How do we help pathologists find pathology? Dan C. Martin, MD Professor, Department of Obstetrics and Gynecology Divisional Director of Minimally Invasive Surgery Divisional Director Reproductive Endocrinology Director Minimally Invasive Surgery Fellowship Faculty Senator, University of Tennessee Health Science Center Memphis, Tennessee.
March 27-29, 2014 Atlanta, Georgia
Learning Objectives At the end of this presentation, participants should be able to: • Be aware of STARD criteria • Understand the use of select STARD criteria in clinical care • Clarify a signal-noise ratio • Review available staining techniques. • Communicate better with pathologists
Conflict of Interest • None
Confirmation at a Research Level STARD Sta ndards for R eporting of D iagnostic Accuracy Bossuyt PM, Reitsma JB, Bruns DE, et al. Towards Complete and Accurate Reporting of Studies of Diagnostic Accuracy: The STARD Initiative Clinical Chemistry 49:1, 1–6 (2003)
Confirmation at a Research Level • The protocol needs to be a fixed in order to be compatible with STARD. The protocol in yellow below may not be compatible with STARD • Surgeon Experience Clarified • No Expectation of Appearance vs. Specified Appearances “Absence of Normal Appearance” vs. “Appearance of Endometriosis” • Biopsy Techniques (biopsy forceps, nmicro-scissors, trim large specimens, micro-point monopolar electrosurgery knife, 5000+ w/cm 2 CO 2 LASER) • Additional punctures and equipment for additional control • Adequate Number of Biopsies • Signal to Noise Ratio (trim specimens) • Tagging the Specimen Location • Marking the Specimen Side • Notations on Pathology Request (i.e. 1 mm lesion, 19+ from 1986, other?) • Uniform Specimen Size in Container • Cell Block • Transferring the Specimen to Container and then to Cassette • Processing by the Surgeon • Communications with the Cutters • Communications with the Pathologist • Re-cutting Specimens • Histologic Criteria (Batt 1989) • Infectious disease cultures, NNA, DDA, titers, etc. in pain studies • Routine or selective use of iron stains (hemosiderin, other iron forms and steroid pigment) • Routine or selective use of trichrome staining for collagen and muscle • Require a Histology Description Compatible with Surgical Findings. A 1 mm lesion requires histology compatible with a 1 mm lesion. • Reviewing Slides .
Confirmation at a Combined Research / Clinical Level • No Expectation of Appearance or that any appearance is endometriosis • Biopsy Techniques (biopsy forceps, scissors, knife) • Adequate Number of Biopsies • Signal to Noise Ratio (trim specimens) • Tagging the Specimen Location • Notations on Pathology Request (i.e. 1 mm lesion, 19+ from 1986, other?) • Uniform Specimen Size in Container • Cell Block • Transferring the Specimen to Container and then to Cassette • Communications with the Cutters and Pathologists • Selective use of iron stains (hemosiderin, other iron forms and steroid pigment) • Selective use of trichrome staining for collagen and muscle • Reviewing Slides. • Require a Histology Description Compatible with Surgical Findings. A 1 mm lesion requires histology compatible with a 1 mm lesion.
Confirmation at a Clinical Level • No expectation that any appearance is endometriosis • Tag small lesions on large specimens • Signal to noise ratio • Notations on pathology request (i.e. 1 mm lesion) • Selective use of iron stains for iron forms • A 1 mm lesion requires histology compatible with a 1 mm lesion.
What do we know?
Non-Specific Lesions These are non-specific lesions unless pathology is specific.
Non-Specific Lesions Small clear and small white lesions - Endometriosis - Endosalpingiosis - Psammoma Bodies - Lymphoid Aggregates - Non-specific Inclusions - Mesothelial Proliferation If on a Fallopian tube, add - Walthard Rest With clusters, add - Low Malignant Potential Tumor If there are solid nodules, add - Metastatic Cancer
Grades of Certainty • Grade 1: Possible residua of resorbed endometriosis, i.e., hemosiderin, calcium, nerve, blood vessels and smooth muscle. • Grade 2: Consistent with endometriosis, i.e., hemosiderin, characteristic glands, OR stroma. • Grade 3: Definite endometriosis, i.e., characteristic glands AND stroma with hemosiderin. • Grade 4: Grade III with structures conveying and organoid pattern, i.e., glandular-stromal layer overlying well developed smooth muscle layer Batt RE et.al. A case-series -- peritoneal pockets and endometriosis: rudimentary duplications of the Müllerian system. Adolesc Pediatr Gynecol. 1989: 2:47-56
What is Classical? • Obliterated Pouch of Douglas • Powder Burn • Clear, Red, and/or White?
