National Cervical Screening Management GuideDr Jason Stone, QML Pathology

INSIDE THIS ISSUE:> National Cervical Screening

Management Guide

> Merkel Cell Carcinoma: An Update

> Subclinical Hypothyroidism in Early Pregnancy: An Update

A BRIEF OVERVIEW

Cancer Council Australia has recommended significant changes to the National Cervical Screening Program. The new 2016 Guidelines will replace the 2005 NHMRC Guidelines.

From December 2017, the Pap smear process will now be known as the Cervical Screening Test. The cervical cells will be collected in the same way as previously collected for Pap smears, with the only difference being that the sample is to be placed in a ThinPrep® vial with liquid media rather than smeared onto glass slides. Testing the sample for oncogenic Human papillomavirus (HPV) will replace cytology as the primary screening process. Liquid-based cytology (LBC) will be performed on the sample

by the laboratory if the HPV test is positive (i.e. reflex cytology) or in specific clinical circumstances (i.e. HPV and cytology co-test).

The cervical screening program will be available to women between the ages of 25 and 74 years. Women over the age of 25 will be invited by the National Cancer Screening Register to participate in the new National Cervical Screening Program. The recommended interval between cervical screening tests will change from 2 to 5 years.*

Women who have had the HPV vaccination must still participate in the screening program.

A detailed explanation of the program is available from Cancer Council Australia.

From 1st December 2017 the new National Cervical Screening Guidelines will take effect.

If you would prefer to receive the newsletter electronically, please email info@qml.com.au

ISSUE 4, 2017

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FEATURE ARTICLE

HPV TESTING

Human papillomavirus is a common virus. Most infections are harmless and resolve spontaneously in about a year. In some patients, persistent infection with one of the oncogenic genotypes of HPV can lead to cervical pre-cancer or cancer. Types 16 and 18 are more virulent than other HPV types, consistently causing around 75% of all cervical cancers.*

Testing for oncogenic HPV types has been shown to be as sensitive as cytology in identifying women at risk of developing cervical neoplasia. However, it is the strong negative predictive value of HPV testing that has the most clinical use.*

QML Pathology will use the latest HPV testing technology for the detection of the 14 HPV genotypes known to be associated with cervical cancer. The test specifically detects HPV 16 and 18 (which cause 75% of cervical cancers) while simultaneously detecting the 12 other oncogenic genotypes. There is an internal control which minimises the risk of false negative results for each patient.

Remember, a positive HPV result does not necessarily indicate that the woman has cervical neoplasia, but does indicate an increased risk.

ROUTINE 5-YEARLY CERVICAL SCREENING

For women aged 25 to 69

Depending on the result of the HPV, and any additional reflex cytology testing, women are assigned a clinical risk category – Low Risk, Intermediate Risk or Higher Risk. Each risk category follows a different clinical pathway. (Please see flowchart of pathways below):

Cervical Screening Pathways1. Low Risk = the HPV test is negative → The woman will be invited to rescreen in five years

2. Intermediate Risk = the HPV test is positive for one of the other oncogenic HPV types (i.e. NOT 16/18) and the reflex cytology performed by the lab is either negative or only shows low grade changes.

→ The woman will be invited to have another HPV test in 12 months

→ If the repeat HPV test in 12 months is negative then the woman can return to routine 5 yearly screening

→ If the repeat HPV test in 12 months is positive (regardless of type) then referral to colposcopy is advised

3. Higher Risk:

→ If the test is positive for HPV 16/18 then referral for colposcopy is advised (regardless of the result of the reflex cytology)

→ If the test is positive for other oncogenic HPV types (i.e. NOT 16/18) and the reflex cytology performed by the lab shows possible or definite high grade changes then referral for colposcopy is advised

Low Risk

Intermediate Risk

High Risk

102

6. CerviCal SCreeNiNg gUiDeliNeS

MANAgEMENT OF ONCOgENIC hPv TEST RESuLTS

EvIDENCE-BASED RECOMMENDATION gRADE

REC6.6: Positive oncogenic HPV (not 16/18) test result at routine screeningWomen with a positive oncogenic HPv (not 16/18) test result, with a lBC report of negative or prediction of plSil/lSil, should have a repeat HPv test in 12 months.

C

PRACTICE POINT

REC6.7: Referral of women with a positive oncogenic HPV (not 16/18) test result and LBC prediction of pHSIL, HSIL or any glandular abnormality

Women with a positive oncogenic HPv (not 16/18) test result, with a lBC prediction of pHSil/HSil or any glandular abnormality, should be referred for colposcopic assessment at the earliest opportunity, ideally within 8 weeks.

Flowchart 6.1. cervical screening pathway for primary oncogenic HPv testing

LEgEND

Risk of cervical cancer precursors

Primary test

Reflex test

Test result

Recommendation

Low

Intermediate

higher

reflex lBc

HPv detected (16/18)

UnsatisfactoryHPv test

pHsil/HsilUnsatisfactory lBc

negative

repeat HPv test in 12 months

HPv detected (any

type)

HPv notdetected

reflex lBc

retest for lBc only

within 6 weeks

HPv detected (not 16/18)

HPv notdetected

plsil/lsil

Oncogenic HPV test with partial genotyping

refer for colposcopic assessment

any lBc result or unsatisfactory

reflex lBc

routine 5-yearly

screening

routine 5-yearly

screening

retest HPv within

6 weeks

refer forcolposcopicassessment

Flowchart 6.1. Cervical screening pathway for primary oncogenic HPV testing. *Source: National Cervical Screening Program: Guidelines for the management of screen-detected abnormalities, screening in specific populations and investigation of abnormal vaginal bleeding. Cancer Council Australia, Sydney (2016)

FEATURE ARTICLE

For women aged 70-74

• If the routine screening HPV test is negative, then the patient is discharged from the screening program and no further screening is required.

