Neurofibroma with glomus-like bodies: A novel association-Thoughts about origin.

A neurofibroma with focal glomus-like body differentiation is an unusual phenomenon recently encountered in an excision specimen from the right lateral distal forearm of a 26-year-old man. Glomus cells are modified smooth muscle cells normally present in glomus-like bodies but can also be found in glomus tumors (GT) or lesions considered in the spectrum of GT, including myopericytoma, myofibroma, and angiolipoma. Neurofibromas are peripheral nerve sheath tumors derived from the neural crest cells. While both GT and its variants and neurofibroma are thought to be derived from different cell types, there is growing evidence that glomus cells have a neural crest origin. This is based on multiple theories, with some overlapping pathways, including neural crest cell differentiation, Schwann cell reprogramming, VEGF expression, and NF1 gene biallelic inactivation. This report adds to the growing evidence of possible neural crest origin for glomus cells and would help explain finding glomus-like bodies scattered through a neurofibroma.

Two Squamomelanocytic Tumors With Dendritic Melanocytes: Thoughts About Origin.

ABSTRACT: Cutaneous malignant squamomelanocytic tumor (SMT) is a rare neoplasm comprising 2 distinct cell populations of squamous cell carcinoma and a second component of either benign or malignant melanocytes. SMT most often presents as a keratotic papule in areas of chronic sun exposure, typically on the head or neck of middle-aged and elderly-aged, White male patient populations. In recent years, there has been an increase in case reports, including a review article published in 2023, identifying a total of 37 cases published in the literature. There are only 3 reported cases in the literature with spindled or dendritic cells in the melanocytic component, as most have been of the epithelioid subtype. Despite the increasing prevalence, the origin and pathophysiology is poorly understood. We report 2 cases of SMT with dendritic melanocytes that are centered around a hair follicle, proposing the theory that these 2 distinct cell types may arise from the hair follicles.

BerEP4-Negative Basal Cell Carcinoma: An Immunophenotype Not to Forget.

ABSTRACT: Basal cell carcinoma (BCC) is the most common cancer worldwide. Although not typically metastatic, BCC can be locally destructive. BerEP4 is an antibody against CD326, an epithelial cell adhesion molecule (EpCAM) that is expressed on epithelial progenitor cells and carcinomas. BerEP4 has been reported to have a 100% positive sensitivity in basal cell carcinomas, but a much lower sensitivity for a variety of other carcinomas, including clear cell renal cell carcinoma and metastatic renal cell carcinoma. A 74-year-old woman presented with a BerEP4-negative, but anti-renal cell antibody-positive BCC, and the stark clinical implications of misdiagnosis. This case stresses the importance of considering BerEP4-negative BCC, even when other abnormal features are present.

An Unexpected Post-Egg-Free Influenza Vaccine Granulomatous Reaction.

ABSTRACT: A 53-year-old woman presented with a pruritic plaque on the left upper arm that appeared following an egg-free flu vaccine due to a history of reaction to the standard vaccine. The affected area enlarged over a several month period immediately following vaccine administration. Physical examination revealed an 8 × 4 cm coalescent pink plaque on the left upper arm. A shave biopsy of the lesion showed dermal "naked" granulomas, or granulomas with sparse lymphocytic infiltrate at the margins, as typically seen in sarcoidosis. No foreign material was seen in the granulomatous reaction, including with polarization. Special stains, including acid fast bacilli, Grocott methenamine silver, periodic acid-Schiff, and Gram, were negative for organisms. The diagnosis of granulomatous dermatitis was made. Subsequent imaging demonstrated no findings suggestive of sarcoidosis. While vaccine-associated hypersensitivity reactions occur frequently, these reactions are typically due to individual vaccine components, such as egg protein, and do not normally result in the formulation of granulomas. Vaccination-induced granulomas are more often associated with the use of aluminum as an adjuvant; however, this is not present in the egg-free influenza vaccine. Thus, a granulomatous reaction to the egg-free influenza vaccine is very unusual and, to our knowledge, not previously reported.

Chronic Radiation Dermatitis Secondary to Narrow-Band Ultraviolet B Therapy in a Patient With Primary Cutaneous CD8 + T-Cell Lymphoma With Cytotoxic Granules.

