Using the “Tumor KGS Index” and “KGS Prognostic Chart” in Clinical Oncology
The true prognostic value and practicality of a tumor’s grading can only be fulfilled with the numerical data related to the tumor’s cells, the leading players of oncogenesis, which tell us all for measurement, assessment and evaluation and grading, as well as its metastatic scale which is the stern determinant of the tumor’s ultimacy. So that, I incorporate the parametric data scores of the KGS Index into the grading part of the KGS which thereby functions as a complete, uniquely effective, practical and helpful grading system.
In the KGS’s part of scoring parameters, there is no particular grading or sub-grading. While the grading part, in itself, is an essential independent constituent of the KGS paradigm, the scoring part, also independent in itself, is methodologically integrated into it making the KGS a unique wholesome norm and tool of diagnostic and prognostic guidance.
[Full details may be viewed in the main article which is due shortly]
In a sample case of Grade VIB Pancreatic Ductal Adenocarcinoma detailed below, we use the KGS index and KGS Prognostic Chart (KGS Chart) with the Diagnostic KGS Profile and Prognostic KGS Ranging:
SAMPLE CASE : Grade VIIB Pancreatic Ductal Adenocarcinoma
In this example, we see an inoperable (due to location) Grade VIB Pancreatic Ductal Adenocarcinoma with duodenal obstruction. Having no metastasis, the 45 year-old male patient receives palliative surgical and endoscopic treatment along with oncotherapy which includes both chemotherapy and radiotherapy. Although inoperable by protocol, the tumor is partially resectable and allows partial palliative resection and laparoscopic biopsies. The ease in the palliative surgical and endoscopic treatment, the permissiveness in diagnostic follow-up, the absence of metastasis, and the relatively young age of the patient collectively provides the clinical team with encouragement to conduct an intensive oncotherapy which brings a progressively dramatic result.
Below are the Final “KGS Pathology Report”, “KGS Diagnostic Profile”, “KGS Prognostic Profile” and “KGS Prognostic Chart” (“KGS Chart”) of the patient.
1. The “KGS Pathology Report” & “KGS Diagnostic Profile”
A. First KGS Report:
Biopsy: Pancreatic Tumor
Date of Collection: 07.02.2013
Date of Report: 16.02.2013
Diagnosis: Pancreatic Ductal Adenocarcinoma
KGS Grade: VIB
Microscopic Description: With a sizeably, but not extensively, infiltrative growth pattern, the moderately differentiated Grade VIB cells within dominating poorly-differentiated neoplastic glandular mucoepidermoid and pleomorphic structures; slightGrade VIIA tendency with a few sporadically seen clusters of Grade VIIA cells which quantitatively are not enough to qualify the tissue as Grade VIIA; in 10 HPFs, 14Grade VIBm (mitotic) cells (14/10PHF) and 5 Grade VIBn (necrotic) cells (5/10HPF); sporadic small Grade VC and Grade VIA areas.
Original KGS Grade: VIB / VIIA
Overall KGS Grade: VIB
KGS Index: 38.72
KGS Prognostic Range: E
Pathologic Diagnosis: “Grade VIB Pancreatic Ductal Adenocarcinoma”
B. Final KGS Report:
Biopsy: Post-therapy Pancreatic Tumor
Date of Collection: 07.08.2014
Date of Report: 15.08.2014
Diagnosis: Regressed Pancreatic Ductal Adenocarcinoma
KGS Grade: VIR (Regressed Grade VI Tumor)
Microscopic Description: The Grade VIB tumor’s substantial regression to Grade VIR0 with a zero PTR (Post-Therapy Regression) score (KGS 0); dominating necrosis and fibrosis; no visible/viable tumor cells; rare dying Grade VIB cells among overwhelming groups of Grade VIRn (necrotic) cells; no Grade VIBm (mitotic) cells in 10 HPFs (0/10PHF); 7 Grade VIBo (apoptotic) cells in 10 HPFs (7/10PHF).
Original KGS Grade: VIB
Overall KGS Grade: VIR (VIR0)
KGS Index: -0.50
First KGS Index: 38.72 [Report Date: 16.02.2013]
PTR (Post-Therapy Regression) Score: 0 (KGS 0)
KGS Prognostic Range: N
Pathologic Diagnosis: “Regressed Grade VIB Pancreatic Ductal Adenocarcinoma”
2. The “KGS Prognostic Profile”
KGS
Grade….VIB……VIB…..VIB……VIR5….VIR4…VIR3…..VIR2….VIR1…VIR0….I..
KGS
Index…38.72…34.25…30.17….21.15….16.39….11.85…..9.40…..4.55….1.10…-0.50
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Date 16.02.13……I………..I…………I………..I………..I………..I………..I………I..15.08.14
..DATE………………….KGS INDEX………….KGS GRADE
16.02.13……………………… 38.72 ……………………. VIB …….
