04/08/2020

T6. What I talk when I talk about cutaneous neoplasias?

Summary of contents:

Topic 6 • Basic terminology in tumor pathology

• Questions and reflections to make in front of any biopsy
1. Tumoral or non-tumoral?

What I talk when I talk about 2.

3.
Is it benign or malignant?
Primary or secondary/metastatic?

cutaneous neoplasias? 4.
5.
Is it epithelial, lymphohistiocytic or mesenchymal?
Have I enough material to make a safe diagnosis?
6. Which histochemical techniques can help me?
7. Which immunohistochemical techniques can help me?
María Teresa Fernández Figueras
8. Which molecular techniques can help me?
Hospital Universitari General de Catalunya. Grupo Quironsalud
9. Are they pathognomonic features to distinguish a malignant tumor?
Universitat Internacional de Catalunya
10. Are they unequivocal techniques to distinguish a malignant tumor?

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Basic terminology in tumor pathology Basic terminology in tumor pathology

PARENCHYMA: Tumor cells HYALINIZATION:
• Accumulation of thin

STROMA: Mesenchymal connective collagen bundles

tissue, vessels and inflammatory cells that forming homogeneous

are also an essential part of the tumors aggregates with a

and can contribute to their growth minimal cellularity

• It requires time and

DESMOPLASIA: moderately dense stromal characterizes slow

peritumoral fibroblast proliferation growing lesions

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Basic terminology in tumor pathology Basic terminology in tumor pathology

Invasion: infiltrative pattern
Invasion: expansive pattern
• Spiculated silouette SCC
• Desmoplasia • Rounded silhouette

D SCC • Pushing borders

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Basic terminology in tumor pathology Basic terminology in tumor pathology

Perineural invasion
Mixed pattern of invasion: Perineural space

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Basic terminology in tumor pathology Basic terminology in tumoral pathology

Perineural invasion Intralymphatic invasion
0.12mm 0.05mm

0.08mm 0.13mm

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Basic terminology in tumoral pathology Basic terminology in tumoral pathology

Hematic vascular invasion
Carcinomatous lymphangitis

Fibrin thrombus

Smooth muscle

Tumor cells

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Basic terminology in tumoral pathology Basic terminology in tumoral pathology

Venous vascular invasion Venous vascular invasion

Fibrin thrombus

Smooth muscle

Tumor cells

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Basic terminology in tumoral pathology Basic terminology in tumoral pathology

Typical mitosis Typical mitosis

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Basic terminology in tumoral pathology Questions and reflections to make in front of any biopsy
Typical mitosis 1. Tumoral or non-tumoral?

Atypical mitosis

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Questions and reflections to make in front of any biopsy Questions and reflections to make in front of any biopsy
1. Tumoral or non-tumoral? 1. Tumoral or non-tumoral?
2. Is it benign or malignant? 2. Is it benign or malignant?
3. Is it epithelial, mesenchymal, melanocytic or lymphohistiocytic?

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Questions and reflections to make in front of any biopsy Questions and reflections to make in front of any biopsy
1. Tumoral or non-tumoral? 1. Tumoral or non-tumoral?
2. Is it benign or malignant? 2. Is it benign or malignant?
3. Is it epithelial, mesenchymal, melanocytic or lymphohistiocytic? 3. Is it epithelial, mesenchymal, melanocytic or lymphohistiocytic?
4. Primary or secondary/metastatic? 4. Primary or secondary/metastatic?
5. Have I enough material to make a safe diagnosis?

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Questions and reflections to make in front of any biopsy Questions and reflections to make in front of any biopsy
1. Tumoral or non-tumoral? 1. Tumoral or non-tumoral?
2. Is it benign or malignant? 2. Is it benign or malignant?
3. Is it epithelial, mesenchymal, melanocytic or lymphohistiocytic? 3. Is it epithelial, mesenchymal, melanocytic or lymphohistiocytic?
4. Primary or secondary/metastatic? 4. Primary or secondary/metastatic?
5. Have I enough material to make a safe diagnosis? 5. Have I enough material to make a safe diagnosis?
6. Which histochemical techniques can help me? 6. Which histochemical techniques can help me?
7. Which immunohistochemical techniques can help me? 7. Which immunohistochemical techniques can help me?
8. Which molecular techniques can help me? 8. Which molecular techniques can help me?
9. Are they pathognomonic features to distinguish a malignant tumor?
10. Are they unequivocal techniques to distinguish a malignant tumor?

