Conferencia de la Dra. Anaís Malpica durante el XVII Congreso Venezolano de Oncología 2016. Valencia

1. Cervical Cancer: Relevant Issues
Valencia, Venezuela 2016
Anaís Malpica, M.D.
Professor
Department of Pathology

2. Case # 1
• 34 year-old woman with atypical
glandular cells on a routine Pap smear
• ECC was obtained

4. Fragment of neoplastic epithelium with numerous apoptotic bodies

5. Detached fragments of adenocarcinoma

7. Synaptophysin +

8. Chromogranin +

9. CD56 -

10. NKX2.2 +

11. p40 -

12. Diagnosis
Fragments of Adenocarcinoma and High
Grade Large Cell Neuroendocrine
Carcinoma

13. Neuroendocrine Carcinoma
• When to think
about it?
 Histologic
features
 Cervical tumor
with an
aggressive
behavior

14. Nests and trabeculae of tumor cells
Large Cell Neuroendocrine Carcinoma

15. Irregular distribution of the chromatin, prominent nucleoli,
numerous apoptotic bodies and mitoses

16. Chromogranin + Synaptophysin + p40 -

17. Geographic necrosis

18. Trabecular pattern

19. Nest with focal glandular formation

20. Small Cell Neuroendocrine Carcinoma

21. Scanty cytoplasm, “salt and pepper chromatin”, numerous
apoptotic bodies and mitoses

22. Neuroendocrine Carcinoma
• Large Cell Neuroendocrine Carcinoma
 Young patients, average age: 34 years
(range, 21 to 75 years)
• Small Cell Neuroendocrine Carcinoma
 Patients with a wide age range,
22 to 86 years
(median 43 or 46 years)
• Associated with HPV 18
or HPV 16
High risk HPV detected by in hybridization

23. Neuroendocrine Carcinoma of Cervix,
IHC
• Keratin expression:
 Keratin AE1/AE3 +
- + in most cases, but not in all cases
 Keratin 7 + (50% of cases)
 Keratin 20 + (9% of cases)
• PAX-8 - (limited experience)

24. Neuroendocrine Carcinoma of Cervix,
IHC
• Neuroendocrine markers:
 CD56 +, 90% of cases
 Synaptophysin +, 90% of cases
 Chromogranin +, 50% of cases

25. Neuroendocrine Carcinoma of Cervix,
IHC
• TTF-1+, 70% of cases
• Her 2-neu (+) 50% of cases (small cell
carcinoma)
• CD99 and neurofilament can be +
• Role of other immunomarkers of NE
differentiation has not been explored
 ASH1
 NKX2.2

26. Neuroendocrine Carcinoma of Cervix,
IHC
• Markers of squamous differentiation:
 p63 can be + (43% of cases)
 p40 usually negative (limited
experience in cervix, but in lung <5%
cases +)
 Keratin 5/6, usually negative (limited
experience in cervix, but in lung rare
cases +)

27. Confounding Factors
Mixed histotypes
IHC studies results
Failure to recognize cardinal
features

28. Be attentive, neuroendocrine carcinoma can be part of a mixed
carcinoma

29. CD56 + Syn +

30. Mixed Carcinoma, Adenocarcinoma and Large Cell Neuroendocrine
Carcinoma

32. Chr +

33. CD56+

34. Syn+

36. P16 +

37. p63 -

39. Gyn Pathologist’s dx, Adenosquamous Carcinoma

40. Chr +
Syn +
CD56 +
Correct Dx: Large Cell Neuroendocrine Ca

41. p40 -

42. Small cell neuroendocrine carcinoma can be positive for p63

43. p63 + TTF-1+
PAX-8 -

44. Metastatic Carcinoma in the Lung
Misinterpreted as Colorectal in Origin
Keratin 20 +
Correct Dx: Metastatic Large Cell
Neuroendocrine Ca from the Cervix

45. Cervical Tumor with an Aggressive
Behavior
• Neuroendocrine carcinomas are highly
aggressive tumors
 Even if they represent a small
component of a mixed carcinoma of the
cervix
• Hematogenous spread
 Metastases to lungs, liver, brain, bones,
mesenteric and para-aortic lymph
nodes

