Keratoacanthoma Pathology: Histology and How It Differs From SCC

Keratoacanthoma (KA) is a fast-growing, dome-shaped skin tumor. Under the microscope it shows a crater-like (crateriform) architecture, a central plug of keratin, well-differentiated squamous cells and overhanging epithelial “lips” at the edges. The hard part of KA pathology is not describing it. It is separating it from squamous cell carcinoma (SCC), because the two share clinical and microscopic features. This guide walks through what pathologists see, which clues carry the most weight, why the biopsy itself matters, and how Spitz nevus histology compares, since readers often look up both lesions together.

TL;DR

• KA is a rapidly growing, crateriform skin tumor with a keratin-filled center and well-differentiated squamous cells. It often regresses on its own over months, according to a 2024 review.
• Pathologists separate KA from SCC mainly by architecture: symmetry, epithelial lipping and where the atypia sits. No single stain settles it.
• A partial biopsy can miss the architecture that makes the diagnosis, so the sample matters as much as the slide reading.
• A Spitz nevus shows nests of spindle and epithelioid melanocytes, maturation with depth and pink Kamino bodies. Borderline cases may need molecular testing.
• Any fast-growing skin lesion needs a clinician’s exam and tissue diagnosis. Do not wait for it to “go away” on its own.

Table of Contents

• What keratoacanthoma is
• Keratoacanthoma histology: what the pathologist sees
• Keratoacanthoma vs. squamous cell carcinoma
• Why the biopsy matters as much as the slide
• Spitz nevus histology and pathology
• KA and Spitz nevus side by side
• Perspective: why subspecialty reading matters here
• What to do if you have a fast-growing lesion
• For clinicians: getting the most from a dermatopathology read
• Working with EIV Diagnostics
• FAQ
• Sources

What keratoacanthoma is

KA is a skin tumor that typically arises on sun-exposed skin and grows quickly, over weeks to months. A 2024 academic review describes it as dome-shaped with a central keratin plug, and notes that it typically grows fast and then spontaneously regresses. The same literature describes regression over roughly four to six months in most cases, which is the textbook behavior that separates it from a typical cancer.

That textbook behavior is also the source of the controversy. Some pathologists treat KA as its own benign entity. Others regard it as a well-differentiated variant of squamous cell carcinoma, sometimes labeled SCC, KA type. A Japanese study asking what a solitary keratoacanthoma actually is frames it as a follicular lesion with benign features. Both views exist in the literature, and that is why the pathology report wording matters so much.

Because nobody can tell at the bedside whether a rapidly growing bump will regress, the safe path is a biopsy and a pathologist’s reading, not observation alone.

Keratoacanthoma histology: what the pathologist sees

A pathologist reads KA at two levels: the low-power “shape” of the lesion and the high-power look at individual cells. The shape usually carries more of the diagnosis.

Low-power architecture

At low magnification, KA is described as exo-endophytic and crateriform. In plain terms:

• Crater shape. The lesion rises above the skin and also pushes down into it, forming a cup.
• Central keratin plug. The crater is filled with keratin, the same protein that makes up the outer skin layer.
• Epithelial lips. The edges of normal-looking epithelium extend over the sides of the crater like a lip or buttress.
• Symmetry. The silhouette is typically balanced from one side to the other.

These features are listed in the 2024 review comparing KA with squamous cell carcinoma, and they are why the review stresses that architecture is often more important than cytology alone.

High-power cytology

Up close, the cells are well-differentiated squamous cells. The Japanese study describes enlarged, pale pink cells with ground-glass-like cytoplasm, and notes that KA typically lacks nuclear atypia. Mild pleomorphism, meaning some variation in cell size and shape, can appear, especially at the periphery. Mitoses can be present. Neither of these alone makes it cancer, which is exactly the trap.

A note on timing

KA changes with time. Early lesions may look more like a growing nodule with less crater. Mature lesions show the classic cup with a keratin plug. Regressing lesions can show inflammation and fibrosis. The stage at which the biopsy was taken therefore shapes what the pathologist can see, and a good clinical history (how long the lesion has been growing, how fast, and where) helps the reading.

Keratoacanthoma vs. squamous cell carcinoma

This is the question behind most searches for KA pathology. The honest answer is that the two overlap. The 2024 review says that distinguishing them is difficult because of shared clinical and histopathologic features, and that this is why some label KA a well-differentiated SCC of the KA type.

