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Year : 2014 | Volume : 2 | Issue : 2 | Page : 116 - 118  


Case Reports
Gastrointestinal Stromal Tumors (GISTs) – IHC study and correlation of CD-117 and PDGFR-α staining intensity with histomorphological features –A Study of 8 cases

Krishna L1, Rajani V2, Rajeswari R3, Vijaya Bhaskar R4, Sreeramulu Naidu R5

1Professor, Gandhi Medical College, Secundarabad

2 & 3Assistant Professor, 4Associate Professor, 5Principal (Retd) Rangaraya Medical College, Kakinada

Abstract:

Gastrointestinal Stromal Tumors (GISTs) are rare and constitute only 1% of all malignant tumors of the GI Tract but are the most common mesenchymal neoplasm of the GI tract. GISTS are typically defined by the expression of C-KIT (CD-117) in the tumor cells.

Here we report a total number of 8 cases of GISTs studied by Immuno histochemical markers. Panel of IHC markers used are CD-117, PDGFR-α,S-100, Desmin, CD-34, SMA and Epithelial Keratins. CD-117 and PDGFR-α staining intensity correlated with histomorphological features. Risk of progressive disease assessed based on histomorphological features and location of the tumor.

Key Words: GISTs, IHC, Histomorphology, Prognosis

Corresponding Author: Dr.L.Krishna, Profesor of pathology, Gandhi Medical College, Secunderabad, 500 003. Email: lanka.krishna1@gmail.com

 

Introduction:

GISTs are rare tumors but most common mesenchymal neoplasms of the gastrointestinal tract. GISTs can involve the stomach, small intestine, and other portions of the digestive tract, omentum, mesentery, retroperitoneum and other sites such as pleura. [1, 2] GISTs are defined as cellular, spindle, epithelioid or occasionally pleomorphic mesenchymal tumors that express the KIT protein (CD-117) in the tumor cell as detected by the Immunohistochemistry (IHC). KIT is a tyrosine kinase receptor normally expressed by the interstitial cells of cajal, mast cells and germ cells. [1, 2] This KIT mutation is usually at exon 11, rarely at exons 9 and 13. [3] It results in a ligand independent activation of the receptor which in turn leads to its detection at the IHC level. [4] This has provided a very useful tool for the confirmation of the diagnosis of GIST tumor in the sense that such a diagnosis should be questioned when faced with a CD 117 negative tumor except in the case of GISTs of children.

Most GISTs occur in adults but they have also been reported in children and neonates. [5]

Case Report:

A total number of 8 cases of GISTs have been studied with anatomical location, histo morphological features, immune histochemicl profile and Risk of progressive disease assessed. All tumors are negative for epithelial keratins. They are represented in table no 1.

All tumors are grossly grey white with smooth and vaguely nodular appearance of the surface. Cut section all tumors grey white without necrosis or hemorrhage.

Table no 1:

Case no

Anatomical location

Size in cm

Mitotic count/hpf

IHC Positive

IHC Negative

Risk for progressive disease (%)

1

Gastric GIST

8

5/50

S -100

CD-117, PDGFR-α,Desmin, CD-34 and SMA

 

Low(3.6)

2

Gastric GIST

9

8/50

S-100 and SMA

CD-117, PDGFR-α, Desmin and CD-34.

 

High(55 )

3

Gastric GIST

14

12/50

CD-117(strong), PDGFR-α(strong), CD-34,

S-100, Desmin and SMA

 

High(86 )

 

4

Small intestine GIST

6

15/50

CD-117(strong), PDGFR-α (intermediate), CD-34 and SMA

S-100 and Desmin

 

High(85 )

5

Small intestine GIST

11

5/50

CD-117(strong), and SMA

PDGFR-α,S-100, Desmin and CD-34

 

High( 55)

6

Rectum GIST

6

19/50

CD-117(intermediate),, PDGFR-α(intermediate),

S-100 and SMA

Desmin and CD-34

 

Insuff.data

 

7

Mesenteric GIST

10

8/50

CD-117(intermediate) and SMA

PDGFR-α,S-100, Desmin and CD-34

 

High(90 )

8

Mesenteric GIST

13

19/50

PDGFR-α(strong),S-100 and CD-34

CD-117, Desmin and SMA

 

High( 85)

 

Out of eight cases, one of the Gastric GISTs showed the maximum size of 14 cm.

CD117 and PDGFR-α were strongly positive in epithelioid variant of GIST.

One case of CD-117 negative mesenteric GIST strongly positive for PDGFR-α.

Two cases of Gastric GISTs of spindle cell morphology were negative for both CD-117 and PDGFR-α.

