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Tumors with Differentiation to Hair Follicular Structures

Supported by the Savannah and Barry French Poodle Memorial Fund
University of Pennsylvania School of Veterinary Medicine

Michael H. Goldschmidt, MSc, BVMS, MRCVS, Diplomate ACVP Professor and Head, Laboratory of Pathology and Toxicology Chief, Surgical Pathology Department of Pathobiology
Frances S. Shofer, PhD, Adjunct Associate Professor of Epidemiology and Biostatistics

Introduction

These tumors show differentiation to hair follicular structures. There is a marked variability in the histopathologic appearance of these tumors, and there may be some variability within a single tumor when examined by light microscopy. This variability is due to the complex histology of the normal hair which is mimicked by these tumors showing hair follicular differentiation.

During embryologic development of the skin and adnexal structures the pilar germ emerges at an angle from the underside of the epidermis. Under the influence of inductive mesenchymal cells, which will form the papillum of the hair, the cells extend into the deep dermis. Here differentiation of the hair germ in to the hair bulb occurs. The hair shaft, the outer root sheath and inner root sheath are formed from the hair bulb.

Infundibular Keratinizing Acanthoma (IKA)

Introduction

Definition: A benign tumor characterized by peripheral proliferation of basaloid epithelial cells with differentiation to squamous epithelium resembling the normal follicular infundibulum/isthmus.

Synonyms: Intracutaneous Cornifying Epithelioma (ICE), Squamous Papilloma

Epidemiology

Sex N Percent
Female 377 18% (21%)
Female Spayed 730 35% (33%)
Male 544 26% (25%)
Male Castrated 454 21% (21%)
(Normal Population %)

Breeds at
Increased Risk
N Probability OR 95%
Confidence Interval
Norwegian Elkhound 106 <0.0001 32.1 25.8 39.9
Tibetan Terrier 16 <0.0001 14.8 8.8 24.9
Kerry Blue Terrier 34 <0.0001 9.8 6.9 14.0
Pekingese 33 <0.0001 5.7 4.0 8.1
Briard 7 0.00076 4.9 2.3 10.5
German Shepherd 343 < 0.0001 4.6 4.1 5.2
Bearded Collie 6 0.00410 4.1 1.8 9.4
Yorkshire Terrier 86 <0.0001 3.5 2.8 4.4
Bichon Frise 50 <0.0001 3.4 2.5 4.5
Lhasa Apso 74 <0.0001 3.4 2.7 4.3
Keeshond 20 0.00031 2.5 1.6 3.9
Old English Sheepdog 22 0.00120 2.2 1.4 3.4
Samoyed 21 0.00180 2.2 1.4 3.3
Shetland Sheepdog 80 <0.0001 2.0 1.6 2.6
Australian Shepherd 11 0.02940 2.0 1.1 3.7
Standard Poodle 47 0.00012 1.9 1.4 2.5
Miniature Schnauzer 42 0.03330 1.4 1.0 1.9

Breeds at
Decreased Risk
N Probability OR 95%
Confidence Interval
Dachshund 16 0.0257 0.58 0.36 0.95
Siberian Husky 16 0.0058 0.52 0.32 0.85
Beagle 21 0.0002 0.48 0.31 0.73
Golden Retriever 67 <0.0001 0.42 0.33 0.54
Cocker Spaniel 33 <0.0001 0.34 0.24 0.48
Dalmatian 5 0.0024 0.31 0.13 0.74
American Pit Bull Terrier 3 0.0050 0.25 0.08 0.77
German Shorthaired Pointer 3 0.0020 0.22 0.07 0.69
Great Dane 3 0.0005 0.20 0.07 0.63
West Highland White Terrier 4 <0.0001 0.20 0.07 0.52
Labrador Retriever 35 <0.0001 0.19 0.14 0.27
Scottish Terrier 2 <0.0001 0.13 0.03 0.52
Basset Hound 2 < 0.0001 0.09 0.02 0.38
Rottweiler 4 <0.0001 0.08 0.03 0.22
Shar-Pei 1 <0.0001 0.08 0.01 0.55
Doberman Pinscher 4 < 0.0001 0.07 0.02 0.18
Boxer 2 <0.0001 0.03 0.01 0.13