Classical 1860 – 1920 Batt Grades 3 and 4 Futh 1903 Lockyer 1918
Classical 1960 - 2000 Batt Grade 2, 3, or 4
Iron Stain Iron staining of the peritoneum may aid in clarifying the brown appearance of the peritoneum.
Classical 2005 Batt Grade 1 Endometriosis, Precursor or Facilitator Batt Grade 1: possible residua of resorbed endometriosis, i.e., hemosiderin, calcium, nerve, blood vessels, and smooth muscle. Batt, et al. 1989; Marsh and Laufer 2005: Cabana et al. 2010 ===================== Broad Ligament Inflammatory Induction Facilitator for Retrograde Flow Left Coincidence Another “Watch this space” story Ovary Uterosacral Ligament
Look-a-Like Lesions Uterus
Signal – Noise Ratio Tag large lesions.
Signal – Noise Ratio Uterus 2.5 cm Utero-sacral ligament 3 mm 2 mm 1 mm 0.5 mm Ovary
Signal – Noise Ratio 10 mm 1 mm
Signal – Noise Ratio • 1 cm specimen with 1 mm lesion – Linear is 1 mm signal with 9 mm noise (1:9) – Volumetric is 1 mm 2 in 78.5 mm 2 ( π r 2 ) (1:77.5) • 2 mm specimen with 1 mm lesion – Linear is 1 mm signal with 1 mm noise (1:2) – Volumetric is 1 mm 2 in 3.14 mm 2 ( π r 2 ) (1:2.14)
Signal – Noise Ratio 2 mm 1 mm
Diagnosis and Confirmation • Diagnosis dark lesions using white light – No confirmation Infertility. Marcoux, 1997 • Diagnosis using white light – No confirmation Chronic pelvic pain. Ling, 1999 • Diagnosis using white light vs. 5-ALA induced fluorescence Confirmation by histology Comparison of illumination. Buchweitz, 2004 • Diagnosis using white light - Confirmation by histology Chronic pelvic pain. Jenkins, 2008 • Diagnosed at laparoscopy - No confirmation Gene polymorphisms . Sundqvist, 2010 • Endometriosis was self-reported - No confirmation Gene polymorphisms . Near, 2010
Positivity – Single Study 100 90 ● 80 Mettler 2003 Percent Positive ● Pardanini 1998 70 ● Pardanini 1998 60 50 ● ● Walters 2001 40 Pardanini 1998 30 20 10 100 200 300 400 500 Cases
Confirmation at a Research Level 99% in last 69 of 495 cases over 60 months (8.2 per month by one physician) Year 1982 1983 1984 1985 1986.1 1986.2 Cumulative Number 97 188 279 376 426 495 of Patients by One Gyn Positive for Endo 91% 93% 96% 99% 62% 50% when Excised Martin 1987, Stripling 1988, Martin 1990 42% to 76% range by 3 physicians doing 11 to 22 cases. Pardanani, Barbieri 1998 (Harvard, Boston) 45% PPV in 44 cases over 20 months (2.2 per month by ?? physicians) Walter, Magrina, et al. 2001 (Mayo Clinic, Phoenix, Arizona) 61% of lesions in first 46 cases over 34 months (1.4 per month by ?? physicians) 68% of lesions in next 56 cases over 36 months (1.6 per month by ?? physicians) Stratton 2003, Stegmann 2005 (NIH Bethesda clinical group) 87% in research conditions, 56% in clinical use. Buchweitz 2003, Luebeck, Germany 88% in 72 clinical cases over 7 months (10.3 cases per month by one physician) Webb, Martin et al. in preparation
Positivity – Time Intervals ● 100 ● ● 90 Martin 1987, Stripling 1988, Martin 1989, Martin 1990 ● 80 Percent Positive Dulumba 2012 70 ● ● ● 60 ● Stratton 2002, Stegmann 2008 ● 50 40 30 20 10 100 200 300 400 500 Cumulative Cases
Positivity – Research v Clinical Stripling 1988, Martin 1990 ● 100 Webb, Martin 2005 90 ● ● 80 Buchweitz 2003 70 ● 60 Percent Positive Buchweitz, 2003 50 40 30 20 10 Research Clinical
Psammoma Bodies, Ovary, Endosalpingiosis, LMPT and Metastatic Cancer Psammoma Bodies Remnant Ovary Endosalpingiosis Bladder Uterus Low Malignant Metastatic Breast Cancer Potential Tumor
Conclusions • Biopsy can be useful. • Cancer can be missed. • Therapeutic research needs histology as a criteria.
SLIDES FOR Q&A
Marsh 2005
Endometriosis After Inflammation
Endometriosis After Inflammation • Induction • Damage predisposing to implantation • Coincidence
Marsh 760
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