Novel Histopathological Findings of Micro Bone Fragments and Epithelial Response in the Oral Mucosa in Bisphosphonate-Related Osteonecrosis of the Jaw.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) occurs in the jawbone and interfacing oral mucosa of patients treated with bisphosphonates. Herein, we report novel histopathological findings in the oral mucosa of a surgical specimen obtained from a 61-year-old man with BRONJ. The resected jawbone and adjacent oral mucosa were separated for histological examination. The mucosal tissue was examined using Von Kossa staining and immunohistochemical (CK5/6, p63) staining of non-decalcified paraffin sections. Pseudoepitheliomatous hyperplasia (PEH), a microscopic feature of the mucosal epithelium in BRONJ, was observed in soft tissue specimens, concomitant with inflammatory cell infiltration. Von Kossa staining revealed small fragments of necrotic bone, tens to hundreds of micrometers in size, scattered within the connective tissues; the PEH forefront contacted some of the bone fragments. Immunohistochemical staining demonstrated that occasionally, the PEH not only contacted but also encompassed the bone fragments. To our knowledge, this is the first report of presence of micro bone fragments and their association with PEH in the oral mucosa in BRONJ.

Ocular surface squamous neoplasia masquerading as pseudoepitheliomatous hyperplasia in chronic vernal keratoconjunctivitis.

We report a rare case of ocular surface squamous neoplasia (OSSN) masquerading as pseudoepitheliomatous hyperplasia in chronic vernal keratoconjunctivitis (VKC). A 24-year-old man presented with a history of bilateral VKC since childhood with a superior limbal mass in the right eye. There was a history of use of intermittent corticosteroids in the past. He underwent impression cytology followed by excision biopsy with wide margins (no touch technique), cryotherapy and amniotic membrane transplantation. Histopathological analysis confirmed the diagnosis of OSSN with mild to moderate dysplasia. This case highlights the importance of strong clinical suspicion and detailed cytological and histopathological examination for early detection and management of OSSN.

Cutaneous Squamous Cell Carcinoma Mimickers: Beware the Pruritic Papule on the Leg of an Older Female.

Background Correctly identifying cutaneous squamous cell carcinoma (cSCC) mimickers can be both clinically and histopathologically challenging. We present a series of patients with biopsy-proven cSCCs for whom multiple surgeries were avoided by assessing the clinical situation, recognizing an alternative diagnosis that pathologically mimics cSCC, and prescribing appropriate therapy for the underlying condition. Methodology Seven female patients presented for treatment of biopsy-proven cSCC affecting the lower leg. After further investigation, we observed that these women shared similar characteristics, including age ranging from the 5th to the 9th decade, often experiencing stress, exhibiting associated pruritus with diverse causes, having few or no previous skin cancers, and generally showing minimal photodamage. Results In all cases, surgery was deferred and patients demonstrated complete clinical response to therapies directed toward an alternative diagnosis. Repeat biopsies of treated lesions revealed no evidence of cSCC. Conclusions Not all histologically diagnosed cases of cSCC should be treated with surgery, and each patient should be worked up thoroughly to evaluate for an alternative diagnosis. Possible clinical and histologic cSCC mimickers include allergic contact dermatitis (ACD), stasis dermatitis, hypertrophic lichen planus (LP), and drug eruption, among others. In the described population, pruritic papules on the lower leg should prompt further investigation to prevent the morbidity associated with unnecessary surgery.

Perforating Gout: Expanding the Differential for Transepidermal Elimination.

Perforating dermatoses are dermatologic disorders with transepidermal elimination (TE) of dermal substances. While TE is typically associated with collagen and elastin, it can also occur as a secondary event in other processes, and it is important to keep a broad differential. We present a case of perforating tophaceous gout, which underscores the need for a thoughtful approach to perforating disorders. An updated review of recent literature is also presented.

Peristomal Pseudoverrucous Lesions: A Rare Skin Complication of Colostomy.

A 56-year-old female patient with colostomy presented with skin-colored cobblestone and verrucous asymptomatic papules on her peristomal skin for three months; she was referred to dermatology. Histopathology revealed irregular acanthosis, tongue-like extension of rete ridges of mature squamous epithelium without atypical morphology, hyperkeratosis, and inflammation of the skin. The histopathologic appearance was evaluated as compatible with pseudoepitheliomatous hyperplasia. No signs of malignancy, fungus, or koilocytes were found. The lesions were diagnosed as pseudoepitheliomatous hyperplasia by clinical and histopathologic findings. In this case report, we review pseudoepitheliomatous hyperplasia associated with colostomy.