Site Percent
Back 15.0%
Forelimb 13.4%
Hindlimb 13.2%
Tail 12.0%
Neck 10.5%
Head 9.9%
Multiple 9.7%
Thorax 8.9%
Abdomen 6.4%
Perineum 1.0%

OncoLink Veterinary Cancer Resources

Clinical Presentation/Physical Exam Findings

  • Intradermal mass(es)
  • Often exophytic
  • Varying in size from 0.5-3.0 cm
  • Often have a central pore through which a grey keratinous material may be expressed
  • A proportion of tumors do not have a central pore and consist of intradermal and subcutaneous masses.
  • Intradermal and subcutaneous component well demarcated from surrounding tissue

Tumor Pathology

Gross Findings

  • Tumors with pores associated with the skin have a flask shaped mass at their base.
    • It is filled with gray-brown keratin.
  • There is a sharp demarcation between tumor tissue and normal surrounding tissues.
  • Those tumors without a pore have keratin accumulation in the center of the mass.
    • Although the tumor tissue is still well-demarcated, the peripheral rim of tissue is thinner in this type of tumor.
  • There may be inflammation in the surrounding tissue due to the escape of keratin from the tumor; here it acts like a foreign body.

Microscopic Findings

  • Central lumen filled with keratin
  • Lined by large squamous cells with a pale eosinophilic cytoplasm
  • Occasional intracytoplasmic keratohyalin granules
  • Cells have a central large euchromatic nucleus and distinct cell borders
  • At the periphery the tumor cells often form cords only two cells thick
  • Differentiate towards the central lumen, form multiple small horn cysts
  • Tumor is surrounded by a compressed dermal collagenous stroma
  • Often an associated chronic inflammatory cell infiltrate
  • Occasionally, tumors exhibit stromal mucinosis
  • May also show chondroid or osseous metaplasia

Clinical Behavior

Solitary tumors can be cured by wide excision. Those dogs that have multiple tumors are prone to continue to develop more.

Tricholemmoma

Definition: A benign follicular tumor characterized by external root sheath differentiation, with a predominance of either the inferior segment of the external root sheath (inferior type) or the isthmus segment of the external root sheath (isthmic type).

Subtypes: Inferior Tricholemmoma, Isthmic Tricholemmoma

Epidemiology

Sex N Percent
Female 12 20% (21%)
Female Spayed 22 36% (33%)
Male 11 18% (25%)
Male Castrated 16 26% (21%)
(Normal Population %)

Site Percent
Head
30.5%
Forelimb
15.3%
Hindlimb
11.9%
Thorax
11.9%
Neck
10.2%
Multiple Sites
8.5%
Back
5.0%
Tail
5.0%
Perineum
1.7%

OncoLink Veterinary Cancer Resources

Clinical Presentation / Physical Exam Findings

  • These tumors cannot be distinguished from trichoblastomas (formerly basal cell tumors) on clinical evaluation
  • Both trichoblastoma and tricholemmoma present as an elevated mass varying in size from 1-5 cm in diameter
  • The overlying epidermis is alopecic, thin, and hyperpigmented, and may be ulcerated

Tumor Pathology

Gross Findings

  • Tricholemmoma may also be difficult to distinguish from trichoblastoma on gross examination
  • Both tumors are often multilobulated on cut section and well demarcated from surrounding tissue

Microscopic Findings

Inferior type

  • Composed of islands of neoplastic cells separated by a fine fibrillar collagenous stroma
  • Prominent eosinophilic basal lamina zone
  • Peripheral cells are palisaded and have abundant pale eosinophilic cytoplasm
  • Central cells have abundant deeply eosinophilic cytoplasm
  • Cells show little pleomorphism or mitotic activity

Isthmic type

  • Composed of epithelial aggregates
  • May be an association with the epidermis
  • Cords of epithelial cells radiate out from and often join islands of epithelial cells, which show central tricholemmal keratinization
  • Large islands may appear cystic
  • Cells have moderate amount of lightly eosinophilic, glassy cytoplasm with small euchromatic nuclei
  • Tumors may be heavily melanized

Clinical Behavior

Tricholemmomas are benign tumors and respond well to surgical excision, recurring rarely.