ABSTRACT: Conventional therapies for CD8 + cutaneous T-cell lymphoma include topical steroids, topical nitrogen mustard, topical bexarotene, ultraviolet B therapy, psoralen and ultraviolet A therapy, local radiotherapy, and interferon alfa; however, these treatments are often found to be ineffective. Presented is a case of CD8 + cutaneous T-cell lymphoma with near-complete response to narrow-band ultraviolet therapy because of chronic radiation dermatitis initially believed to be possible progression of a CD8 + cutaneous epidermotropic cytotoxic T-cell lymphoma.

Pseudolymphoma to Lymphoma: A Case of Chronic Reactive Lymphoid Hyperplasia Transforming to Primary Cutaneous Marginal Zone Lymphoma.

ABSTRACT: Primary cutaneous marginal zone lymphoma (PCMZL) is a low-grade malignant B-cell lymphoma that originates from the skin. It often presents as erythematous solitary or multiple papules, nodules, and/or plaques. It is one of the 3 main subtypes of primary cutaneous B-cell lymphomas. PCMZLs are believed to develop from chronic antigenic stimulation such as from tick-borne bacteria, vaccines, tattoo pigment, or other foreign body. In addition, cutaneous lymphoid hyperplasia, a documented precursor to malignant PCMZL, often presents in response to areas of chronic inflammation. Cutaneous lymphoid hyperplasia and PCMZL share several clinical and histological similarities that require clinicopathologic suspicion, immunohistochemical ancillary studies, and histopathologic analysis to accurately differentiate the 2 entities. Although gene rearrangement studies have historically been of limited value in the diagnosis of PCMZL, recent studies investigating molecular markers have identified the presence of multiple genetic abnormalities that have helped to better characterize the disease and aid in diagnosis. In addition, newer studies have found associations between PCMZL and gastrointestinal disorders, including Helicobacter pylori and inflammatory bowel disorders. In this article, we describe a case of a 56-year-old patient with a history of ulcerative colitis presenting with chronic reactive lymphoid hyperplasia that transformed to primary cutaneous marginal zone lymphoma.

Radiation-Induced Eccrine Squamous Syringometaplasia With Perineural Invasion.

ABSTRACT: Eccrine squamous syringometaplasia (ESS) is a benign metaplastic reaction of eccrine ducts that occurs in response to injury and can be a histologic mimic of squamous cell carcinoma (SCC). Reported is an 82-year-old man undergoing Mohs surgery for presumed SCC diagnosed in a field of radiation dermatitis. After 3 Mohs stages, the peculiar squamous proliferation was recognized as ESS and the procedure was aborted. Complicating the interpretation of the Mohs frozen section was the presence of perineural invasion because perineural invasion has not been previously reported to occur with ESS. The histologic features used to distinguish ESS from SCC are discussed.

Novel teprotumumab treatment of severe thyroid dermopathy; ototoxicity as an adverse side effect.

Pretibial myxedema, more generally thyroid dermopathy, results from mucopolysaccharide accumulation in the dermis, typically between the knee and dorsal foot. Thyroid dermopathy presents in Graves disease, but can occur in Hashimoto thyroiditis, primary hypothyroidism, and euthyroid patients. Treatment of thyroid eye disease with teprotumumab is established in the literature, with few case reports also showing improvement in pretibial myxedema. Reported is a 76-year-old man with thyroid eye disease and pretibial myxedema treated with teprotumumab; improvement was demonstrated in both conditions. He developed "muffled" hearing as an adverse effect, a complication not widely published in the dermatology literature. At 18 months post-treatment, his symptoms are stable without recurrence, but hypoacusis persists. Given the long-term efficacy and side-effects, dermatologists should recognize the potential benefits and risks of using teprotumumab for thyroid dermopathy. A baseline audiogram may be considered prior to therapy. Additionally, longitudinal data is needed to document the benefits and risks of this novel therapy.

Myxoid perineurioma: an entity with many mimics.

We present a case of a female patient who presented with a 0.6cm flesh-colored "rubbery" papule on the left thigh. Biopsy revealed a dermal myxoid tumor containing spindled cells, tapered nuclei, indistinct cell borders, and a large number of mast cells. The spindle cells stained negative for S100 protein and Sox10 on immunohistochemistry, excluding myxoid neurofibroma, but positive for epithelial membrane antigen (EMA), and CD34, supporting a diagnosis of myxoid perineurioma. Interestingly, the mast cells showed cytoplasmic and nuclear positivity for microphthalmia transcription factor (MiTF). The lesion was fully excised one year later with identical histopathology and ancillary immunohistochemical profile.