Pathogenesis, Diagnosis and Management of Squamous Cell Carcinoma and Pseudoepithelial Hyperplasia Secondary to Red Ink Tattoo: A Case Series and Review.

The increasing popularity of tattooing has paralleled an increase in associated cutaneous reactions. Red ink is notorious for eliciting cutaneous reactions. A common reaction is pseudoepitheliomatous hyperplasia (PEH), which is a benign condition closely simulating squamous cell carcinoma (SCC). Differentiating PEH from SCC is challenging for pathologists and clinicians alike. The exact pathogenesis of these lesions secondary to red ink is not known, and there are no sources outlining diagnostic and treatment options and their efficacy. We present four study cases with different pathologies associated to red ink tattoos including lichenoid reaction, granulomatous reaction, PEH, and an SCC. Additionally, an extensive review of 63 articles was performed to investigate pathogenesis, diagnostic approaches, and treatment options. Hypotheses surrounding pathogenesis include but are not limited to the carcinogenic components of pigments, their reaction with UV and the traumatic process of tattooing. Pathogenesis seems to be multifactorial. Full-thickness biopsies with follow-up is the recommended diagnostic approach. There is no evidence of a single universally successful treatment for PEH. Low-dose steroids are usually tried following a step up in lack of clinical response. For SCC lesions, full surgical excision is widely used. A focus on clinicians' awareness of adverse reactions is key for prevention. Regulation of the unmonitored tattoo industry remains an ongoing problem.

Nasal Extranodal Natural Killer/T-cell Lymphoma Imitating Squamous Cell Carcinoma: A Case Report.

Nasal extranodal NK/T-cell lymphoma (NNKTL) is a lethal disease due to poor prognosis with rapid progress. A 56-year-old man complained of left nasal obstruction and blood-stained nasal drip for two months. Incisional biopsies were performed at the outpatient department three times, and the diagnosis of SCC was made. The patient underwent wide excision of the entire lesion via endoscopic sinus surgery with navigation. Final pathologic report revealed NNKTL. Pathological examination of the tumor revealed overlying epithelium presenting as pseudoepitheliomatous hyperplasia (PEH), which mimicked SCC invasion, with infiltration of atypical lymphocytes in the deeper sections. Immunohistochemistry supported the diagnosis of NNKTL. Chemoradiotherapy was administered, and a complete response was achieved at the two-year follow-up. The correct diagnosis of NNKTL is essential for prompt treatment and prevention of superfluous surgery. Although the link between PEH and NNKTL may lead to a misdiagnosis of SCC, multiple large and deep biopsies can prevent this dilemma. A biopsy showing ulceration or necrosis can indicate PEH and imply potential malignancy. Repeated biopsies and complete immunohistochemical studies are important for diagnosing NNKTL.

Blastomycosis-like pyoderma: A pitfall for the misdiagnosis of squamous cell carcinoma.

Blastomycosis-like pyoderma is a rare cutaneous disease presenting as solitary or multiple verrucous or ulcerated plaques and nodules in a susceptible patient. The diagnostic criteria include characteristic verrucous plaques with pustules and elevated borders, histopathologic findings of pseudoepitheliomatous hyperplasia with abscesses, growth of at least one bacterium in tissue culture, and exclusion of other infectious sources. This report describes a case of a 62-year-old man with poorly controlled type 2 diabetes mellitus who presented with plaques, nodules, and ulcers in both groins and the right ankle. The patient was initially misdiagnosed with multiple squamous cell carcinomas and underwent several operations. A review of the pathology slides revealed pseudoepitheliomatous hyperplasia with multiple dermal abscesses, while repeated wound and tissue cultures were positive for coagulase-negative Staphylococcus. Blastomycosis-like pyoderma was diagnosed. The patient was subsequently treated with culture-guided prolonged antibiotic therapy followed by intralesional steroid injection, which led to gradual resolution of the lesions.

Disoriented collagen fibers and disorganized, fibrotic orbicularis oris muscle fiber with mitochondrial myopathy in non-syndromic cleft lip.