15.04.13……………………… 34.25 ……………………. VIB …….
21.06.13……………………… 30.17 ……………………. VIB …….
14.08.13……………………… 21.15 …………………… VIR5 …….
25.10.13……………………… 16.39 …………………… VIR4 …….
19.12.13……………………… 11.85 …………………… VIR3 ……
18.02.14………………………. 9.40 ……………………. VIR2 ……
21.04.14………………………. 4.55 ……………………. VIR1 ……
11.06.14………………………. 1.10 ……………………. VIR0 ……
15.08.14……………………… -0.50 ………………………. I ……….
KGS Prognostic Profile
In these two tables, the parametric “KGS Prognostic Profile” of the above case is shown in two forms as seen in pathology reports and clinical files. In this regressing Grade VIIB Pancreatic Ductal Adenocarcinoma, we see a dramatically changing KGS Indexover a period of 18-month oncotherapy at the end of which we see a replacing normal (Grade I) pancreatic tissue.
3. “KGS Prognostic Chart” (“KGS Chart”)
….VIB……VIB…..VIB….VIR5…VIR4….VIR3….VIR2…VIR1…VIR0…..I……
U……………………………………………………………………………………………………………
…..38.72………………………………………………………………………………………………….
E…………..34.25………………………………………………………………………………………..
……………………….30.17……………………………………………………………………………..
H………………………………..21.15………………………………………………………………….
……………………………………………..18.39……………………………………………………….
M………………………………………………………11.85…………………………………………….
……………………………………………………………………..7.90…………………………………
L………………………………………………………………………………4.55………………………
……………………………………………………………………………………………1.10……………
N………………………………………………………………………………………………….-0.50….
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16.02.13……I………..I……….I……….I………..I………….I…………I………..I….15.08.14
Figure. 1. The “KGS Prognostic Chart” (KGS Chart) of the patient: Displaying the “Prognostic KGS Ranges” together with a gradually decreasing “KGS Index” by dates, this standard KGS Chart shows the prognostic profile of an inoperable non-metastatic Pancreatic Ductal Carcinoma during a successful chemotherapy and radiotherapy period through which the Grade VIB tumor dramatically regresses being eventually replaced by a normal (Grade I) tissue.
Prognostic KGS Ranges: N=Normal, L=Low, M=Medium, H=High, E=Extreme, U=Ultimate. KGS Grades: VIB=Neoplastic; VIR5, VIR4, VIR, VIR2, VIR1 and VIR0=Regressive (Post-therapy regression); I=Normal Tissue. (The dates of the KGS pathology reports are shown below the base line)
KARINDAS GRADES in KGS RANGES
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Grade 00-0 Inert Range
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00 Necrosis (Ordinary)
0 Atrophy
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Grade I-III Physiologic Range
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I Normality
II Hypertrophy
III Hyperplasia
IIIA Low-grade (Ordinary) Hyperplasia
IIIB High-grade (Atypical) Hyperplasia
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Grade IV-V Preneoplastic Range
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IV Metaplasia
IVA Low-grade Metaplasia
IVB High-grade Metaplasia
V Dysplasia
VA Low-grade Dysplasia
VB Moderate Dysplasia
VC High-grade Dysplasia (Carcinoma In Situ)
VR Regressive Dysplasia
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Grade VI-VII Neoplastic Range
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VI Neoplasia
VIA Well-differentiated
VIB Moderately-differentiated
VIR Regressive
VII Anaplasia
VIIA Poorly-differentiated
VIIB Undifferentiated
VIIR Regressive
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Table 2: The “Karindas Grades” in the “KGS Solid Tissue Ranges”. The capital letters A, B and C symbolize the sub-grades. The “R” symbolizes the “Regressive” state of a tumor which is either “regressing” or “regressed”.
TUMOR NECROSIS IN THE KGS GRADING
Necrosis has an important place in Grade V, Grade VI and Grade VII solid tumors in which a necrotic tissue may appear in two different forms in two different phases of oncogenesis:
- Anaplastic Tumor Necrosis (High Necrosis): In the tissues of advanced anaplasia in high-grade (VIB, VIIA and VIIB) tumors, necrosis frequently emerges as the ultimate characteristic of anaplastic maturement. In the KGS Grading, I entitle the tissue of anaplastic necrosis ”High Necrotic Tissue” (i.e.Grade VIBnecrotic tissue, Grade VIIA necrotic tissue, etc.), and I call the tumor cells it contains “High Necrotic Tumor Cells” grading them as Grade VIBn, GradeVIIAn and Grade VIIBn cells.