What pathologists weigh, according to that review:

Two cautions come with this table. First, these are tendencies, not rules. Second, the same review states that no single immunohistochemistry (IHC) stain definitively distinguishes KA from SCC. IHC can help narrow an ambiguous case, but the diagnosis still rests on putting architecture, cytology, stain patterns and the clinical story together.

Why the follicular question comes up

People also ask what follicular squamous cell carcinoma is. In this context it is the name some authors use for lesions arising from the hair follicle epithelium, which is where KA is thought to originate according to the Japanese study above. That shared origin helps explain why the two look so alike.

Why the biopsy matters as much as the slide

The 2024 review identifies inadequate sampling as a major diagnostic pitfall. If a shave or small partial biopsy captures only a piece of the lesion, for example just the keratin plug or one edge, the pathologist cannot see the symmetry, the lips or the base. Since architectural features count more than cytology alone, a fragment can look like SCC when the whole lesion would have read as KA, or the reverse.

The review states that complete excision is preferred. For clinicians, that means a few practical habits:

1. Sample the whole lesion when feasible, including the edge and the base, rather than the top only.
2. Put the clinical details on the requisition: duration of growth, rate, size, location, prior sun damage or immune status.
3. If the first sample is limited and the report is hedged, discuss a re-sample or excision with the pathologist instead of treating the hedge as a final answer.

Our own guide on skin biopsy types and how to avoid repeat biopsies covers the choices clinicians face at the bedside.

Other lesions that can confuse the picture

Fast-growing, crusted or crater-like bumps are not always KA or SCC. On the lip, for instance, a benign fluid-filled lesion such as a mucocele on the lip can be mistaken for something more worrying, and the reverse also happens. That is one reason a lesion that is not clearly fading within a few weeks deserves a clinician’s look rather than a guess.

Spitz nevus histology and pathology

Many readers searching for KA also look up Spitz nevus, because both are lesions that can alarm patients and sit near a cancer diagnosis in the differential. They are different in kind: KA is an epithelial (squamous) tumor, while a Spitz nevus is a melanocytic lesion, meaning it arises from pigment-producing cells.

According to a 2022 review of Spitz melanocytic lesions, a classic Spitz nevus is characterized by:

• nests of spindle-shaped and epithelioid melanocytes;
• maturation with depth, meaning the cells get smaller and more nevus-like as they go deeper into the skin;
• Kamino bodies, which are pink, eosinophilic hyaline globules.

Spitz nevus vs. atypical Spitz tumor vs. spitzoid melanoma

The same review describes a spectrum. A benign Spitz nevus sits at one end, spitzoid (Spitz) melanoma at the other, and the atypical Spitz tumor (AST) in between. Pathologists look for high-risk features:

• asymmetry and poor circumscription;
• large size;
• ulceration;
• lack of maturation with depth;
• a high mitotic rate (more than 6 per mm²);
• atypical or deep mitoses.

Because these features overlap, the review says molecular testing is critical for definitive classification. It looks for kinase fusions, CDKN2A loss and specific mutations. That is a very different tool from the one used in KA, where architecture leads and IHC offers partial help. If you want to understand what such testing detects, see our overview of molecular pathology tests and how they work and what molecular cancer testing results mean for treatment.

If a report mentions Breslow depth or ulceration after a melanoma diagnosis, our walkthrough of the melanoma pathology report explains the terms.

KA and Spitz nevus side by side

Perspective: why subspecialty reading matters here

We see KA and Spitz lesions as two examples of the same lesson: the slide is only as good as the sample and the person reading it.

Neither diagnosis comes down to one dramatic feature. KA depends on seeing the whole silhouette, the crater, the lips and the balance of the lesion. Spitz lesions depend on weighing several high-risk features together and, when they conflict, bringing molecular data to the table. That kind of judgment is why we built EIV Diagnostics around board-certified pathologists with subspecialty expertise, supported by digital and molecular diagnostic technology.

Our position is simple. When a lesion sits on the line between benign and malignant, the clinician and the patient are better served by a careful, complete reading than by a fast, thin one. Rapid turnaround matters, and so does a report that clearly states what was seen and what remains uncertain, so the treating clinician can decide on the next step.