• Any positive oncogenic HPV result (regardless of type) should be referred for colposcopy in this age group.

• Women aged 75 years or older who have never had a cervical screening test, or not had one in previous five years may request a test and be screened.

Test of cure for women with treated high-grade intraepithelial lesion (HSIL)

• HPV testing and cytology co-testing should be performed at 12 and 24 months post treatment.

• Once a woman has tested negative by both tests on two consecutive occasions, she is regarded as passing the Test of Cure and can safely return to the normal five-yearly screening interval.

• Any positive test for HPV 16/18 or a cytology result of possible HSIL or HSIL should be referred back to colposcopy.

Follow-up of women treated for Endocervical Adenocarcinoma in-situ (AIS)

• The follow-up of women treated for AIS is annual HPV and cytology co-test indefinitely.

• Any abnormal result will require referral back to colposcopy.

• Currently, the clinical evidence does not support a Test of Cure for endocervical lesions as there is for squamous lesions.

• It is important to inform the pathology laboratory if a woman has a history of AIS so that the appropriate cytology co-test is performed and the appropriate clinical recommendation can be made.

Screening after hysterectomy

• If the hysterectomy was for benign reasons (e.g. fibroids) and there was no history of cervical abnormality, then no follow-up is required.

• If the hysterectomy was for benign reasons (e.g. fibroids) and the cervical screening history is not available, then two consecutive negative HPV tests, 12 months apart, are advised before no further testing is required.

• Any woman with a hysterectomy and a history of HSIL is advised to pass the Test of Cure (as described previously). The Test of Cure can be done either prior to or after the hysterectomy. Once the Test of Cure is passed, then no further follow-up is required.

• Any woman with a hysterectomy and a history of Endocervical AIS should have annual HPV and cytology co-testing indefinitely as described in the previous section.

• Women who have undergone a subtotal hysterectomy (the cervix is not removed) should be invited for 5-yearly HPV testing in accordance with the recommendation for the general population.

Immune-deficient women

• Women with human immunodeficiency virus (HIV) or a solid organ transplant should have 3-yearly HPV Screening tests.

• Immune-deficient women with any positive oncogenic HPV result (regardless of type) should be referred for colposcopy.

• It is important to inform the pathology laboratory if a patient is immune-deficient so that the appropriate clinical recommendation can be made.

Screening in diethystilbestrol (DES) exposed women

• Women exposed to DES in utero should be offered an annual HPV and cytology co-test indefinitely.

• Any abnormal result will require referral back to colposcopy.

• Self-collection is not recommended.

• It is important to inform the pathology laboratory if a woman has a history of DES exposure so that the appropriate cytology co-test is performed and the appropriate clinical recommendation can be made.

Investigation of abnormal vaginal bleeding

• Women with abnormal vaginal bleeding should be offered an HPV and cytology co-test.

• Regardless of the test results, referral to gynaecological assessment for investigation of the bleeding should be considered.

• It is important to inform the pathology laboratory if a woman has clinical symptoms so that the appropriate cytology co-test is performed and the appropriate clinical recommendation can be made.

For women under 25 years old

• Routine cervical screening is NOT recommended for asymptomatic women under the age of 25 years.

• For women who experience first sexual activity at a young age (<14 years) and had not received the HPV vaccine before becoming sexually active, a single HPV test between age 20 and 24 can be considered on an individual basis.

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FEATURE ARTICLE

SPECIMEN COLLECTION FOR CERVICAL SCREENING

The collection of cervical cells is completed the same way a usual Pap Smear was collected, with the only difference being that the cervical cells are now placed in a ThinPrep® vial, rather than on a slide.

1. Obtain an adequate sample from the cervix

a) Use luke warm water to lubricate and warm the speculum. A water soluble gel lubricant can be sparingly applied to the posterior blade if necessary. Do not use carbomer-based lubricants.

b) Insert the speculum.

c) Insert the central bristles of the Cervical Brush deep enough into the endocervical canal to ensure the shorter bristles contact the exocervix, then push gently and rotate the broom in a full clockwise direction 4 - 5 times.

Please note: An Endocervical Brush should not be used in pregnant women.

2. Place the Cervical Brush into the ThinPrep® vial ASAP

a) Ensure the ThinPrep® vial is within the use by date. It can be stored at room temperature.

b) Push the Cervical Brush into the bottom of the vial 10 times, ensuring to push hard enough to force the bristles apart.

c) Swirl the Cervical Brush before removing it from the vial.

d) Discard the Cervical Brush.

Please note: Do not make any glass slides.

3. Secure the cap on the vial

Tighten the cap enough that the torque line on the cap is in line with the torque line on the vial.

4. Record patient details and complete request form

a) Record patient’s full name and date of birth on the vial.

b) Complete the patient’s details on the request form providing as much information as possible.

Pertinent clinical details are essential for reliable cervical screening.

Please request Cervical Screening Test, Routine in screening cases and Cervical Co-test, Symptomatic for symptomatic cases.

Other important information should be noted on the request form under clinical notes.

Doctor please consider:

• Patients who are symptomatic (e.g. history of abnormal vaginal bleeding) require both an HPV and a concurrent liquid-based cytology (LBC).

• Patients who have previously been diagnosed with Endocervical AIS, also require a concurrent LBC annually.

• Patients who are immune deficient are advised to repeat testing in 3 years not 5 years.

5. Package the sample and request form for transport

Place both the vial and request form into a specimen bag for transport to the laboratory in the usual manner.

