet the criteria.”

As noted by the USPSTF, the potential harms of LDCT screening include false-negative and false-positive results, including the potential for incidental findings, overdiagnosis, and radiation exposure. “In a high-quality screening program, further imaging can resolve most false-positive results; however, some patients may require invasive procedures,” the recommendations state.

Dr. Detterbeck and Dr. Unger wrote that effective screening hinges on reaching high-risk individuals, yet this is the population least likely to seek screening despite recognizing they are at risk. Further, chest CT is not a simple way to provide reassurance to anxious, lower-risk individuals. It is questionable whether primary care physicians will have the time and skill to advise patients on lung cancer screening and whether the “health care system is willing to support what the USPSTF is recommending.”

Dr. Peter B. Bach, director of the Center for Health Policy and Outcomes at Sloan-Kettering Cancer Center in New York, authored a second editorial that accompanied the recommendations.

In an interview, he noted that issues of cost and counseling “matter a lot now that the Affordable Care Act links these recommendations to mandatory insurance benefits, which will then lead to automatic increases in health insurance premiums,” according to Dr. Bach.

What is needed, he said, is more granular level of recommendations with more clinical utility.

“The expected degree of net benefit or level of certainty about the evidence is rarely uniform, even for selected populations,” he wrote in his editorial. There are subgroups in which we have a lot of insight that screening is quite a bit more likely to help than harm, and the findings from the NLST should drive the approach.

Across the quintiles of lung cancer risk studied in the NLST, those considered to have experienced a probable benefit from screening varied from 5,276 in the lowest-risk group to 161 in the highest-risk group. Similarly, when considering the NLST’s benefit-to-harm ratio across the quintiles from lowest to highest, the number of false-positive results per lung cancer–related death prevented varied from 1,648 false-positive results per prevented death to 65, respectively, he said.

Screening protocols for patients in the low-risk group should receive a grade C from the USPSTF, which means the service should be offered selectively only, according to Dr. Bach.

“Screening should not be mandated for insurance coverage in the low-risk population. Neither should doctors and patients be told that it is definitely a good idea for everyone, nor should it become a quality standard for doctors, hospitals, and insurance plans, which are all things that could happen with this “B” recommendation,” Dr. Bach said in an interview.

Dr. Bach was the lead author of practice guidelines issued jointly in 2013 by the American College of Chest Physicians and the American Society of Clinical Oncology. Those guidelines, which are based mostly on the NLST, state that individuals aged 55-74 years who have at least a 30 pack-year smoking history should be screened with LDCT. The American Cancer Society has also endorsed lung cancer screening recommendations based on the same protocols as the ACCP and ASCO (CA Cancer J. Clin. 2013;63:107-17).

“I support the task force’s role in the crafting of essential health benefits absolutely,” Dr. Bach said. “But I think their power now to create mandates means they should up their game.”