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WELCOME TO KMIO
CYTOLOGY DIVISION
DEPARTMENT OF PATHOLOGY
All learning begins with the simple
phrase “I don’t know”
Case 1
53y/F who attended health
checkup camp. Pap smear
IMPRESSION
H S I L
Case 2
Smear for interpretation
Case 1
1. HSIL
2. ASCUS
3. Reactive Changes
4. Atropic Smear with inflammation/ASCUS
5. Inflammatory smear –TV with dysplasia
6. Inflammatory smear-S/O of Herpes
Simplex Inflammation
Case 2
1. Mixed Vaginosis – TV + shift in veginal flora
( cocco bacilli)
2. Mixed inflammation – Bact. Vaginosis + TV
3. Negative for SIL – TV
4. TV, Reactive Cellular Changes Assoc. with
Inflammation
5. TV Infection
6. SCC Cx
IMPRESSION
L S I L + Trichomonos Vaginitis
PAP Test
THE BETHESDA SYSTEM
Adequacy of smear
Cell spread more than 10% of the
slide surface
8000 to 12000 cells in conventional pap
smear/5000 cells in liquid based preparation
Presence or absence of endocervical TZ
component - 10 well preserved, endocervical
or metaplastic cells in singly or in cluster
If abnormal cells seen, never categorize as
unsatisfactory
LSIL
- cells in single/sheets,
- similar to superficial/intermediate cell,
- cytoplasm abundant, eosinophilic/
cyanophilic
- clear cell border
- Nucleus - increase in size 3 times the
nucleus of intermediate cell,
slight irregularity of nuclear outline,
hyperchromasia. Uniform and granular
chromatin, well defined nuclear margin.
No nucleoli
Management: followup, colposcopy HPV test
HSIL
Cell size smaller than the LSIL
Cells in singly/sheets/syncitial
Nuclear abnormalities resemble
parabasal/metaplastic cell,
coarse granular chromatin, no nucleoli,
nuclear margin irregular, decreased
cytoloplasm,
increased N/C ratio
C
ellular ASC
Cellular changes that are more
marked than those attributable to
reactive changes but that
qualitatively and quantitatively fall
short of definitive diagnosis of
ASC
Human Papilloma Virus (HPV)
Vaccine
1. Screening test
2. “ PAP Test “ “VIA” – Good Screening Test
3.“ ASC “ - ? ? ?
4.Ancillary Tests – Colposcopy, HPV test
These are required for management of
women with Cervical Cytological
abnormality
This depends on a good communication
between the Clinician and the
Cytopathologist
Case 3
15y/boy presented with on and off
abdominal pain of 6months and a mass
felt to the left of umbilicus. USG FNA of
the mass done.
1. GCT
2. GCT with Embryonal Carcinoma
3. GCT/ALCL
4. Testicular GCT
5. Pleomorphic Adenocarcinoma-Pancreas
6. HCC
7. High Grade Malignant Tumour
8. ALCL, GCT
Review smears - Poorly differentiated
tumour
Adv. Repeat test at KMIO
Poorly differentiated tumour - ?GCT,
?ALCL
Case will be reviewed after workup
H’gram – Nml
Biochemistry – Nml LDH – 1674 ( 450-N)
Tumour markers – AFP, β-HCG – within Nml
HBsAg & HIV – Non-reactive
USG Abdomen – Enlarged multiple abdominal
mesenteric lymphnodes, largest 3x4x2.5cm
(FNA node) with mild splenomegaly.
Scrotal scan – NAD
No peripheral Lymphadenopathy
Advised IHC on cell block
Lymphnode Biopsy done
LCA
CD3 CD20
CD30
ALK+
PAX5 CD34
CD138
MUM1
Kappa Lamda
Ki67
EMA
CD4
A young boy,
Abdnominal lymphnodes++,
Non- immunocompramised,
H&E- high grade lesion.
IHC
LCA+ CD20-
CD3- CD30-
EMA+ CD34-
CK- CD4 +
ALK+(Granular) LMP1-
CD68- LMP1 ?
CD138- MUM1+
Kappa+ Lamda-
Ki67-65% Pax5 focal+
DIAGNOSIS
FINAL DIAGNOSIS
ALK Positive Diffuse Large B- Cell Lymphoma
ALK Positive Diffuse Large
• B- Cell Lymphoma
•1997 – Delsol workers – Delsol’s Tumour
•Median Age – 36yrs. Paed. – 30%
•High Stage Nodal Disease.
