This slide presentation summarizes the cytology findings of a liver biopsy from a 60-year-old male. Giemsa stained smears showed moderately cellular tumor cells arranged in clusters and fragments with ill-defined edges. The tumor cells had round to oval nuclei and granular cytoplasm. Background showed lymphocytes and hemorrhage. A diagnosis of metastatic tumor was made, with the top differential diagnoses being metastatic papillary urothelial carcinoma, neuroendocrine tumor, solid pseudo-papillary neoplasm of the pancreas, or epithelioid gastrointestinal stromal tumor. Additional slides showed examples of various liver lesions and metastases that can present on cytology to aid in diagnosis.

1. SLIDE PRESENTATION
CYTOLOGY
Sansar Babu Tiwari, MBBS, PGY II
Department of Pathology
TUTH
17th March 2021
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2. One giemsa stained smear of liver nodule in a 60-year-old male.
Smears are moderately cellular in a predominantly clean background.
Tumor cells are arranged in loosely cohesive clusters, papillary
fragments, acini and rosette along with few scattered cells. The edges of
clusters are ill defined.
These cells are round to oval with moderate amount of granular
cytoplasm.
Nuclei are mildly pleomorphic and are centrally placed. They are round to
oval with regular outline.
SLIDE PRESENTATION
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3. The chromatin is coarse to clumped.
These cells have inconspicuous nucleoli.
Background shows mature lymphocytes and hemorrhages.
Mitosis is infrequent.
SLIDE PRESENTATION
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4. Giemsa stain
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5. Giemsa stain 5

6. Giemsa stain 6

7. Giemsa stain
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8. Giemsa stain
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9. Giemsa stain
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10. Giemsa stain
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11. Giemsa stain
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12. Giemsa stain
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13. Giemsa stain
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14. Diagnosis:
1. Metastatic tumor.
Differential Diagnosis:
1. Metastatic papillary urothelial carcinoma.
2. Metastatic Neuroendocrine tumor
3. Metastatic Solid Pseudo-papillary Neoplasm of Pancreas
4. Metastatic Epithelioid GIST
SLIDE PRESENTATION
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15. 15
DISCUSSIONS

16. Liver Metastasis
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• Liver is the most common site of metastasis.
• Colon, breast, lung and pancreas are the
common site.
• Virtually any tumor may spread to the liver.

17. Commonly encountered in FNAB
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• Colorectum
– Adenocarcinoma
• Pancreas
– Adenocarcinoma
– NET
• Stomach
– Adenocarcinoma
– GIST
• Breast and lung
– Adenicarcinoma, small cell carcinoma and SCC

18. Commonly encountered in FNAB
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• Skin
– Melanoma
• Bladder
– Urothelial cell carcinoma
• Lymphoma
• Uterus
– Uterine leiomyosarcoma
• Diagnostically challenging are:
– Metastases from kidney and adrenal gland
• Due to morphological overlap to HCC.

19. Finding the Roots:
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• Why is it essential to know the morphology
and find the origin?
– To dictate targeted chemotherapy and an
understanding of the disease prognosis.
• There is literature that states that a diagnosis
can be determined upon morphology alone
– However, a series of additional biomarkers such as
cytokeratins, S100, and leukocyte-common
antigen (LCA) may assist in further categorizing
the specific organ of origin.
• Major bulk: HCC vs metastatic
adenocarcinoma.

20. Finding the Roots:
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• C-kit, CD34, and Vimentin have correlations
with GISTs.
• Malignant melanomas: S100+, HMB45,
Melan-A and MART-1
• Neuroendocrine carcinomas: Synaptophysin,
Chromogranin, and CD56.
• CK7 and CK20 have been used as initial
differentiating markers for tumor origin
• Estrogen receptors in the case of metastatic
lobular breast carcinoma.

21. Where’s the primary?
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• 10 years study in Netherlands: 23000 patients with liver mass.
• Most common metastases originated from
– Colorectal primaries
– Pancreatic
– Breast
• In females less than 50 years of age, metastatic hepatic disease
originated more frequently from the breast
• Oder than 70 years old were from a gastrointestinal source
• 92% of metastatic hepatic lesions were carcinomas.
75% of them were adenocarcinomas.
• Overall, histologically confirmed hepatic metastases were more
common in males than females, and the majority of patients were
older than 50 years of age.

22. Integrative approach for evaluation of
liver aspirates
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1. Evaluate clinical information:
– Relevant clinical findings
– Liver function test
– Serology
– Tumor markers

23. Integrative approach for evaluation of
liver aspirates
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2. Evaluate radiological information:
– Cystic or solid
– Single or multiple
– Any preexisting or chronic hepatobiliary disease
3. Evaluate cytohistologic findings:
– Low power to evaluate pattern and architecture
– Solid or cystic
– Benign or malignant.

24. Integrative approach for evaluation of
liver aspirates
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4. Evaluate ancillary studies:
– When there is scant material, cytomorphology
becomes crucial.
5. Correlate all previous steps:
– Clinicopathological correlation is mandatory to
arrive at a final definitive diagnosis
– An indeterminate diagnosis may be rendered for
very-well-differentiated hepatocellular nodules.

25. Bottom line
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Information obtained from all of the previous
steps, including a complete IHC workup, may
helps
• To establish a generic morphological diagnosis
for non hepatocellular lesions
• But not provide the specific organ of origin.

