Pseudoepitheliomatous Hyperplasia: a Word of Caution

Published: 2021-09-13 20:40:09
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Category: Human Body, Illness

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Pseudoepitheliomatous hyperplasia (PEH) is a benign skin condition associated with a wide variety of disease, including cancer. The diagnosis is based upon histologic characteristics and thus requires a formal biopsy. Due to its ambiguity, particularly the range of other conditions in which it is associated, a report of PEH instills much difficultly upon the receiving clinician, especially if malignancy had not been discounted prior to the biopsy. If one finds themselves in such a situation when caring for a patient, due diligence is warranted. Determining whether or not additional studies are appropriate should not be taken lightly with a diagnosis of PEH, as the decision may result in significant consequences.
Keywords: Pseudoepitheliomatous hyperplasia; Squamous cell carcinoma; Benign; Malignant Abbreviations PEH: pseudoepitheliomatous hyperplasia SCC: squamous cell carcinoma HS: hidradenitis suppurativaIntroduction
Pseudoepitheliomatous hyperplasia (PEH) is a benign skin disease associated with reactivity to chronic inflammation. The variety of disease in which pathologic inflammation occurs is vast. As such, PEH has been associated with many different conditions ranging from infectious to non-infectious, benign to malignant. Occult infections and autoimmune disorders are among the most common pathologic entities associated with PEH. Peculiar reactions to foreign bodies have also been reported, including tattoo ink. However, despite the benign nature of these diseases, PEH has also been associated with many forms of malignancy, including melanoma. The ambiguity that materializes from a report of PEH presents the receiving clinician with significant challenge, especially if the clinical picture had been previously unclear. With a diagnosis of PEH, consideration for its many associated conditions, along with tenacious clinical judgement, is required when weighing the risks versus benefits in regard to attempting further diagnostics. We present a case that highlights this principle.
Case Presentation
A 56-year-old Caucasian woman presented with increasingly severe pain and drainage secondary to a chronic perineal wound of approximately three years’ duration. She also reported recently discovering a new “bump” in her vagina. Several biopsies of her wound taken over the previous two years had reported PEH. However, all subsequent attempts to reveal an occult infection were unsuccessful. Her past medical history included psoriasis and hypothyroidism; she had no history of malignancy, immunocompromise, nor Crohn’s disease. There was no history of cancer in her family. Upon examining the patient, a circumscribed area of induration and erythema could be visualized just left of the perineum. Due to uncontrolled pain, a pelvic exam was deferred at that time, and the patient elected for a pelvic exam under anesthesia with additional biopsies. In the operating room, a small nodule was palpated in the anterior vaginal wall. Excisional biopsies were taken of both the vaginal nodule and perineal wound. The perineal wound biopsy reported squamous cell carcinoma (SCC) in a background of hidradenitis suppurativa (HS). The biopsy of the vaginal nodule returned as melanoma with lymphovascular invasion. The patient underwent a PET scan which reported metastatic intrathoracic, retroperitoneal, and pelvic lymphadenopathy. A subsequent retroperitoneal lymph node biopsy confirmed metastatic melanoma.
PEH is a benign skin condition associated with a variety of ongoing inflammatory states such as those seen with chronic infection and autoimmune disorders. PEH has also been associated with many malignancies, including melanoma. HS is a chronic inflammatory disease that affects areas of the skin containing apocrine glands, such as the groin and axillae. In addition to its deleterious effects on patient self-esteem and quality of life, HS is also associated with SCC. It is well known that SCC can arise with chronic inflammation, also known as a Marjolin’s ulcer. As such, the association between a chronic inflammatory condition such as HS with SCC is not unexpected. However, the association between PEH and melanoma may be less well known. Furthermore, to our knowledge, there have been no reports of these two processes occurring simultaneously in the same patient. Given the potential for devastating consequences that may arise from such diagnoses, clinicians must exhibit proper judgement when faced with a report of PEH.
Although PEH remains a benign condition in and of itself, some authors believe it may take place on a spectrum of transformation from benign to malignant. Even still, others warn of potential iatrogenesis that may occur as a result of unnecessary attempts at differentiating PEH from true oncologic processes. Of additional concern is the opportunity for false positives, especially given that differentiating PEH from SCC appears rather difficult. When the difficultly in differentiating between these two diseases is considered with the disparity of their prognoses, the pressure of making the right clinical decision becomes apparent. Although factors such as membrane invasion may help in determining malignant potential, proper biopsies to assess for such characteristics may result in significant scaring or prove difficult to obtain by standard procedures.
There is an apparent risk of obtaining invasive biopsies only to discover that they were unnecessary due to benign disease. Thus, the true difficultly in differentiating PEH from SCC exist within not only making the decision of whether further biopsies are indicated, but how they can be obtained appropriately and with adequate yield, as well. When a patient has a skin lesion of unknown etiology, physicians are trained to consider the entire clinical picture. For most physicians, their medical training has resulted in a low-threshold for initial biopsies.
Despite the routineness in decision making up until this point, many welltrained physicians may not feel as comfortable after receiving reports of PEH. Before discounting the news of this benign entity, clinicians should remain mindful of its associated conditions. Watchful waiting with further biopsies reporting continued PEH, especially with concomitant dysplasia and/or atypia, should signal warning signs that necessitate more aggressive management. Judgement should not be abandoned, however, as chasing after benign disease will only result in unnecessary diagnostics. Moreover, the squamous hyperplasia seen in PEH requires caution in order to avoid unnecessary iatrogenesis that may follow a false positive diagnosis of SCC. Nonetheless, the potential for missed opportunities in early recognition and thus more favorable outcomes must be considered when weighing the risks versus benefits of obtaining further studies, especially when pretest probabilities are high. In any case, with a diagnosis of PEH, proper and adequate clinical judgement is paramount when deciding whether or not further biopsies are warranted.

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