•No Assoc. with immunosuppression
•Poor prognosis – 11months
MORPH: Immunoblastic/plasmablastic,
Sinusoidal infiltration,
Appear deceptively cohesive – D/D Ca
IHC: LCA + 75%, CD+ 3% (weak & focal)
CD79a+ 16%, EMA+ 100%,
CD30+ 6% (weak & focal)
IHC contd
ƛ/ƙ+ 90% (IgA), CD138+/-, CD4+ 64%,
CD57+ 40%, CK+ rare,
ALK+ usually granular cytoplasm
Cytg: t(2:17)(q23;q23) – Fusion of CLTC
(clathrin) gene with ALK gene
t(2:5)(q23;q35)(NPM:ALK) – Rare
EBV – Neg.
NEOPLASIA
ALK-positive diffuse large B-cell lymphoma is
associated with Clathrin-ALK rearrangements:
report of 6 cases
Randy D. Gascoyne, Laurence Lamant, Jose I. Martin-Subero,
Valia S. Lestou, Nancy Lee Harris, Hans-Konrad Mu¨ ller-Hermelink,
John F. Seymour, Lynda J. Campbell, Douglas E. Horsman,
Isabelle Auvigne, Estelle Espinos, Reiner Siebert, and Georges Delsol
Blood. 2003;102:2568-2573
American Journal Clinical Pathology
(2011) Clinical Pathology, 136, 183-194.
Plasmablastic Lymphoma and
Related Disorders
Eric D. Hsi, MD1, Robert B. Lorsbach, MD, PhD2,
Falko Fend, MD3 and Ahmet Dogan, MD, PhD4
+Author Affiliations
1From the Department of Clinical Pathology, Cleveland Clinic, Cleveland, OH;
Department of Pathology, University of Arkansas for Medical Sciences, Little
Rock; 3Institute of Pathology, University Hospital Tuebingen, Eberhard-Karls
University, Tuebingen, Germany and 4Department of Laboratory Medicine a
and Pathology, Mayo Clinic, Rochester, MN
Case 4
28y/F , presented B/L cervical lymphnodes
of 1 – 4cm. in size of 6months duration.
FNA of lymphnodes done
Cytology: Cellular smear,
Lymphoid cells, histiocytes/macrophages,
A few large cells with mono/binucleate,
with prominent nucleoli, ?RS cells
Numerous eosinophils, occ. Plasma cells
DIAGNOSIS
Case 4
1. Histoplasmosis, Kimura’s Disease
2. Lymphoproliferative Diease
3. HD – Mixed Cellularaity
4. LCH
5. HD – Lypmphocytic Predominance
6. SHML with Eo
7. SHML with LCH
8. Kimura’s disease
IMP: Positive Malignancy –
1. Malignant lymphoma, HD/ALCL
2. Metastatic Undifferentiated
Carcinoma
Case will be reviewed after H & N workup
H & N workup was normal
FINAL IMP:
1. Malignant lymphoma, HD/ALCL
2. Histiocytic Lesion
Advised LN Bx and IHC study
CD1a
S100
CD30
CD15
CD30
CD15
Final diagnosis
Hodgkin Lymphoma-syncial type with LCH
Diagnosis of Hodgkin Lymphoma
Diagnosis of LCH
LCH – Systemic or single organ disease
lung, bone, lymphnode, skin, etc.
Cytology findings
Histomorphology –sinusoidal pattern + IHC
LCH+Lymphoma – Focal Langerhan Cell
Histiocytic Hyperplasia rather than LCH
J Res Med Sci. 2010 Jan-Feb; 15(1): 58–61.
Langerhans cell histiocytosis following Hodgkin
lymphoma: a case report from Iran
Nahid Reisi Dehkordi,a Parvin Rajabi,b Azar
Naimi,*,c and Mitra Heidarpourd
Occurrence of LCH after Hodgkin lymphoma
is seen in less than 0.3% of cases.
It can occur before, after or simultaneously
with Hodgkin Lymphoma.
Korean J Intern Med. Dec 2012; 27(4): 459–462.