EIV Diagnostics

What to do if you have a fast-growing lesion

If you are a patient, the practical points are short.

• Do not wait it out. KA often regresses, but a fast-growing bump cannot be told apart from SCC by eye. A clinician should examine it, and tissue diagnosis settles the question.
• Ask about the type of biopsy. A sample that captures the full lesion gives the pathologist more to work with.
• Ask for the report in plain words. If it says SCC, KA type, or “cannot exclude,” ask your clinician what that means for treatment.
• Sun protection and skin checks. Both KA and SCC are linked to sun-damaged skin, so a regular skin exam with a dermatologist is sensible.

If your report leaves you with questions about next steps, our guide to what to expect after a skin cancer diagnosis may help, and our piece on basal cell testing and the biopsy methods that confirm a diagnosis explains how tissue is collected.

For clinicians: getting the most from a dermatopathology read

For physicians sending skin specimens, a few steps raise the odds of a definitive report:

1. Send adequate tissue. For a suspected KA, aim to include the center and the margins of the lesion so the architecture can be assessed.
2. Give the clinical story. Rapid growth over weeks, a crateriform look, location and patient risk factors all belong on the requisition.
3. Ask about ancillary testing early. For ambiguous KA/SCC cases, IHC may help but is not definitive. For Spitzoid lesions, discuss whether molecular testing is appropriate.
4. Close the loop. If the pathologist recommends re-excision or additional sampling, document it and tell the patient why.

Our dermatopathology service is built for this kind of work, and our digital pathology and molecular pathology services support the harder calls. If you want to know how confocal imaging fits into skin cancer workups, read our article on confocal microscopy for melanoma.

Working with EIV Diagnostics

EIV Diagnostics is an independent pathology laboratory in Fresno, California. We serve physicians, patients with prescriptions and self-pay customers across the Fresno, Clovis, Madera, Visalia and wider Central Valley area. Our pathologists are board-certified, our lab is CAP-accredited, and our services include dermatopathology, histopathology, cytology, molecular pathology and digital pathology.

If you need lab work done without a trip to a lab, our mobile phlebotomy service comes to your home or office, starting from $65. Patients who want to order tests without a doctor’s visit can learn more on our self-pay testing page. Clinicians can see the full list on our services page.

FAQ

How common is keratoacanthoma?

KA is considered a relatively common skin tumor, and it most often appears on sun-exposed skin of older adults. Exact rates differ between studies, partly because pathologists do not all classify KA the same way. If you have a lesion that fits the description, a clinician’s exam is the way to find out what it is.

What are the histological features of keratoacanthoma?

The classic picture is a symmetric, crateriform lesion with a central keratin plug, overhanging epithelial lips and well-differentiated squamous cells with pale pink, ground-glass-like cytoplasm. Nuclear atypia is typically absent or mild. Pathologists lean on architecture more than on cell detail.

Is keratoacanthoma painful?

KA is usually described as a firm, fast-growing nodule, and many are painless, though some are tender. Pain or bleeding does not tell you whether a lesion is KA or SCC. Any fast-growing bump should be examined by a dermatologist or other clinician, and a biopsy decides the diagnosis.

What does Spitz nevus look like under the microscope?

A Spitz nevus shows nests of spindle and epithelioid melanocytes that mature with depth, often with pink Kamino bodies. When features such as asymmetry, ulceration, lack of maturation or deep mitoses appear, pathologists consider an atypical Spitz tumor or spitzoid melanoma, and molecular testing may be used to classify the lesion.

Can a stain prove keratoacanthoma instead of squamous cell carcinoma?

No. Patterns such as basal Ki-67 and central CK17 staining support KA, while diffuse Ki-67 favors SCC, but no single stain is definitive. The final call combines architecture, cytology, stains and the clinical history.

Sources

• Keratoacanthoma versus Squamous-Cell Carcinoma (2024 review)
• What Is a Solitary Keratoacanthoma? A Benign Follicular Tumor
• The Spectrum of Spitz Melanocytic Lesions: From Morphologic Diagnosis to Molecular Classification

Recommended

• Dermatopathology Services
• Histopathology Services
• Basal Cell Testing: 4 Biopsy Methods Confirming Diagnosis for Patients
• Skin Cancer Diagnosis: What to Expect and Next Steps