SELF-COLLECTION

• Self-collection with a dry flocked swab is available for patients who have never been screened (>30 years old) or are under-screened (>30 years old and >2 years overdue for cervical screening).

• The accuracy of self-collected samples is limited compared to practitioner-collected samples and therefore self-collection is not advised as an alternative for women who would otherwise participate in the screening program.

• If the HPV result is positive, the woman may be referred for colposcopy or may have to return for a second sample (this time practitioner-collected) so that a LBC sample can be taken.

• For more information on self-collection see the Self-Collect - HPV Specimen Collection for the Cervical Screening Program available at qml.com.au.

TURNAROUND TIME

Results will be released to the requesting Doctor approximately 2-3 days after the sample is received by the laboratory.

COST

Cervical screening requests that follow the national prescribed clinical guidelines will be bulk billed subject to Medicare guidelines and criteria.

If Medicare guidelines and criteria are not met, an out-of-pocket fee may apply. If the patient wants additional cervical cytology smears that do not fit the MBS criteria, these tests will not be rebated by Medicare.

FURTHER INFORMATION

BRISBANE Dr Jason Stone MBChB FRCPath FRCPA - Cytopathology Head of Department T: (07) 3121 4444

Dr Stephen Peyton BAppSci MBBS FRCPA - Consultant Cytopathologist T: (07) 3121 4444

SUNSHINE COAST Dr Ethan Oost MBChB FRCPA - Consultant Cytopathologist T: (07) 5441 0200

GOLD COAST Dr Darina Vuong MBBS(Hons), BSc, FRCPA - Consultant Cytopathologist T: (07) 5668 4444

QML PATHOLOGY UPDATES

What do I put on the Pathology Request Form?

To meet Medicare guidelines and criteria, it is important that you complete the pathology request form correctly. The request form also plays a vital role in ensuring the laboratory performs the correct test and offers the correct clinical recommendation. Below are guidelines for requesting depending on clinical scenario.

ASYMPTOMATIC PATIENTS

Most patients will fall in this category, and will have no significant previous history or symptoms. For these cases, please clearly request “Cervical Screening Test, Routine” on the pathology request form. The laboratory will do HPV testing and/or liquid-based cytology as appropriate.

SYMPTOMATIC PATIENTS

Patients of any age who are symptomatic (e.g. abnormal vaginal bleeding) may require cervical co-testing (i.e. HPV + Cytology) as part of their investigations. In these cases, it is important that you very clearly state “Cervical Co-Test, Symptomatic” on the pathology request form. In addition, description of the relevant symptom (e.g. post-menopausal bleeding) would be helpful.

FOLLOW UP OF PREVIOUS ABNORMAL CERVICAL SCREENING TEST RESULT

If your patient’s previous Cervical Screening Test showed a positive HPV result and follow up testing was recommended, please clearly state “Cervical Test, follow up of previous abnormal result”.

TEST OF CURE

Patients with previously treated high grade squamous intraepithelial lesion (HSIL or CIN2/3) require 2 consecutive negative HPV tests, and negative cytology tests 12 months apart, before they are considered to be cured and can go back to routine 5-yearly screening. In these cases, please state “Cervical Co-Test, Test of Cure”.

PREVIOUS ENDOCERVICAL ADENOCARCINOMA IN SITU (AIS)

Patients with previously treated AIS require annual co-testing. Please state “Cervical Co-Test, Previous AIS”.

CYTOLOGY ONLY

“Cytology Only“ should be requested when patients have had a previous positive HPV test from a self-collect sample or a previous unsatisfactory cytology result. Please state ‘Cytology Only” as patients are not eligible for a second HPV test under these circumstances.

MEDICARE CARD NUMBER

PATIENT LAST NAME GIVEN NAMES

PATIENT ADDRESS POSTCODE

TEL (HOME & MOBILE) TEL (BUS)

DATE OF BIRTH FILE No.SEX

PATIENT LAST NAME GIVEN NAMES

PATIENT ADDRESS POSTCODE

TESTS REQUESTED

PATIENT COPY

TEL (HOME & MOBILE) TEL (BUS)

DATE OF BIRTH FILE No.SEX

REQUESTING DOCTOR (PROVIDER NUMBER, SURNAME, INITIALS, ADDRESS)

REQUESTING DOCTOR (PROVIDER NUMBER, SURNAME, INITIALS, ADDRESS) COPY REPORTS TO:

HOSPITAL/WARD

TESTS REQUESTED

LABORATORY COPY CLINICAL NOTES

STANDARD PRECAUTIONS PRIVATE & CONFIDENTIAL CUMULATIVE

URGENT ■ PHONE ■ FAX ■ BY TIME:

PHONE/FAX No:

QML Fee ■ S.F. ■ B.B. or D.B. ■ VET AFFAIRS No:

……………………………………………………………………/………/………

DOCTOR’S SIGNATURE AND REQUEST DATE

Doct

Copy 1

Copy 2

Copy 3

Hosp/Ward

a. a private patient in a private hospital or approved day hospital facilityb. a private patient in a recognised hospitalc. a public patient in a recognised hospitald. an outpatient of a recognised hospital

Was or will the patient be, at the time of the service or when the specimen is obtained: (✓ appropriate box)

yes no

SELF DETERMINE

PATIENT’S SIGNATURE AND DATEMEDICARE ASSIGNMENT (Section 20A of the Health Insurance Act 1973)I offer to assign my right to benefits to the approved pathology practitioner who will render the requested pathology service(s) and any eligible pathologist determinable service(s) established as necessary by the practitioner. In the alternate, I authorise that APP to submit my unpaid account to Medicare so that Medicare can assess my claim and issue me a cheque payable to the APP for the Medicare Benefit.

