Introduction

What is pyoderma gangrenosum?

Pyoderma Gangrenosum (often shortened to PG) is a rare condition that leads to the formation of painful ulcers and sores on the skin, most commonly the legs. While PG is often assumed to be an immune disorder, the exact cause remains unknown, individuals with other underlying conditions can be at a higher risk of developing PG, such as those with inflammatory bowel disease (IBD).¹

What is the purpose of studying histopathology?

Histopathology involves the diagnosis of diseased tissue through the study of cells and/or tissues under a microscope. When examining samples, histopathologists look for specific or abnormal cells, or cell behaviour that may indicate the presence of a disease. 

In addition, histopathology can be used to rule out diseases and diagnose them, which helps narrow the potential scope of the diagnosis as early as possible. 

Histopathologists often work closely with other clinical specialists to achieve a correct and timely diagnosis, making their role crucial in maximising many patients’ chances of treatment and recovery.

Overview of histopathology in PG

Due to the cause of PG remaining mostly unknown, histopathology is used to eliminate several more common diseases, helping to narrow down the possibilities until the correct diagnosis is reached. Often, histopathology is used alongside additional clinical findings, such as relevant patient history, the presence and severity of ulcers, and associated systemic diseases.²

Common microscopic features of PG

In a PG biopsy, one of the most common findings is an extreme neutrophilic infiltrate, which is a large number of neutrophils that are found within the lesion, indicating infection. 

Figures 1 & 2 demonstrate what this may look like under a microscope

Figure 1: histological findings showing an intense neutrophilic infiltrate, represented by the deep purple colouring resulting from staining.³

Figure 2: Histopathology of a skin lesion showing neutrophilic infiltration (left arrow).⁴

Additionally, upon histological examination, many patients exhibit vasculitis, leading to the inflammation and swelling of blood vessels. 

In one observational study, patients with neutrophillic infiltrates examined with PG also presented with vasculitis. ⁵.

Variability in histological appearance

While there are common histological features to aid in the diagnosis of PG, its appearance under a microscope can vary depending on multiple factors. For example, early lesions (seen as less severe) will present with neutrophilic infiltrates, but will likely lack other complications. However, late lesions (more severe) will often display tissue necrosis (death) due to prolonged damage and infection.

Differential diagnosis

As PG is normally diagnosed through the process of elimination, there are a number of alternative diseases that may appear similar to PG, potentially leading to an incorrect diagnosis. One study found that misdiagnosis of PG can reach a frequency of 10%, and concluded that six disease categories may simulate PG. 

These include:⁶ 

• Venous disease
• Vasculitis
• Cancer
• Infection
• Exogenous tissue injury
• Inflammatory disorders

Despite being relatively common, the misdiagnosis of PG may have a crucial impact on patient’s recovery and health. 

One study perfromed in 2018, describes a case where PG was initially misdiagnosed as a more common infection. 

Importance of clinicopathological correlation

Having looked at the histopathology and microscopic features that help to diagnose PG, it is now important to emphasise that PG must never be diagnosed based solely on histological findings. As mentioned above, there are numerous diseases which can appear identical to PG under a microscope, and therefore it is essential that other clinical factors are used to eliminate the possibility of more common diseases before settling for a diagnosis of PG.

As highlighted by a study conducted in 2022, the identification of specific morphological characteristics can aid in the diagnosis of more uncommon types of PG. This exemplifies the need to integrate clinical context when examining the evidence for diagnosis, distinguishing PG from other similar conditions.⁸

The use of histopathology in PG is primarily to exclude the possibility of other causes, not to find a definitive diagnosis. In many cases, clinicians may rush to diagnose an individual with a more common condition, such as cancer, without examining alternative clinical features in more detail.

FAQs

How is PG treated?

PG is usually managed through the administration of immunosuppressive drugs and corticosteroids, and usually remains non-surgical.⁹

What can cause PG?

PG is usually caused by dysfunctional neutrophils, infiltrating areas of the skin. Common triggers include injury to the skin and occasionally drug misuse.⁹

Summary

Throughout this article, it has been made evident that the rare disease pyoderma gangrenosum (PG) poses multiple challenges during diagnosis. With no distinct histopathological feature that is present only in PG, diagnosis involves using histology to rule out other potential diseases. 

While a biopsy remains important, other clinical features of PG should be identified to support an accurate diagnosis, facilitating the best possible treatment for a patient. Histology remains useful for ruling out many types of infections and cancers, but accurate diagnosis requires a much more multifaceted approach.