Reciprocal expression of CD-34 and SMA is noted in 75% of tumors.

Discussion:

In the present case study CD 117 negative mesenteric GIST showing features of mixed spindle and epithelioid cell morphology is strongly positive for PDGFR-α.

Most CD-117 negative tumors have mutations of the PDGFR-α gene instead of the C-KIT gene. These tumors tend to be myxoid and epithelioid.

Two cases of Gastric GISTs were negative for CD-117 and PDGFR-α

The rare tumors having all the morphological and other phenotypic features of GIST which do not stain for CD-117 should still be diagnosed as GISTs. [6]

Additional immunomarkers for GISTs are DOG1. [7]and CD-171 a cell adhesion molecule also known as L1. [8]

Miettinen.M.et al reported CD-34: SMA reciprocal expression in 75% of the tumors.

The combination of tumor size and mitotic activity and in addition the anatomic location of the tumor provides the most comprehensive information to divide these tumors into risk categories. [9]

Conclusion:

GISTS are uncommon tumors. The GISTs are morphologically and immunophenotypically different tumors. IHC marker CD-117 alone is insufficient for the diagnosis of GISTs. The reciprocal expression of SMA and CD-34 is seen in 75% of GISTs.

References:

  1. Long KB, Butrynski JE, Blank SD, Ebrahim KS, Dressel DM, Heinrich MC, Corless CL, Hornick JL: Primary extragastrointestinal stromal tumor of the pleura: report of a unique case with genetic confirmation. Am J Surgpathol 2010; 34:907-912.
  2. Reith JD, Goldblum JR, Lyles RH, Weiss SW: Extragastrointestinal (soft tissue) stromal tumors: an analysis of 48 cases with emphasis on histologic predictors of outcome. Mod pathol 2000; 13:577-585.
  3. Heinrich MC, Rubin BP, Lonley B, Fletcher JA: Biology and Genetic aspects of gastrointestinal stromal tumors: Kit activation and cytogenetic alterations. Hum Pathol 2002; 33: 484-495.
  4. Hornick JL, Fletcher CD: The significance of KIT (CD117) in gastrointestinal stromal tumors. Int J SurgPathol 2004; 12:93-97.
  5. Anderson J, Meis-Kindblom JM, Stenman G, Aman P, Kndblom LG: The complexity of KIT gene mutations and chromosome rearrangements and their clinical correlation in gastrointestinal stromal (pacemaker cell) tumors. Am J Pathol 2002; 160: 15-22.
  6. Pauls K, Merkelbach-Bruse S, Thal D, Buttner R, Wardmann E: PDGFR-α and c-kit mutated gastrointestinal stromal tumors are characterized by by distinctive and hisological and immunohistochemical features. Histopathology 2005; 46:166-175.
  7. Miettinen M, Wang ZF, Lasota J: DOG1 antibody in the differential diagnosis of gastrointestinal stromal tumors: a study of 1840 cases. Am J Pathol 2009; 33: 1401-1408.
  8. Kaifi JT, Strelow A, Schurr PG, Reichelt U, Yekebas EF, Wachowiak R, Quaas A, Strate T, Schaefer H, Sauter G, Schachner M, Izbicki JR: L1 (CD171) is highly expressed in gastrointestinal tumors. Mod Pathol 2006; 19:399-406
  9. Miettinen M, Lasota J:Gastrointestinal tumors: pathology and prognosis at different sites. SeminDiagnPathol 2006; 23:70-83.

 

Figure 1. GASTRIC GIST

 

 

 

Figure 2: Small Intestine GIST

               A). H&E X 40                           B).IHC CD-117 positive X 40

               C).IHC .CD-34 positive X 40. D).IHC. PDG FR-α positive X 40

 

 

 

 Figure 3: Small Intestine GIST

                 H&E X 40 .Inset .IHC. PDGFR-α positive X 40

 

 

 Figure 4: Small Intestine GIST. H&E X 10

 

Acknowledgements: Rajyalakshmi Associate professors of pathology, Dr. Padma and Dr.P.Sridevi Assistant Professors of Pathology for their continuous support and cooperation in the study. Our Special thanks to Mr.Venkanna Babu, the histopathology technician without whose Support the study would not have been possible.

Source of Support: Nil. Conflict of Interest: None.

 

 

Cite this article as: Krishna L, Rajani V, Rajeswari R, Vijaya Bhaskar R, Sreeramulu Naidu R. Gastrointestinal Stromal Tumors (GISTs) – IHC study and correlation of CD-117 and PDGFR-α staining intensity with histomorphological features –A Study of 8 cases. MRIMS J Health Sciences 2014;2(2):116-118.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 





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