SIGNATURE X ................................................................................. X DATE / /

Practitioner’s Use Only ............................................................................................................................................ (Reason patient cannot sign)

Specialist Diagnostic Services Pty Ltd (ABN 84 007 190 043) t/a QML Pathology APA No. 000042. 11 Riverview Place, Metroplex on Gateway, Murarrie Qld 4172 Ph (07) 3121 4444 (24hr services) qml.com.au

PERSON DRAWING BLOODI certify that the blood specimen(s) accompanying this request was drawn from the patient named above. I established the identify of this patient by direct inquiry and/or inspection of wrist band and immediately upon the blood being drawn I labelled the specimen(s).

Signature

....................................................................................................................................

Collect Date Coll. Time Test Codes Branch Ref. No. Lab. No.

Received Date Rec. Time B/C ClinicL UA SB E

Attachments: Yes / No (please circle)If yes, no. of pages:

Description & Collector Containers

MEDICARE CARD NUMBER

Specialist Diagnostic Services Pty Ltd (ABN 84 007 190 043) t/a QML Pathology APA No. 000042. 11 Riverview Place, Metroplex on Gateway, Murarrie Qld 4172. Ph (07) 3121 4444 (24hr services) qml.com.au

PRIVACY NOTE: The information provided will be used to assess any Medicare benefit payable for the services rendered and to facilitate the proper administration of government health programs, and may be used to update enrolment records. Its collection is authorised by provisions of the Health Insurance Act 1973. The information may be disclosed to the Department of Health and Ageing or to a person in the medical practice associated with this claim, or as authorised/required by law.

692250_NTH_Jul17

USE OF PATIENT CONTACT INFORMATION I consent to my contact details (and no clinical information) being used by QML Pathology for marketing communication purposes. PATIENT SIGNATURE X ................................................................................. X DATE / /

Fasting ■

Non Fasting ■

Pregnant ■

Horm Therapy ■LMP ___ / ___ / ___

EDC ___ / ___ / ___

Cervical Screening

Cervix ■

Vagina ■

Self Collect ■

Post Natal ■

IUCD ■

PCB/PMB ■

Abnormal Bleeding ■

Cx Suspicious ■

Previous AIS ■

Radiotherapy ■

Immune deficient ■

PATHOLOGYREQUEST

Cervical Screening Test, Routine

Immunodeficient

WHAT TEST IS REQUIRED? In “Tests Requested” area, enter one of the following:

Cervical Screening Test, Routine ORCervical Co-test, Symptomatic ORCervical Test, follow up of previous abnormal result ORCervical Co-test, Test of Cure ORCervical Co-test, Previous AIS ORCytology Only

ANY OTHER INFORMATION REQUIRED?Other useful clinical information includes:• Immunodeficient• Previous hysterectomy• Self-collected sample• Abnormal uterine bleeding• DES exposure

WHAT ABOUT THE TICKBOXES ON THE REQUEST FORMS?The tickboxes on pathology request forms provide additional useful information for the laboratory. The format of the tickboxes on Pathology request forms can vary, depending on pathology provider, version of form or independent GP practice management software. Please continue to complete all relevant tickboxes.

If you use independent software to electronically complete request forms, you may also wish to set up this software to include terminology as described above.

Merkel cell carcinoma (MCC) is a cutaneous neuroendocrine carcinoma that is relatively rare, but potentially aggressive. It is mainly seen in older people, but also occurs in younger individuals who are immunosuppressed. As for other tumours that are related to UV exposure, the highest incidence rates of MCC are found in Australia and New Zealand. Based on data from 1993-2010, the incidence rate in Queensland is the highest in Australia (1.6 per 100,000 population) and at least double that of anywhere else in the world.

MERKEL CELL POLYOMAVIRUS

Up to 80% of cases of MCC in Northern America/Europe are associated with Merkel cell polyomavirus. In Australia, this association is only about 24%.

CLINICAL

MCC usually presents as a painless, rapidly growing red to violaceous nodule in sun-exposed sites. Other sites can be affected in the immunosuppressed. Whilst most patients present with localised disease, 35% present with nodal disease and up to 14% with distant metastasis. Metastasis to regional and distant sites can be rapid and the overall mortality rate is twice that of cutaneous melanoma (33% vs 15%). Even the smallest primary tumour is associated with a 10-20% risk of occult nodal metastasis at the time of diagnosis.

8-12% of cases presents as a nodal metastasis without a known or detectable primary cutaneous tumour. These cases have a better prognosis, likely reflecting the success of the host immune response in destroying the primary tumour. Tumour regression, either spontaneously or following cessation of immunosuppression, is thought to be related to host immune response activation.

As for other neuroendocrine carcinomas, paraneoplastic syndromes such as cerebellar degeneration, Lambert-Eaton myasthenic syndrome and hyponatraemia can also occur in patients with MCC and, in some cases, these may be the presenting symptoms.

DIAGNOSIS AND PATHOLOGY

The diagnosis is made by biopsy. Immunohistochemistry is required for diagnosis and the main differential diagnosis based on morphology includes metastatic small cell carcinoma and lymphoma. Misdiagnosis as basal cell carcinoma is well documented and some tumours can show squamous differentiation as well as features that are suggestive of melanocytic differentiation. Terminal deoxynucleotidyl transferase (TdT) is expressed in a significant number of MCC, which can potentially lead to misdiagnosis as lymphoblastic lymphoma.