OBJECTIVE: This study aims to explore and compare the histopathology of upper cleft lip tissue in order to identify the abnormalities and orientation of muscle and collagen fibers in patients affected with non-syndromic cleft lip with or without cleft palate (NSCL±P) and normal controls. MATERIALS AND METHODS: Eight fresh lip tissues of consented patients with NSCL±P and two controls were fixed and stained with hematoxylin and eosin (H&E), Masson's trichrome (MT), and modified Gomori trichrome techniques. The images were captured and examined using imaging cellSens software (Olympus, Tokyo, Japan) and Mirax Scan (Carl Zeiss, Germany). The H&E stained tissues were analysed for muscle fiber size using image processing program (imageJ, USA). Histopathological appearance of epidermal and dermal layers including collagen orientation, as well as muscle fibers abnormalities were observed. RESULTS: Tissues stained with H&E exhibit pseudoepitheliomatous hyperplasia, epidermal and sebaceous glands hyperplasia. Morphometric analysis of muscle fibers showed the diameter was between 6.912 and 10.246 µm. Collagen fibers were densely packed in cleft tissue, but muscle fibers were sparse in MT stain. Modified Gomori trichrome stain revealed hypoplastic muscle with fibrosis, including ragged red fibers. CONCLUSION: Disoriented collagen fibers, significant sparse and disorganized orbicularis oris muscle fibers with classical myopathic appearances proved that cleft tissue had abnormal histology findings. These findings further support the mechanism of collagen and muscle fibers during embryonic development that causing cleft formation.

Pseudoepitheliomatous hyperplasia of the auricle: two case reports and experiences of reconstruction.

BACKGROUND: It is rare to find pseudoepitheliomatous hyperplasia (PEH) on the auricle. PEH should be differentiated from squamous cell carcinoma (SCC). Diagnosis is made after surgery as a biopsy is often inconclusive. A free or pedicled skin flap is needed to avoid deformation of the auricle. METHODS: Adjacent pedicled skin flap is a good option for reconstruction. Moreover, it was shown how to repair the wound in the following two cases. RESULTS: The flaps grew well after surgery, and the wound healed well. CONCLUSION: PEH is a benign lesion. Adjacent pedicled skin flap is a good option for reconstruction, which can avoid deformation of the auricle.

Acyclovir-Resistant Anogenital Herpes Simplex Virus in an HIV Patient With Pseudoepitheliomatous Hyperplasia Resembling Squamous Cell Carcinoma.

Background: Herpes simplex virus (HSV) is a common infection. However, it may present atypically when patients are immunocompromised, such as with slowly expanding, long-lasting ulcerative or hypertrophic lesions. The histopathologic finding of pseudoepitheliomatous hyperplasia (PEH) can occur in a variety of situations where there is chronic inflammation and can be seen in patients with chronic HSV. Atypical presentations of HSV, particularly hypertrophic lesions with histopathologic findings of PEH, can be misinterpreted as squamous cell carcinoma, create difficulty in diagnosis and hinder appropriate treatment. Case Description: We report a case of a 59-year-old female with a past medical history of human immunodeficiency virus (HIV), who presented at a dermatology clinic with multiple exophytic ulcerations of varying sizes in the perianal region. The patient was diagnosed with HSV and was started on valacyclovir. Over a several-year period, the patient had multiple recurrences of her HSV lesions with persistent vulvodynia despite prophylactic treatment with valacyclovir. Specimens were collected for culture and sensitivities, which revealed acyclovir resistance. The patient's lesions were biopsied due to concern for possible malignancy. Biopsies revealed prominent PEH. The patient had improvement of her HSV with saucerization, topical imiquimod, and increased doses of prophylactic valacyclovir. Conclusion: Atypical, chronic presentations of HSV are common in immunocompromised patients. Hypertrophic HSV is the least common clinical presentation and can be mistaken for squamous cell carcinoma, creating difficulty in diagnosis. Due to concerns for malignancy, our patient's lesions were biopsied, which revealed prominent PEH. While PEH is benign, it can be misdiagnosed as squamous cell carcinoma on histopathology, particularly when there is clinical suspicion for malignancy. In these cases, the clinician needs to alert the pathologist to the immunosuppressed status of the patient. Detailed evaluation for infectious causes, such as HSV, can avoid misinterpretation and potential surgical and oncological overtreatment.

Unusual non-trophic ulcerations in leprosy: A case series of 17 patients.

Non-neuropathic ulcers in leprosy patients are infrequently seen, and atypical presentations are prone to misdiagnosis. We evaluated diagnosed cases of leprosy between January 2017 and January 2020 for the presence of cutaneous ulceration, Ridley-Jopling subtype of leprosy, reactions and histologic features of these ulcerations. Treatment was given as WHO recommended multi-bacillary multi-drug therapy. We found 17/386 leprosy patients with non-neuropathic ulcers. We describe three causes - spontaneous cutaneous ulceration in lepromatous leprosy (one nodular and one diffuse), lepra reactions (five patients with type 1; nine with type 2, further categorised into ulcerated Sweet syndrome-like who also had pseudoepitheliomatous hyperplasia, pustulo-necrotic and necrotic erythema nodosum leprosum) and Lucio phenomenon (one patient). Our series draws attention towards the different faces of non-neuropathic ulcers in leprosy, including some atypical and novel presentations.