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1. Tumoral or non-tumoral 1. Tumoral or non-tumoral: typical tumor features

Tumors: Solid or interconnected areas of cellular proliferation

1. Look for typical tumor features

2. Consider the most common tumor simulators

3cm

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1. Tumoral or non-tumoral: typical tumor features 1. Tumoral or non-tumoral: typical tumor features
Tumors: cohesive or interconnected areas of cellular proliferation Tumoral growth: pagetoid

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1. Tumoral or non-tumoral: tumor simulators 1. Tumoral or non-tumoral: tumor simulators

Sporotrichosis Pseudolymphomatous leishmaniasis

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1. Tumoral or non-tumoral: tumor simulators 1. Tumoral or non-tumoral: tumor simulators

Histioid leprosy Hypertrophic scar
&
keloid

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Hypertrophic scar & keloid 2. Is it malignant?

 Nuclear atypia (pleomorphism and hyperchromasia)
 Large and poorly circumscribed
 Ulceration and necrosis
 Invasive growth
 Atypical mitosis
 Desmoplasia
 Lymphovascular invasion
 Perineural invasion

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2. Is it malignant? 3. Is it epithelial, mesenchymal, melanocytic or lymphohistiocytic?

Syringoma Syringomatous carcinoma: deep invasion and Epithelial Mesenchymal Melanocytic Lymphohistiocytic
perineurial growth

Also non-specific patterns 1 2 3 4

such as:
1. pleomorphic
2. clear cell
3. “small round blue”
4. granular cell

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4. Is it metastatic? 5. Have I enough material to make a safe diagnosis?

 Tumor type typical of an extracutaneous location or unexpected
 No connexion with pre-existing structures or benign counterpart
0.4 mm punch biopsy from a

 Only lymphovascular invasion (carcinomatous lymphagiitis) 22 mm keratotic arm lesion

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5. Have I enough material to make a safe diagnosis? 6. Which histochemical techniques can help me?
PAS (red) + mucosecretion and basal membranes Kamino body
Keratoacanthoma in a tattoo
Microcystic adnexal carcinoma
with perineural involvement

1½ month

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7. Which immunohistochemical techniques can help me? 7. Which immunohistochemical techniques can help me?
• Epithelial: keratins, p63, p40, CEA,EMA Epithelial
Keratins (AE1/AE3, 34βE12, …) p63, p40
• Mesenchymal: Vimentin
 Muscle: actin, desmin, caldesmon, caponin
 Neural: s100 protein, neurofilaments, Sox10
 Fibrohistiocytic: CD34, factor XIIIa
 Vascular: CD34, CD31, D2-40, ERG
• Melanocitary: s100, Melan A/Mart1, HMB45, Sox10
• Neuroendocrine: synaptophisin, chromogranin, CD56
• Histiocytic: CD68, CD163, s100, CD1a, Langherin
• Lymphoid: LCA (CD45), B (CD20, CD79a) and T (CD3, CD4, CD8)
• Viral infections: HHV8, MCPyV, p16

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7. Which immunohistochemical techniques can help me? 8. Which molecular techniques can help me?
Proliferative fraction
Ki67
• ISH (In situ hybridization): EBER for Epstein Barr virus detection,
kappa and lambda monotypic populations of plasma cells
• PCR (Polymerase chain reaction): clonality of lymphocytic
populations, HPV detection
• FISH (Fluorescent in situ hybridization): melanomas, sarcomas
• CGH (comparative genomic hybridization): melanoma
• Sequentiation: Detection of targetable oncogenic mutations
• NGS (next generation sequencing): Melanomas and sarcomas

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9. Are they pathognomonic features to distinguish a malignant tumor? 10. Are they unequivocal techniques to distinguish a malignant tumor?

Some
Not a single feature! (although there are false positives and negatives)
(Not even lymph node involvement)
FISH for MDM2 in well-differentiated liposarcomas
Only the combination of several histopathological features in FISH for MYC in well-differentiated angiosarcomas
correlation with the clinical presentation
CGH in melanoma
and others

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“It is a capital mistake to theorize

before you have all the evidence.
It biases the judgment”
Part 1, chap. 3, p. 27

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