Currently, there is no recommended histological grading system and histological subtyping is not reproducible or of prognostic significance. The growth pattern (circumscribed/nodular or infiltrative) and presence of lymphovascular invasion should be recorded. Breslow thickness and tumour – infiltrating lymphocytes should be reported as for melanoma (a brisk response is associated with a better prognosis). Although p63 expression is associated with a more aggressive course and is an important predictor of shorter survival in cases from Europe/North America, this association has not been found in Australian cases. For nodes, information on the size of largest nodal metastasis, extranodal extension and presence of isolated tumour cells are required.

QML PATHOLOGY UPDATES

Merkel Cell Carcinoma: An UpdateDr Patricia Renaut, QML Pathology

H & E

CK20

Synaptophysin

QML PATHOLOGY UPDATES

MANAGEMENT

Following diagnosis, the patient should undergo full clinical examination of skin and regional lymph nodes. Baseline blood tests (full blood count, biochemistry and coagulation) and staging scans should be performed. Although there is increasing evidence that PET-CT offers increased sensitivity over conventional CT and MRI, the use of this for Merkel cell carcinoma does not currently attract Medicare funding. MRI is more sensitive than CT for detecting brain metastases. As false positive radiology results may occur, tissue biopsy confirmation of metastasis is recommended.

SENTINEL LYMPH NODE BIOPSY (SLNB)

For patients with disease that is localised to the skin and without clinical/radiological evidence of metastasis, SLNB is important to complete the staging process. SLNB should also be considered in patients who have clinically palpable, but radiologically negative lymph nodes. It is usually performed at the time of definitive wide local excision. The success rate of identifying the draining sentinel lymph node may be impaired if the patient has already had a wide excision or flap repair as this may disrupt the lymphatic drainage. There are also site-related difficulties in the detection of sentinel lymph nodes in the head and neck. In this location, the draining nodes are often close to the primary tumour and may be obscured by the injected tracer. The risk of surgical complications is also higher due to the proximity of nerves and blood vessels.

When it is not appropriate to perform SLNB due to high surgical risk, ultrasound evaluation with fine needle aspiration biopsy may be a suitable alternative. In patients who are not surgical candidates, SLNB is usually not performed and the nodal basin should be irradiated.

EXCISION AND MARGIN CLEARANCE

The primary tumour should be excised; however, there is no evidence-based consensus recommendation for either surgical or histological margins. Although older studies recommend wide surgical margins of 2-3cm, the current trend is for a narrower surgical margin of 1-2cm regardless of tumour size, followed by adjuvant irradiation of the tumour bed. There is no minimum recommended histological clearance, but positive histological margins should be re-excised. If Mohs surgery is used, the central portion of the tumour should be sent for permanent section analysis.

RADIATION THERAPY (RT)

Most trials have shown that adjuvant RT reduces the risk of recurrence compared to surgery alone, but there is a lack of consensus regarding its use. Whilst some experts do not consider RT to be necessary in stage 1 tumours with histological clear margins, the National Comprehensive

Cancer Network recommends post-operative RT regardless of stage. RT alone of the primary tumour and/or regional nodal basin can be used as the definitive treatment for patients who are unable to tolerate surgery or as palliation in inoperable cases.

LYMPHADENECTOMY

Patients with clinical nodal disease should undergo completion lymphadenectomy (CL). Adjuvant RT of the nodal basin is also recommended if there is extensive disease with extranodal spread. Whilst the current recommendation for positive SLNB is CL and/or RT, it is unclear whether CL provides additional benefit compared to RT alone.

CHEMOTHERAPY (CT)

CT is reserved for metastatic disease. Although MCC is chemosensitive, CT only provides short term benefit and most cases recur within 4 to 15 months. Adjuvant CT is not recommended as it does not provide a clear benefit.

IMMUNOTHERAPY

In March 2017, the drug Avelumab, a programmed death ligand-1 (PD-L1) inhibitor, received FDA approval in the USA for the treatment of metastatic MCC. It activates the immune response by inhibiting PD-L1, high levels of which are found in virus-negative MCC. Clinical trials of other immune modulators are ongoing.

FOLLOW UP

As most recurrences present within 3 years of diagnosis of the primary cutaneous tumour, the suggested follow up interval is every 3-6 months for the first 2 years, reducing to every 6-12 months.

Key points

• MCC is a relatively rare but potentially aggressive tumour

• Overall mortality is twice that for melanoma

• Progression can be rapid and urgent referral is essential

• Sentinel node biopsy may be required for staging

• Radiation therapy is an integral part of the treatment

• Large excisions or flap repair may alter the tumour bed and compromise sentinel node biopsy or radiation therapy

• Avelumab is a PD-L1 inhibitor that has received FDA approval for metastatic MCC

FURTHER INFORMATION

This article has been shortened for the newsletter. A more detailed version of the article is available on the QML Pathology website.

QML PATHOLOGY UPDATES

BACKGROUND

Subclinical hypothyroidism refers to a situation where the serum thyroid stimulating hormone, or TSH, is mildly raised (above the relevant reference interval, but less than 10 mU/L) and the free thyroxine (Free T4, or FT4) is normal. The clinical relevance to pregnancy is that this group of women has been shown to be at increased risk of certain pregnancy complications, particularly early pregnancy loss and premature birth, and particularly if both TSH and thyroid antibodies are high. The risk has been shown to be reduced by L-thyroxine therapy.

There has been considerable controversy surrounding this topic in pregnancy, specifically in the first trimester, for a number of reasons.

The first controversy is whether to universally screen pregnant women in early pregnancy, or to identify and test only high-risk women (such as those with a personal or family history of thyroid disorders, those with a history of thyroid surgery or neck irradiation, autoimmune disorders etc.). Proponents of universal screening point to the fact that thyroid disorders are common and, particularly for the more common hypothyroidism, the availability of a safe and effective therapy (levo-thyroxine, or L-T4 therapy). The 2017 ATA guidelines make no recommendation either way.