Trichoblastoma

Introduction

Definition: A benign neoplasm derived from or reduplicating the primitive hair germ of embryonic follicular development.

NOTE: These were previously classified as basal cell tumors.

Epidemiology

Sex N Percent
Female 695 17% (21%)
Female Spayed 1240 31% (33%)
Male 1072 27% (25%)
Male Castrated 995 25% (21%)
(Normal Population %)    

Breeds at
Increased Risk
N Probability OR 95%
Confidence
Interval
Kerry Blue Terrier 67 <0.0001 11.0 8.5 14.3
Bichon Frise 141 <0.0001 5.3 4.4 6.3
Bedlington Terrier 5 0.0119 3.9 1.6 9.5
Cockapoo 64 <0.0001 3.7 2.9 4.8
Shetland Sheepdog 249 <0.0001 3.5 3.1 4.0
Puli 5 0.0199 3.4 1.4 8.3
Bearded Collie 9 0.0023 3.3 1.7 6.5
Husky 132 <0.0001 2.4 2.0 2.8
Miniature Poodle 207 <0.0001 2.2 1.9 2.5
Soft-Coated Wheaton Terrier 23 0.0024 2.0 1.3 3.1
Cocker Spaniel 318 <0.0001 1.9 1.7 2.1
Collie 55 0.0004 1.7 1.3 2.2
Yorkshire Terrier 75 0.0004 1.6 1.2 2.0
English Springer Spaniel 92 0.0005 1.5 1.2 1.8
West Highland White Terrier 54 0.0135 1.4 1.1 1.9
Scottish Terrier 12 0.0006 0.4 0.2 0.7

Breeds at
Decreased Risk
N Probability OR 95%
Confidence
Interval
Doberman Pinscher 38 <0.0001 0.33 0.24 0.46
Basset Hound 13 <0.0001 0.32 0.19 0.55
Jack Russell Terrier 6 0.0007 0.31 0.14 0.69
Dachshund 16 <0.0001 0.30 0.19 0.50
Miniature Schnauzer 17 <0.0001 0.29 0.18 0.47
Beagle 22 <0.0001 0.26 0.17 0.39
Standard Schnauzer 8 <0.0001 0.26 0.13 0.51
Labrador Retriever 85 <0.0001 0.25 0.20 0.31
Chihuahua 4 0.0001 0.21 0.08 0.55
Akita 3 0.0002 0.18 0.06 0.57
Pug 3 0.0001 0.18 0.06 0.54
Pointer 1 0.0354 0.17 0.02 1.18
Rottweiler 11 <0.0001 0.12 0.07 0.22
German Shepherd 3 <0.0001 0.12 0.04 0.36
Weimeraner 2 <0.0001 0.10 0.03 0.41
Mastiff 1 0.0016 0.10 0.01 0.72
Boston Terrier 2 <0.0001 0.09 0.02 0.37
Vizsla 1 0.0005 0.09 0.01 0.65
Shar-Pei 2 <0.0001 0.08 0.02 0.32
Boxer 7 <0.0001 0.06 0.03 0.12
Great Dane 1 <0.0001 0.04 0.00 0.25

Site Percent
Head
61.9%
Forelimb
12.9%
Neck
12.7%
Hindlimb
5.6%
Thorax
2.5%
Back
1.3%
Abdomen
1.1%
Tail
1.0%
Perineum
0.7%
Multiple Sites
0.3%

OncoLink Veterinary Cancer Resources

Although these tumors were previously classified as basal cell tumors there is no known association with excessive UV light exposure.

Clinical Presentation/Physical Exam Findings

  • Elevated mass
  • Varies in size from 1-5 cm in diameter 
  • Overlying epidermis alopecic, thin and hyperpigmented 
  • May be ulcerated 
  • Head and neck most common site of tumor

Tumor Pathology

Gross Findings

  • Often multilobulated on cut section 
  • Well demarcated from surrounding tissue
  • May be pigmented and/or cystic

Microscopic Findings

Histopathology: There are several histologic subtypes of trichoblastomas. All of these tumors are benign.