Langerhans Cell Histiocytosis Followed by
Hodgkin's Lymphoma
IK Soo Park,1 In Keun Park,1 Eun Kyoung
Kim,1 Shin Kim,1 Sang Ryong Jeon,2 Joo Ryung
Huh,3 and Cheol Won Suh 1
This condition should be considered in the differential
diagnosis of recurrent lymphoma
Case 5
• 15yrs boy treated for ALL 6yrs back.
• Regular follow-up
• B/L submandibular cervical lymphadenopathy
2x3cm.
• FNA of the lymphnode done.
List of Differentials
• Reactive lymphoid hyperplasia
• Hemophagocytic lymphohisticytosis
• Recurrent ALL
• Secondary neoplasm : DLBCL
• NHL
Reactive lymphoid hyperplasia
? Significant lymphadenopathy
? Clinical history
Clinically : 2-3cm LN, soft to firm
patient in remission
PS : normal
LDH : normal
Toxoplasma : negative
Clinicians decided to do whole node biopsy to rule out
relapse
IHC : to exclude focal involvement
Tdt : Negative
Correlating clinical, serological and
pathological findings
FINAL DIAGNOSIS
Progressive Transformation of Germinal Centre
Progressive Transformation of Germinal Centre
• Benign reaction pattern in lymph nodes
• Florid or focal
• 3.5% of non specific lymphadenitis
• Pathogenesis premature arrest at an early
transition between primary and secondary
follicles because of incomplete blastic
transformation of B cells.
Progressive Transformation of Germinal Centre
Non hodgkins
• Malignant lymphoma
Hodgkins : NLPHL
• Reactive lymphadenitis
• Immunocompromised
• IgG4 related lymphadenopathy
Thank you….

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Case 1 & 2

  • 1. WELCOME TO KMIO CYTOLOGY DIVISION DEPARTMENT OF PATHOLOGY
  • 2. All learning begins with the simple phrase “I don’t know”
  • 3. Case 1 53y/F who attended health checkup camp. Pap smear
  • 4.
  • 5.
  • 6.
  • 7.
  • 8.
  • 9.
  • 10.
  • 11.
  • 12.
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  • 15. Case 2 Smear for interpretation
  • 16.
  • 17.
  • 18.
  • 19.
  • 20.
  • 21.
  • 22.
  • 23.
  • 24.
  • 25. Case 1 1. HSIL 2. ASCUS 3. Reactive Changes 4. Atropic Smear with inflammation/ASCUS 5. Inflammatory smear –TV with dysplasia 6. Inflammatory smear-S/O of Herpes Simplex Inflammation
  • 26. Case 2 1. Mixed Vaginosis – TV + shift in veginal flora ( cocco bacilli) 2. Mixed inflammation – Bact. Vaginosis + TV 3. Negative for SIL – TV 4. TV, Reactive Cellular Changes Assoc. with Inflammation 5. TV Infection 6. SCC Cx
  • 27. IMPRESSION L S I L + Trichomonos Vaginitis
  • 29. Adequacy of smear Cell spread more than 10% of the slide surface 8000 to 12000 cells in conventional pap smear/5000 cells in liquid based preparation Presence or absence of endocervical TZ component - 10 well preserved, endocervical or metaplastic cells in singly or in cluster If abnormal cells seen, never categorize as unsatisfactory
  • 30. LSIL - cells in single/sheets, - similar to superficial/intermediate cell, - cytoplasm abundant, eosinophilic/ cyanophilic - clear cell border - Nucleus - increase in size 3 times the nucleus of intermediate cell, slight irregularity of nuclear outline, hyperchromasia. Uniform and granular chromatin, well defined nuclear margin. No nucleoli Management: followup, colposcopy HPV test
  • 31. HSIL Cell size smaller than the LSIL Cells in singly/sheets/syncitial Nuclear abnormalities resemble parabasal/metaplastic cell, coarse granular chromatin, no nucleoli, nuclear margin irregular, decreased cytoloplasm, increased N/C ratio
  • 32. C ellular ASC Cellular changes that are more marked than those attributable to reactive changes but that qualitatively and quantitatively fall short of definitive diagnosis of
  • 33.