The second controversy is what actually defines a “normal” TSH in pregnancy. QML Pathology has developed reference intervals for each of the three trimesters of pregnancy, as recommended in both the 2011 and 2017 guidelines.

Both of these guidelines also make the suggestion of a “universal” upper limit of normal for TSH to be applied where local ranges are unavailable. This appears flawed due to the ongoing differences in TSH results between different test manufacturers. The 2017 guidelines have, however, “relaxed” this suggested upper limit to 4.0 mU/L (from 2.5 in 2011), as evidence has accumulated in the interim. The latest evidence suggests that for premature birth in particular, evidence of risk is seen at TSH above 2.5 mU/L where thyroid antibodies, particularly anti-thyroid peroxidase (TPOAb), are positive and at TSH 5-10 where TPO antibodies are negative.

KEY POINTS

If performed, a TSH should be done preferably about 8-10 weeks. Note, in women with known hypothyroidism on thyroxine, TFTs should be assessed as soon as pregnancy is suspected or confirmed. Note, measurement of Free T4 attracts a Medicare rebate only under certain circumstances and, of most relevance to screening, if the TSH is raised.

Thyroid antibodies (particularly TPOAb) should be performed if TSH >= 2.5 mU/L.

Treatment decisions should be based on TFTs and thyroid antibodies. Target TSH in the lower half of the pregnancy related interval.

Abnormal results should be reviewed 4 weekly until mid-pregnancy and, in general, treatment should be discussed with or monitored by a specialist.

Subclinical Hypothyroidism in Early Pregnancy: An Update based on the 2017 American Thyroid Association (ATA) GuidelinesDr George Marshall, QML Pathology

2017 ATA Guideline Recommendations – taking into account QML Pathology’s pregnancy reference intervals

First trimester TSH (mU/L) R.I.: 0.1-2.8 Free T4 TPOAb Recommendation (Strength of recommendation)

Normal N (if done)t Neg No treatment (Strong)

Normal* N (if done)t POS

4 weekly TSH until mid-pregnancy (Weak) *L-T4 therapy may be considered:� If TSH is high-normal (2.5-2.8)� In the context of recurrent early pregnancy loss

High, but less than 10** N NegL-T4 therapy may be considered (Weak) **Treatment should probably be considered at or above 4.0 mU/L

High, but less than 10 N POS TREAT with L-T4, 4 weekly review (Strong)

High, but less than 10 Low# AnyTREAT with L-T4, 4 weekly review (Strong) #This denotes “overt” hypothyroidism and should be treated

>=10 Any Any TREAT with L-T4, 4 weekly review (Strong)N = normal. Neg = negative. POS = positive. L-T4 = levothyroxine. TPOAb = anti-thyroid peroxidase antibodytNo Medicare rebate applies for free T4 if the TSH is normal, unless specific indications are noted on the request form (known thyroid

disease, suspected pituitary disease, investigation of infertility, psychiatric disturbance, dementia or the patient is on drugs known to interfere with thyroid function).

From the Education Desk - November 2017

QML PATHOLOGY UPDATES

Dr George Marshall is an experienced Chemical Pathologist with a special interest in endocrinology, toxicology and inborn errors of metabolism. Dr Marshall completed his undergraduate medical training in New Zealand, before completing his specialist training in Chemical Pathology in Brisbane. Following specialist appointments in Melbourne and Brisbane, he joined QML Pathology in June 2017. Dr Marshall is available for consultation in all areas of biochemistry, endocrinology and toxicology.

Dr George Marshall MB ChB (Otago), FRCPA

Chemical Pathologist

P: (07) 3121 4444

E: George.Marshall@qml.com.au

PATHOLOGIST PROFILE

2017 and the start of the Triennium has been a very busy time for the Education team, we have travelled far and wide to bring ALM’s, events and audits to the Doctors of Queensland and Northern NSW with an overwhelming positive response.

THE CYTOLOGY PAP SMEARS AUDIT

1st December 2017 we say goodbye and close this audit in line with National Cervical Screening Program’s “The Renewal”. Last uploads of points will be for the end of November 2017 report which will be completed and to you in late December. I would like to thank all participants over the years and hope that the statistical findings, plus HPV & STI component included over the existence of this audit has been beneficial to you.

THE SURGICAL SKIN AUDIT

This year has seen a record number of registrations from many practitioners with many hundreds of doctors qualifying for their Cat 1 points so far this year. As a reminder The Surgical Skin Audit has specialised request forms, please ensure the reverse of the request form is completed to ensure your specimen is included in your count. To order, please use your stores request forms via your local laboratory or via the website.

We have new literature available on Merkel Cell & What’s new in Skin Cancer Staging as well as updated material on Basal & Squamous Cell Carcinoma to view on our website. You will find all publications available on the Surgical Skin Audit page of the website in PDF format for you to either view on screen or download for your reference.

THE DYSGLYCAEMIC AND DIABETES MELLITUS AUDIT

Our new audit released for the 2017 Triennium has seen a record number of registrations with qualifiers gaining their Cat 1 points. As this audit is reflective in nature we request all qualifiers to review their cumulative report and complete the compulsory evaluation. We have received over 900 responses to date all of which have been

immensely pleasing and very complimentary of the audit. Overwhelmingly, the 9 month snapshot of their practice has assisted practitioners to identify those patients who may be at risk of developing Diabetes Mellitus Type 2 and be able to action earlier “as they may have slipped through the net” as well as review their patients glycaemic targets for individuals with Type 1 and Type 2 Diabetes, accounting for factors such as age and co-morbidity. We are also receiving a great deal of ideas and follow up on topics for the next step in this audit, we would like to thank all doctors for their input, kind words and support.