Squamous Cell Proliferation as a Reactive Mechanism to Laryngeal Cryptococcus Infection: A Case Report.

Cryptococcus neoformans (C. neoformans) is a ubiquitous encapsulated, obligate anaerobe, a dimorphic fungus that can be pathogenic in humans. C. neoformans infections arise primarily in immunocompromised individuals, such as human immunodeficiency virus (HIV) patients, as well as those who use inhaled corticosteroids regularly. Due to the wide variety of clinical findings associated with C. neoformans, infection within the head and neck is occasionally misdiagnosed as malignancy due to its protean manifestation. In this report, we describe the case of a C. neoformans infection resulting in an initial misdiagnosis due to an overlying laryngeal squamous cell proliferation mimicking laryngeal squamous cell carcinoma (SCC). This case is intended to provide further evidence for inhaled corticosteroid use predisposing patients to fungal infections, as well as to provide insight into the possible mechanism resulting in the initial diagnosis of malignancy. A review of recent literature is also discussed.

Anterior segment optical coherence tomography features of pseudoepitheliomatous hyperplasia of the ocular surface: a study of 9 lesions.

PURPOSE: To describe anterior segment optical coherence tomography (AS-OCT) features of pseudoepitheliomatous hyperplasia (PEH) of the ocular surface. METHODS: This is a retrospective study of 9 lesions of 8 patients with histopathologically proven PEH RESULTS: Mean age at diagnosis of PEH was 31 years (median 31 years; range 12 to 62 years). The lesion was unilateral in 7 (88%) patients and bilateral in one (12%). Two patients (25%) had xeroderma pigmentosum, who also had a history of prior surgical intervention in the same eye for conjunctival tumor excision. Referral diagnosis was ocular surface squamous neoplasia (OSSN) in all cases. Ocular surface mass (n = 4, 44%) was the most common presenting complaint. The mean duration of symptoms was 18 months (median 3 months; range < 1 to 84 months). All lesions were perilimbal, and the mean basal diameter of the tumor was 7 mm (median 6 mm; range 4 to 12 mm). Clinical diagnosis included OSSN (n = 5; 56%), PEH (n = 3; 33%), or leiomyosarcoma (n = 1; 11%). AS-OCT features included irregular hyperreflective epithelium, epithelial dipping, and subepithelial hyperreflective lesion with posterior shadowing in all cases. Histopathology confirmed the diagnosis of PEH in all cases. The underlying cause of PEH in these cases included vernal keratoconjunctivitis (n = 4; 44%), idiopathic severe blepharitis (n = 2; 22%), or prior surgical intervention (n = 2; 22%). No apparent cause could be determined in one eye (11%). CONCLUSION: Ocular surface PEH is a close mimicker of OSSN. Careful history-taking, clinical examination, and characteristic AS-OCT features aid in accurate diagnosis.

Etiology and Management of Peristomal Pseudoepitheliomatous Hyperplasia.

This is a report of a 48-year-old male patient who presented with worsening peristomal dermatitis. He proceeded to form a nodular hyperplastic overgrowth that was proven to be pseudoepitheliomatous hyperplasia on histological examination. On surgical exploration, he was found to have an apparent peristomal enterocutaneous fistula propagating this hyperplastic growth. This report reviews the etiology and management of peristomal complications with special attention to pseudoepitheliomatous hyperplasia.

A Single Case Report of Granular Cell Tumor of the Tongue Successfully Treated through 445 nm Diode Laser.

Oral granular cell tumor (GCT) is a relatively rare, benign lesion that can easily be misdiagnosed. Particularly, the presence of pseudoepitheliomatous hyperplasia might, in some cases, lead to the hypothesis of squamous cell carcinoma. Surgical excision is the treatment of choice. Recurrence has been reported in up to 15% of cases treated with conventional surgery. Here, we reported a case of GCT of the tongue in a young female patient, which was successfully treated through 445 nm diode laser excision. Laser surgery might reduce bleeding and postoperative pain and may be associated with more rapid healing. Particularly, the vaporization effect on remnant tissues could eliminate GCT cells on the surgical bed, thus hypothetically leading to a lower rate of recurrence. In the present case, complete healing occurred in 1 week, and no recurrence was observed after 6 months. Laser surgery also allows the possibility to obtain second intention healing. Possible laser-induced histopathological artifacts should be carefully considered.