  • Ribbon
  • Medusoid
  • Granular cell
  • Trichogenic

Ribbon type

  • Consists of long cords of cells which branch and join together
  • Cords are often only two cells thick with the nuclei arranged in a palisaded fashion perpendicular to the long axis of the column.
  • Nuclei are euchromatic to hyperchromatic.
  • Number of mitoses is variable, but may be high
  • Individual cells have only small amount of pale eosinophilic cytoplasm with indistinct cell borders
  • Surrounding collagenous matrix may be quite extensive and appear hyalinized.

Medusoid type

  • similar to the ribbon type
  • Consists of cords of cells radiating from a central island of densely packed cells.
  • These tumors have a more abundant eosinophilic cytoplasm.

Granular cell type

  • cells have an abundant, finely granular, eosinophilic cytoplasm
  • eccentrically located small hyperchromatic nuclei
  • variable amount of collagenous stroma may be present 

Trichogenic type

  • islands of cells with foci of incomplete trichogenesis

Cytology

  • Small to medium-sized cells
  • Very adherent, difficult to find isolated cells 
  • Uniform cell population 
  • High N:C ratio
  • Round nuclei, moderately dense chromatin; indistinct nucleoli; small amount of blue cytoplasm
  • May or may not see melanin pigment granules

Clinical Behavior

These tumors have an excellent prognosis; they are slow growing. There are no reported cases of metastasis. Some dogs will present with more than one mass, but this is not metastasis. They do not recur following wide excision.

Trichoepithelioma

Definition: A benign follicular tumor with differentiation to all three segments of the hair follicle (bulb, internal root sheath and external root sheath), in which incomplete or abortive trichogenesis is present.

Epidemiology

Sex N Percent
Female 1136 23% (21%)
Female Spayed 2106 43% (33%)
Male 964 19% (25%)
Male Castrated 726 15% (21%)
(Normal Population %)    

Breeds at
Increased Risk
N Probability OR 95% Confidence
Interval
Otterhound 9 <0.0001 24.2 10.9 53.9
Mastiff 54 <0.0001 5.1 3.9 6.7
Bullmastiff 38 <0.0001 4.5 3.2 6.2
Golden Retriever 942 <0.0001 3.1 2.9 3.4
Standard Poodle 169 <0.0001 3.0 2.5 3.5
Gordon Setter 25 <0.0001 2.6 1.7 3.9
Irish Setter 85 <0.0001 2.5 2.0 3.1
English Springer Spaniel 188 <0.0001 2.5 2.2 2.9
Standard Schnauzer 72 <0.0001 1.9 1.5 2.4
Weimeraner 39 0.0021 1.7 1.2 2.3
Miniature Schnauzer 111 <0.0001 1.7 1.4 2.0
Saint Bernard 17 0.0461 1.6 1.0 2.6
Dalmatian 62 <0.0001 1.6 1.2 2.1

Breeds at
Decreased Risk
N Probability OR 95% Confidence
Interval
Mixed Breed 987 <0.0001 0.79 0.74 0.85
West Highland White Terrier 35 0.0419 0.71 0.51 0.99
Boxer 84 <0.0001 0.63 0.52 0.78
Collie 24 0.0024 0.55 0.37 0.83
American Pit Bull Terrier 12 0.0026 0.47 0.28 0.80
Labrador Retriever 191 <0.0001 0.45 0.39 0.52
Cocker Spaniel 96 <0.0001 0.45 0.37 0.54
Toy Poodle 9 0.009 0.44 0.23 0.85
Jack Russell Terrier 10 0.0014 0.40 0.21 0.74
Dachshund 24 <0.0001 0.37 0.25 0.55
Rottweiler 39 <0.0001 0.34 0.25 0.46
Samoyed 7 0.0002 0.33 0.16 0.66
Cairn Terrier 8 <0.0001 0.33 0.16 0.66
Alaskan Malamute 4 0.0129 0.32 0.12 0.86
Wirehaired Fox Terrier 3 0.0301 0.32 0.10 1.00
Husky 21 <0.0001 0.29 0.19 0.44
Bulldog 5 <0.0001