46. 26 yo female with cervical carcinoma and brain metastasis

47. 26 yo female with cervical carcinoma and brain metastasis

48. Large cell neuroendocrine carcinoma initially interpreted as poorly
differentiated squamous carcinoma

49. Large cell neuroendocrine carcinoma initially interpreted as poorly
differentiated squamous carcinoma

50. Chromogranin +

51. p40 -

52. Differential Diagnosis: Poorly Differentiated Squamous Carcinoma

53. Syn - CD56 -Chr -
Differential Diagnosis: Poorly Differentiated Squamous Carcinoma

54. Differential Diagnosis: Adenosquamous carcinoma with basaloid features

55. p63 focally +

56. Ker 5/6 +

57. Syn - Chr - CD56 -

58. Case # 2
• A 36 year-old woman presented with
vaginal bleeding
• Physical examination was
unremarkable
• An endometrial biopsy was obtained

59. Endometrial Biopsy

60. Endometrial Biopsy

61. • Diagnostic “flip-flop”
 Dx #1
- Endometrial endometrioid adenocarcinoma,
FIGO grade 1
 Dx #2
- Adenocarcinoma, probable arising in the
cervix and of mesonephric in origin
 Dx #3
- Endometrial endometrioid adenocarcinoma,
FIGO grade 1
Initial Diagnoses

62. Exophytic Tumor in Cervix, Total Abdominal Hysterectomy Specimen

63. Exophytic Tumor in Cervix, Total Abdominal Hysterectomy Specimen

64. Invasion into the cervical wall without desmoplastic reaction

65. Tumor Extending to the Exocervical
Margin

66. Vimentin +

67. Calretinin +

68. Diagnosis
Mesonephric Adenocarcinoma

69. Mesonephric Adenocarcinoma
• Rare tumor that should not be mistaken
for endometrial adenocarcinoma
• Patients’ ages range from 24 to 72 years
 average, 53 years
• Symptoms
 Vaginal bleeding
 Absent
• Gross
 Polypoid tumor
 Enlargement of the cervical wall
 Less frequently, there is no gross alteration

70. -CD 10 + (usually focal and with a luminal
pattern)
•CD10 can be positive in cervical and
endometrial adenocarcinomas
-Calretinin +
-Vimentin +
-PAX-8 +
-GATA-3 +
Mesonephric Adenocarcinoma
Immunoperoxidase Studies
Roma A, et al 2015

71. Immunoperoxidase Studies
-Inhibin + (focal)
-p16 + (usually focal)
-Androgen receptor can be +
-CEA usually negative
-ER usually negative
Mesonephric Adenocarcinoma

72. Prognosis
• Most cases are stage I and with a more indolent
course than the one seen in mullerian
adenocarcinomas of the uterine cervix
• Tendency to late recurrences
• The tumor has an aggressive behavior in the few
cases that present at an advanced stage
Mesonephric Adenocarcinoma

73. Prognosis
• Most cases are stage I and with a more indolent
course than the one seen in mullerian
adenocarcinomas of the uterine cervix
• Tendency to late recurrences
• The tumor has an aggressive behavior in the few
cases that present at an advanced stage
Mesonephric Adenocarcinoma

74. Case # 3
• A 47 year-old female presented
with vaginal bleeding
• An endometrial biopsy was obtained
 Endometrial endometrioid
adenocarcinoma, FIGO grade 1
• TAHBSO
 2 cm tumor in the upper endocervical
canal

81. CEA +

82. Vimentin -

83. ER - PR -

84. p16 -

85. Loss of DPC4

86. Napsin A
-

87. PAX8 +

89. Diagnosis
Invasive Adenocarcinoma of the Uterine
Cervix, Mucinous Differentiation/Gastric
Type

90. Endocervical adenocarcinoma, usual type

91. Endocervical adenocarcinoma, usual type

92. Mucinous carcinoma, gastric type (minimal deviation adenocarcinoma)

93. Mucinous carcinoma, gastric type (minimal deviation adenocarcinoma)

94. The more opinions
you have, the less you
see.
Wim Wenders