26. Algorithm
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• Hepatocellular appearance
– Focal fatty change
– Large regenerative nodule
– Dysplastic nodule (low or high grade)
– Siderotic nodule (regenerative, dysplastic)
– Focal nodular hyperplasia
– Hepatocellular adenoma
– Hepatocellular carcinoma, variants and special types
– Hepatoblastoma
– Hepatocellular and glandular appearance
– Combined hepatocellular and cholangiocarcinoma

27. Algorithm
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• Nonhepatocellular appearance
– Glandular pattern: bile duct hamartoma, bile duct
adenoma (peribiliary gland hamartoma),
intrahepatic cholangiocarcinoma, combined
hepatocellularcholangiocarcinoma, metastases
– Squamous, including adenosquamous, pattern:
Intrahepatic cholangiocarcinoma, metastases
– Oncocytic cell pattern: angiomyolipoma,
metastases (renal cell carcinoma, adrenocortical
carcinoma), melanoma

28. Algorithm
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• Nonhepatocellular appearance
– Small cell pattern: neuroendocrine tumor,
lymphoma, metastases (small cell carcinoma,
lobular carcinoma of breast, melanoma),
inflammatory pseudotumor
– Large cell pattern: neuroendocrine carcinoma,
metastases (undifferentiated carcinoma)

29. Algorithm
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• Nonhepatocellular appearance
– Spindle cell pattern: cavernous hemangioma,
infantile hemangioma, solitary fibrous tumor,
inflammatory pseudotumor, angiomyolipoma,
gastrointestinal stromal tumor, sarcomatoid
carcinoma (including primary liver carcinomas and
metastatic sarcomatoid renal cell carcinoma),
sarcoma (primary and metastatic, including
angiosarcoma, Kaposi sarcoma, carcinosarcoma,
hepatobiliary rhabdomyosarcoma, synovial
sarcoma and leiomyosarcoma)

30. Algorithm
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• Nonhepatocellular appearance
– Mucinous pattern: mucinous cystic neoplasm,
intrahepatic cholangiocarcinoma, metastases
– Papillary pattern: intraductal papillary neoplasm,
intrahepatic cholangiocarcinoma, metastases
– Clear cell pattern: angiomyolipoma, metastases
(renal cell carcinoma, adrenocortical carcinoma)

31. Biliary intraductal papillary neoplasm
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32. Biliary intraductal papillary neoplasm
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33. Biliary intraductal papillary neoplasm
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34. Cavernous hemangioma
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35. Cavernous hemangioma
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36. Mesenchymal Hamartoma
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37. Large regenerative nodule
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38. Solid Pseudopapillary Neoplasm
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39. Solid Pseudopapillary Neoplasm
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• Metastasis or recurrence of liver is the main
factor affecting the survival of patients with
SPTM.
• In one study cohort, 26 out of 159 patients died
of uncontrollable liver metastasis, including 6
simultaneous metastasis and 20 postoperative
relapses.
• Therefore, the early detection of liver metastasis
for surgical resection is particularly important.

40. Large cell changes
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41. Small cell changes
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42. Hepatocellular carcinoma
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43. Hepatocellular carcinoma
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44. HCC with fatty change
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45. HCC with small cell changes
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46. Colonic adenocarcinoma
• Cigar-shaped, often palisaded nuclei
• Variably prominent nucleoli but not
macroeosinophilic nucleoli
• Dirty necrosis in the background
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47. Colonic adenocarcinoma
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48. Breast adenocarcinoma
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49. Colonic adenocarcinoma
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50. Melanoma
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51. • Large polygonal cells singly and in clusters; may
also be spindled or small blue cells with scant
cytoplasm
• Central to eccentric nuclei with large nucleoli
• Intranuclear inclusions common
• Cytoplasm is commonly abundant, non-granular
and frequently non-pigmented
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Melanoma

52. Renal cell carcinoma
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53. Neuro endocrine tumor
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54. • Small uniform blue cells with scant cytoplasm
perinuclear in carcinoid tumors and more
abundant and eccentric in PEN
• Nuclei with coarse stippled chromatin, more
obvious in carcinoids than PEN
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Neuro endocrine tumor

55. • Stromal alterations:
– WDNETs of stomach can exhibit myxoid features.
– Most of them are stroma poor and are fleshy in
cut section,
• However, can exhibit stromal sclerosis in ileal and Pan
NETs which secretes serotonin.
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Neuro endocrine tumor

56. Small cell carcinoma
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57. GIST
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58. Epithelioid GIST
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59. Epithelioid GIST
• GISTs most frequently metastasize within the
abdominal cavity, especially to the liver and
peritoneum, with bone and lung metastases
being uncommon sites.
• Myxoid stroma
• Increased vascularity
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60. Leiomyosarcoma
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61. • Pleomorphic spindle cells in tightly cohesive
three-dimensional groups and syncytia;
• No prominent vascular pattern
• Hyperchromatic, pleomorphic nuclei with
blunted nuclear ends
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Leiomyosarcoma

62. Adrenocortical carcinoma
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63. Take home messages:
1. Epithelioid GIST can resemble adenocarcinoma
when they form glands and acini.
2. SPN with low malignant potential can
metastasize to liver and should be detected to
avoid the complications for resection. (>5cm)
3. Metastatic NET of GI is common than primary
NET of liver
1. Mxoid stroma suggests origin as stomach
2. Sclerosis suggests ileal origin.
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64. • Thank you!!!
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