  • 34. ASC Human Papilloma Virus (HPV) Vaccine
  • 35. 1. Screening test 2. “ PAP Test “ “VIA” – Good Screening Test 3.“ ASC “ - ? ? ? 4.Ancillary Tests – Colposcopy, HPV test These are required for management of women with Cervical Cytological abnormality This depends on a good communication between the Clinician and the Cytopathologist
  • 36.
  • 37. Case 3 15y/boy presented with on and off abdominal pain of 6months and a mass felt to the left of umbilicus. USG FNA of the mass done.
  • 38.
  • 39.
  • 40.
  • 41.
  • 42.
  • 43.
  • 44.
  • 45.
  • 46.
  • 47. 1. GCT 2. GCT with Embryonal Carcinoma 3. GCT/ALCL 4. Testicular GCT 5. Pleomorphic Adenocarcinoma-Pancreas 6. HCC 7. High Grade Malignant Tumour 8. ALCL, GCT
  • 48.
  • 49.
  • 50. Review smears - Poorly differentiated tumour Adv. Repeat test at KMIO Poorly differentiated tumour - ?GCT, ?ALCL Case will be reviewed after workup
  • 51. H’gram – Nml Biochemistry – Nml LDH – 1674 ( 450-N) Tumour markers – AFP, β-HCG – within Nml HBsAg & HIV – Non-reactive USG Abdomen – Enlarged multiple abdominal mesenteric lymphnodes, largest 3x4x2.5cm (FNA node) with mild splenomegaly. Scrotal scan – NAD No peripheral Lymphadenopathy Advised IHC on cell block Lymphnode Biopsy done
  • 52.
  • 53.
  • 54. LCA
  • 56. ALK+
  • 58. MUM1
  • 60. EMA
  • 61. CD4
  • 62. A young boy, Abdnominal lymphnodes++, Non- immunocompramised, H&E- high grade lesion.
  • 63. IHC LCA+ CD20- CD3- CD30- EMA+ CD34- CK- CD4 + ALK+(Granular) LMP1- CD68- LMP1 ? CD138- MUM1+ Kappa+ Lamda- Ki67-65% Pax5 focal+
  • 65. FINAL DIAGNOSIS ALK Positive Diffuse Large B- Cell Lymphoma
  • 66. ALK Positive Diffuse Large • B- Cell Lymphoma •1997 – Delsol workers – Delsol’s Tumour •Median Age – 36yrs. Paed. – 30% •High Stage Nodal Disease. •No Assoc. with immunosuppression •Poor prognosis – 11months
  • 67. MORPH: Immunoblastic/plasmablastic, Sinusoidal infiltration, Appear deceptively cohesive – D/D Ca IHC: LCA + 75%, CD+ 3% (weak & focal) CD79a+ 16%, EMA+ 100%, CD30+ 6% (weak & focal)
  • 68. IHC contd ƛ/ƙ+ 90% (IgA), CD138+/-, CD4+ 64%, CD57+ 40%, CK+ rare, ALK+ usually granular cytoplasm Cytg: t(2:17)(q23;q23) – Fusion of CLTC (clathrin) gene with ALK gene t(2:5)(q23;q35)(NPM:ALK) – Rare EBV – Neg.
  • 69. NEOPLASIA ALK-positive diffuse large B-cell lymphoma is associated with Clathrin-ALK rearrangements: report of 6 cases Randy D. Gascoyne, Laurence Lamant, Jose I. Martin-Subero, Valia S. Lestou, Nancy Lee Harris, Hans-Konrad Mu¨ ller-Hermelink, John F. Seymour, Lynda J. Campbell, Douglas E. Horsman, Isabelle Auvigne, Estelle Espinos, Reiner Siebert, and Georges Delsol Blood. 2003;102:2568-2573
  • 70. American Journal Clinical Pathology (2011) Clinical Pathology, 136, 183-194. Plasmablastic Lymphoma and Related Disorders Eric D. Hsi, MD1, Robert B. Lorsbach, MD, PhD2, Falko Fend, MD3 and Ahmet Dogan, MD, PhD4 +Author Affiliations 1From the Department of Clinical Pathology, Cleveland Clinic, Cleveland, OH; Department of Pathology, University of Arkansas for Medical Sciences, Little Rock; 3Institute of Pathology, University Hospital Tuebingen, Eberhard-Karls University, Tuebingen, Germany and 4Department of Laboratory Medicine a and Pathology, Mayo Clinic, Rochester, MN
  • 71.