***Please note - If you are registered for this audit please ensure your surgery staff are aware that you will be receiving your two documents – your 3 monthly report and the non-presenting patient report via post/courier. This report carries patient names and other personal details, therefore cannot be emailed.***

A quick refresher is listed below to assist you.

3 monthly reports will show the clinician:

Dysglycaemic states

• Identifies the number of patients with impaired glucose within a 3 month snapshot.

• The table beside will display those patients who have recorded a raised glucose level and have been followed up.

• The non-presenting patients report (sent via hard copy) will be those patients that have been identified with a raised blood glucose which have not presented for any follow up testing at a QML Pathology collection centre.* Follow up of the individual patient is at doctor’s discretion; however, recommendations are for a repeat fasting glucose, HbA1c or GTT.

>>> CONTINUED OVERLEAF

QML PATHOLOGY UPDATES

Diabetes Mellitus

• Monitor patients already diagnosed with Diabetes Type 1 or 2.

• HbA1c results indicating how well your patients are controlling their Diabetes within the defined timeframe

• See exact number of recommended tests in line with the annual cycle of care requested for your patients diagnosed with Diabetes Type 1 or 2, within the defined timeframe.

*Please note - Patient figures and statistics included in the reporting can only reflect those patients who have been referred and presented for testing at QML Pathology.

Gestational Diabetes is excluded from this audit.

EVENTS

QML Pathology Cytology roadshow THE RENEWAL has been providing educational meetings from Cairns to Northern Rivers with events experiencing wait lists for doctors wanting to attend. We have tried to accommodate

where possible and we thank those doctors who have let us know of their inability to attend prior to the event, it helped immensely to accommodate most on the “wait list”. We would also like to thank all Specialists up and down QLD who have been involved for giving up their time and assisting in QML Pathology Education.

In this triennium, we have also held our exclusive invitation only Skin events again which have seen us travel to some beautiful areas on the Sunshine Coast and Gold Coast for these ALM workshops. Please keep a watch out for your personal invitation and respond promptly to avoid disappointment.

For further information on all of our upcoming educational activities please visit our website qml.com.au or contact your local Medical Liaison Officer or the Education team directly via email at education@qml.com

Warm regards and hope to see you soon at our events, The QML Pathology Education team

Changes to Medicare Eligibility for QuantiFERON® Tuberculosis Testing from 1 July 2017

On July 1st Medicare released updated criteria for QuantiFERON testing. If these criteria are not met by patients an out of pocket charge of $60 will apply. Those patients that have been referred from any Tuberculosis Clinics should be covered under section (a) of schedule 69471 under Medicare.

Quantiferon Testing: 69471 – Test of cell-mediated immune response in blood for the detection of latent tuberculosis by interferon gamma release assay (IGRA) in the following people:

(a) a person who has been exposed to a confirmed case of active tuberculosis;(b a person who is infected with human immunodeficiency virus;(c) a person who is to commence, or has commenced, tumour necrosis factor (TNF) inhibitor therapy;(d) a person who is to commence, or has commenced, renal dialysis;(e) a person with silicosis;(f ) a person who is, or is about to become, immunosuppressed because of a disease, or a medical treatment, not mentioned

in paragraphs (a) to (e)

Doctor Noticeboard

Dr Moe Thuzar MBBS, MRCP (UK), FRACP

Dr Thuzar is an Endocrinologist trained in Queensland. She has recently joined a private endocrine practice in Upper Mt Gravatt. She is also a Staff Specialist Endocrinologist at the Princess Alexandra Hospital, and a Senior Lecturer at the School of Medicine, University of Queensland. Dr Thuzar provides patient-centred care in all areas of general endocrine conditions including diabetes, thyroid, parathyroid, osteoporosis, adrenal and pituitary diseases.

P: (07) 3349 0953 / F: (07) 3420 6243 E: endospecialist@optusnet.com.au

Dr Fatima Ashrafi FRCS(Edin) FRCOG (London) FRANZCOG

Dr Ashrafi is a highly qualified Gynaecologist with over 20 years’ experience in obstetrics and gynaecology which has seen her help women across the globe in Bangladesh, Iran, United Kingdom, New Zealand and Australia. Special services: Early pregnancy, pap smears and colposcopy, menstrual disorders, urinary incontinence, vulvar disorders, female sexual dysfunction, contraception, menopause management and Mona Lisa laser therapy for vaginal rejuvenation.

P: (07) 3193 0873 / F: (07) 3036 6682 W: www.avicennahealth.net.au

The pathologists and staff at QML Pathology wish you a joyous festive season, filled with peace and good health. QML Pathology is proud to continue its support of Heart of Australia again in 2017.

Heart of Australia is breaking the grip of distance that denies rural and remote-area Australians access to specialist services when and where they are needed most.

Via its customized road-train – a specialist medical clinic on wheels - Heart of Australia delivers fortnightly specialist medical investigation and treatment clinics to regional, rural and remote area communities across Queensland, including Dalby, Goondiwindi, Stanthorpe, St George, Charleville, Roma, Emerald, Barcaldine, Longreach, Hughenden, Winton, Charters Towers and Moranbah.

The Heart of Australia road train has completed over 6,000 patient consults and has travelled more than 250,000 kilometres in just 3 years.

For more information on Heart of Australia please visit heartofaustralia.com

QML Pathology Collection Centre Festive Season Opening HoursCollection centre opening hours over the holiday period will be updated on our online Collection Centre Search.