- Regressive Tumor Necrosis (Low Necrosis): In “Grade V”, “Grade VI” and “Grade VII” regressive tumors (Grade VR, Grade VIR and Grade VIIR), necrosis may happen either as a result of a successful oncotherapy, or spontaneously. In the KGS Grading, I entitle the necrotic tissue of a regressing or regressed tumor ”Low Necrotic Tissue” (i.e. Grade VR necrotic tissue, Grade VIR necrotic tissue, Grade VIIR necrotic tissue; in more specifically profiled and recorded/reported cases, as Grade VCR, Grade VIAR, Grade VIBR, Grade VIIAR and Grade VIIBR necrotic tissues) and I call the tumor cells it contains “Low Necrotic Tumor Cells” and I grade them as Grade VRn, Grade VIRnand Grade VIIRn cells and the more specific ones as Grade VCRn, Grade VIARn, Grade VIBRn, Grade VIIARn and GradeVIIBRn cells. With the addition of tumors’ PTR (“post-therapy regression”) grading to the KGS grading (e.g. VIIR1: KGS1, VIR5: KGS5, etc.), KGS pathology reports provide much more comprehensive information.
The KGS’s PTR (Post-Therapy Regression) GRADING
__________________________________________________PTR Score: 0 (KGS 0)
KGS Range: VIR0-VIIR0
PTR Criteria: Fully credible neoplastic regression. No trace of residual tumor, no viable tumor cells _______________________________________________________PTR Score: 1(KGS 1)
KGS Range: VIR1-VIIR1
PTR Criteria: Substantial neoplastic regression. Rare (<5%) residual tumor cells
_______________________________________________________PTR Score: 2(KGS 2)
KGS Range: VIR2-VIIR2
PTR Criteria: Significant neoplastic regression. 5-15% residual tumor cells
_______________________________________________________PTR Score: 3(KGS 3)
KGS Range: VIR3-VIIR3
PTR Criteria: Considerable neoplastic regression. 15-35% residual tumor cells
_______________________________________________________PTR Score: 4(KGS 4)
KGS Range: VIR4-VIIR4
PTR Criteria: Limited neoplastic regression. 35-50% residual tumor cells
_______________________________________________________PTR Score: 5(KGS 5)
KGS Range: VIR5-VIIR5
PTR Criteria: Insignificant neoplastic regression. >50% residual tumor cells
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Table 4: KGS-PTR Grading. The KGS’s PTR Grading, a five-tier-scale system, is based on the existing tumor cells’ proportional value in relation to the proportions of necrosis and fibrosis in regressing solid tumors. In pathologic examination reports, tumors’ PTR scores, which are designated as KGS 0, KGS 1, KGS 2, KGS 3, KGS 4, and KGS 5, also indicate the five levels of the grading where the corresponding KGS ranges take place synchronously (e.g. KGS 3 : VIR3-VIIR3)
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Prognostic KGS Ranges
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KGS Index: <1
Prognostic KGS Range: Normal (N)
NORMAL RANGE: This is the range where a totally normal tissue and cells are seen. Examples: 1. A normal tissue with no status or history of neoplastic activity, 2. Fully regressed neoplastic tissue.
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KGS Index: 1-7
Prognostic KGS Range: Low (L)
LOW RANGE: The range of tumoral activity with no considerable neoplastic weight. Examples: 1. Grade III-IV tumors, 2. Almost fully regressed neoplastic tissue.
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KGS Index: 8-18
Prognostic KGS Range: Medium (M)
MEDIUM RANGE: This is the range of emerging neoplastic activity, with considerable neoplastic potential and significance. Examples: 1. Grade VB-VC tumors, 2. Fairly regressed neoplastic tissue.
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KGS Index: 19-29
Prognostic KGS Range: High (H)
HIGH RANGE: The high range is the range of established neoplasia where a qualified malignant tumor tissue takes place with all the features of neoplasia: Fully developed cancer (e.g. Grade VIA-VIB tumors).
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KGS Index: 30-40
Prognostic KGS Range: Extreme (E)
EXTREME RANGE: This is the range of neoplasia where tumors with full neoplastic features and complications, including necrosis (high necrosis) and metastasis, take place: Full-blown cancer (e.g. Grade VIB-VIIA tumors).
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KGS Index: >40
Prognostic KGS Range: Ultimate (U)
ULTIMATE RANGE: The range of the most advanced malignancy with highly malignant anaplastic cells with maximum mitotic, necrotic and metastatic activity: Full-scale anaplasia (e.g. Grade VIIA-VIIB tumors).
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Table 5: The KGS Prognostic Ranges. The prognostic KGS ranges, highly important and crucial to use in the prognostic follow-up in clinical oncology, are used for both malignant and benign tumors. Range levels are determined by the ranges of the “KGS Index” whose variable limits of numerical values directly make up the levels. The “Normal” range level with the KGS Index of “<1” covers normal tissues and regressive tumors that have fully regressed to normality.
The KGS Grading redefines the Pathology Laboratory as the prime station on all fronts of Oncology and the Pathologist as the “Anchor”, and it crucially gives the clinician freedom of movement, and invaluable tools and unprecedented capacity for patient management.
Copyright © 2010-2016 M. M. Karindas, MD