  • 72. Case 4 28y/F , presented B/L cervical lymphnodes of 1 – 4cm. in size of 6months duration. FNA of lymphnodes done
  • 73.
  • 74.
  • 75.
  • 76.
  • 77.
  • 78.
  • 79.
  • 80.
  • 81.
  • 82.
  • 83.
  • 84. Cytology: Cellular smear, Lymphoid cells, histiocytes/macrophages, A few large cells with mono/binucleate, with prominent nucleoli, ?RS cells Numerous eosinophils, occ. Plasma cells
  • 86. Case 4 1. Histoplasmosis, Kimura’s Disease 2. Lymphoproliferative Diease 3. HD – Mixed Cellularaity 4. LCH 5. HD – Lypmphocytic Predominance 6. SHML with Eo 7. SHML with LCH 8. Kimura’s disease
  • 87. IMP: Positive Malignancy – 1. Malignant lymphoma, HD/ALCL 2. Metastatic Undifferentiated Carcinoma Case will be reviewed after H & N workup H & N workup was normal FINAL IMP: 1. Malignant lymphoma, HD/ALCL 2. Histiocytic Lesion Advised LN Bx and IHC study
  • 88.
  • 89.
  • 90.
  • 91. CD1a
  • 92. S100
  • 94. CD15
  • 96. Diagnosis of Hodgkin Lymphoma Diagnosis of LCH
  • 97. LCH – Systemic or single organ disease lung, bone, lymphnode, skin, etc. Cytology findings Histomorphology –sinusoidal pattern + IHC LCH+Lymphoma – Focal Langerhan Cell Histiocytic Hyperplasia rather than LCH
  • 98. J Res Med Sci. 2010 Jan-Feb; 15(1): 58–61. Langerhans cell histiocytosis following Hodgkin lymphoma: a case report from Iran Nahid Reisi Dehkordi,a Parvin Rajabi,b Azar Naimi,*,c and Mitra Heidarpourd Occurrence of LCH after Hodgkin lymphoma is seen in less than 0.3% of cases. It can occur before, after or simultaneously with Hodgkin Lymphoma.
  • 99. Korean J Intern Med. Dec 2012; 27(4): 459–462. Langerhans Cell Histiocytosis Followed by Hodgkin's Lymphoma IK Soo Park,1 In Keun Park,1 Eun Kyoung Kim,1 Shin Kim,1 Sang Ryong Jeon,2 Joo Ryung Huh,3 and Cheol Won Suh 1 This condition should be considered in the differential diagnosis of recurrent lymphoma
  • 100.
  • 101. Case 5
  • 102. • 15yrs boy treated for ALL 6yrs back. • Regular follow-up • B/L submandibular cervical lymphadenopathy 2x3cm. • FNA of the lymphnode done.
  • 103.
  • 104.
  • 105.
  • 106.
  • 107.
  • 108.
  • 109.
  • 110.
  • 111. List of Differentials • Reactive lymphoid hyperplasia • Hemophagocytic lymphohisticytosis • Recurrent ALL • Secondary neoplasm : DLBCL • NHL
  • 112. Reactive lymphoid hyperplasia ? Significant lymphadenopathy ? Clinical history Clinically : 2-3cm LN, soft to firm patient in remission PS : normal LDH : normal Toxoplasma : negative Clinicians decided to do whole node biopsy to rule out relapse
  • 113.
  • 114.
  • 115.
  • 116.
  • 117.
  • 118.
  • 119. IHC : to exclude focal involvement Tdt : Negative Correlating clinical, serological and pathological findings
  • 120.
  • 122. Progressive Transformation of Germinal Centre • Benign reaction pattern in lymph nodes • Florid or focal • 3.5% of non specific lymphadenitis • Pathogenesis premature arrest at an early transition between primary and secondary follicles because of incomplete blastic transformation of B cells.
  • 123. Progressive Transformation of Germinal Centre Non hodgkins • Malignant lymphoma Hodgkins : NLPHL • Reactive lymphadenitis • Immunocompromised • IgG4 related lymphadenopathy

Editor's Notes

  1. Lymphoid cells of mantle zone are migrating into the germinal centre disrupting it and causing expansion of GC
  2. Disruption of mantle zone and Expansion of germinal center