Locate collection centres within a desired region from suburb or postcode information.Obtain collection centre operational hours and contact information.Receive up-to-date public holiday or temporary closure times.Search for collection centres who perform specific tests.Find licence details and general centre features (e.g. on-site parking, on-site bathroom facilities, and test payment options).

To check hours please visit qml.com.au/CollectionCentres.aspx

Warfarin Care Clinic Holiday Closures QML Pathology wishes to advise that the Warfarin Care Clinic will not be accepting any NEW REGISTRATIONS from 5pm on Wednesday 13th December, 2017.

This service will re-open from 8am Tuesday 2nd January, 2018.

Patients who are currently monitored by QML Pathology and are being discharged from hospital will still be accepted during this time. However, patients discharged from hospital who are prescribed Clexane (LMWH) must remain under the care of the hospital, or be referred to their doctor until LMWH is ceased and INR returns to therapeutic range.

CLINICAL DATA

This newsletter has been prepared and published by QML Pathology for the information of referring doctors. Although every effort has been made to ensure that the newsletter is free from error or omission, readers are advised that the newsletter is not a substitute for detailed professional advice. © Copyright 2016.

Infectious Diseases ReportGEOGRAPHIC DISTRIBUTION - SEP 2017

ORGANISMRegions (as per key below) TOTAL

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 SEP AUG JULAdenovirus (not typed) 2 26 13 2 31 22 4 70 13 10 5 4 202 198 123

Adenovirus (typing pending) 2 1 3 1 1 5 3 1 3 20 32 16

Barmah Forest virus 1 1 2 2 9

Bordetella pertussis 4 24 12 6 1 16 12 9 30 18 6 2 15 155 184 162

Brucella species 1 1 2 3 2

Campylobacter jejuni 5 5

Chlamydia pneumoniae

Chlamydia trachomatis, not typed 71 99 35 27 6 146 2 57 30 192 71 14 43 28 821 911 936

Coxiella burnetii 1 1 3 1 2 4 12 12 9

Cryptococcus species 3 3

Cytomegalovirus (CMV) 3 3 1 4 5 1 10 6 1 1 35 48 43

Entamoeba histolytica

Enterovirus - not typed 1

Epstein-Barr virus (EBV) 6 16 8 1 37 6 8 43 21 7 7 8 168 170 117

Flavivirus unspecified 1 1 2 4 1 1 10 2 5

Hepatitis A virus 1 1 1 3 3 2

Hepatitis B virus 9 8 8 1 22 6 1 79 1 3 1 3 142 155 136

Hepatitis C virus 22 43 26 5 1 40 34 5 97 23 20 12 23 351 407 361

Hepatitis D virus 1

Hepatitis E virus 1 1 2

Herpes simplex Type 1 24 54 31 7 2 1 75 42 20 129 56 11 19 15 486 526 493

Herpes simplex Type 2 20 45 8 1 1 32 9 9 57 22 8 5 3 220 222 210

Herpes simplex virus - not typed

HIV-1 3 1 2 6 26 14

HTLV-1 2 1

Human Metapneumovirus 5 72 33 6 1 37 61 8 96 34 17 3 24 397 341 189

Influenza A virus 84 423 246 41 6 4 387 3 399 232 852 331 175 104 211 3498 5938 1512

Influenza B virus 58 336 283 36 1 2 283 1 272 47 641 302 282 99 60 2703 2614 574

Legionella pneumophila (all serogroups) 2 2 1

Legionella species 1 1

Leptospira species 3 3 3 6

Measles virus

Mumps virus 1 1 1 3 1

Mycoplasma pneumoniae 23 6 3 1 18 14 11 37 8 6 6 9 142 125 133

Neisseria gonorrhoeae 3 7 5 2 20 1 6 1 26 12 2 1 1 87 107 96

Parainfluenza virus 13 75 36 7 2 43 50 18 141 63 13 14 11 486 445 202

Parvovirus 1 3 6 6 5 2 8 4 3 38 23 14

Pneumocystis carinii 1 1 2 4

Respiratory Syncytial virus 2 37 12 3 31 31 18 28 31 12 10 14 229 387 406

Rhinovirus (all types) 19 67 31 7 48 49 22 116 48 16 18 14 455 556 477

Rickettsia - Spotted Fever Group 2 1 1 4 6 4

Ross River virus 3 5 1 4 2 4 5 10 5 2 3 5 49 47 82

Rubella virus 1 1 1

Salmonella paratyphi A 1 1

Salmonella paratyphi B

Salmonella typhi

Streptococcus Group A 9 7 5 4 12 108 18 5 21 11 6 1 6 213 242 181

Toxoplasma gondii 2 1 2 1 4 1 1 12 15 18

Treponema pallidum 34 11 5 2 15 69 7 12 5 56 8 5 36 4 269 322 240

Trichomonas vaginalis 15 1 6 3 3 1 4 1 7 1 4 46 44 35

Varicella Zoster virus 7 42 30 7 1 61 35 5 116 35 9 14 6 368 350 340

Yersinia enterocolitica

TOTAL 415 1433 854 172 44 7 1436 124 1158 470 2886 1130 633 421 466 11649 14479 7156

FURTHER HISTORICAL CLINICAL DATA CAN BE OBTAINED BY CONTACTING MARKETING ON INFO@QML.COM.AU.

REGIONS:1 Cairns2 Gold Coast/Tweed3 Ipswich

4 Mackay5 Mount Isa6 New England7 North Brisbane

8 Northern Territory9 Redcliffe10 Rockhampton11 South Brisbane

12 Sunshine Coast13 Toowoomba14 Townsville15 Wide Bay/Burnett

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