Lenalidomide-induced symmetrical drug-related intertriginous and flexural exanthema.

Symmetric drug-related intertriginous and flexural exanthema (SDRIFE) is a cutaneous drug reaction that presents with symmetrical erythema in the flexures. The reaction typically appears hours-to-days after drug exposure but has been reported to occur months after drug initiation. Diagnostic criteria include cutaneous reaction after exposure to a systemic drug, erythema of the gluteal region and/or V-shaped erythema of the inguinal areas, involvement of an additional intertriginous site, symmetry, and absence of systemic involvement. The rash typically presents as macular erythema. However, variations in morphology have been reported including papules, pustules, vesicles, and bullae. The histopathology of SDRIFE is non-specific and the diagnosis is made clinically. Cessation of the causative drug leads to gradual rash resolution. Beta-lactam antibiotics are the most implicated medications but case reports describe SDRIFE following monoclonal antibodies, chemotherapeutic agents, and various other medications. We present a patient with SDRIFE secondary to lenalidomide, an immunomodulatory agent. This case highlights the importance of considering SDRIFE in the differential diagnosis of patients presenting with intertriginous erythema.

Urticarial vasculitis: A potential signpost for multisystem inflammatory syndrome in children.

Multisystem inflammatory syndrome in children (MIS-C) is a rare and serious complication of Sars-Cov-2 infection. Dermatologic manifestations are present in the majority of patients. Skin lesions found in children with MIS-C are classified into four categories: morbilliform, reticulated, scarlatiniform, and urticarial lesions. Clinicopathologic characterization within these categories is limited. Thus, we present a clear example of an urticarial lesion in the context of MIS-C with well-documented clinicopathologic phenomena. A previously healthy 16-year-old female presented with 3 weeks of an itchy, burning rash initially presenting on her right forearm (and lasting greater than 24 hours without migration) before spreading diffusely. She also reported fever, cough, myalgias, nausea, and vomiting of 4 weeks' duration. Physical examination revealed an edematous, maculopapular, nonblanching, erythematous rash covering the patient's upper extremities, abdomen, back, anterior thighs, and face. The patient tested positive for COVID-19. A low-grade leukocytoclastic vasculitis was noted along with intraluminal fibrin and rare microthrombi in vessels of the mid to deep dermis. The patient was diagnosed with MIS-C and urticarial vasculitis. She was treated with steroids and naproxen for subsequent MIS-C flares. Dapsone treatment was started for the urticarial vasculitis.

Kaposi sarcoma: What to do with a negative human herpesvirus 8 immunohistochemical stain?

Kaposi sarcoma (KS) is an intermediate vascular sarcoma that can cause significant morbidity and mortality in patients if left untreated. It is associated with human herpesvirus 8 (HHV-8) infection. Definitive diagnosis is supported by classic histopathology including slit-like vascular spaces, spindle cells, lymphocyte infiltration, and extravasated red blood cells on H&E stain and positive immunohistochemical (IHC) staining for HHV-8. We present a challenge we encountered in detecting HHV-8 by IHC in a mucosal lesion demonstrating classic histopathology for KS.

Treating linear porokeratosis with topical lovastatin/cholesterol cream.

Linear porokeratosis is a rare variant of porokeratosis that is characterized by unilateral lesions along the lines of Blaschko. Like all variants of porokeratosis, linear porokeratosis is characterized by the histopathologic finding of cornoid lamellae bracketing the lesion. The underlying pathophysiology involves a two-hit post-zygotic knockdown of genes involved in mevalonate biosynthesis in embryonic keratinocytes. Although there is currently no standard or effective treatment, therapies targeted to rescue this pathway and restore keratinocyte cholesterol availability are promising. Presented here is a patient with a rare, extensive case of linear porokeratosis treated with compounded 2% lovastatin/2% cholesterol cream leading to partial resolution of the plaques.

Rare mimic of angiosarcoma: Erythema ab igne with reactive angiomatosis.

Erythema ab igne is an uncommon physical dermatosis that presents with localized patches of reticulated erythema and hyperpigmentation corresponding with the underlying dermal venous plexus. The rash occurs in response to chronic heat exposure that does not meet the threshold for thermal burn of the skin. The histopathologic findings are characterized by atrophy and thinning of the epidermis, focal hyperkeratosis, and keratinocyte atypia. The dermis displays dilated capillaries, evidence of pigment incontinence, and prominent elastotic material. We report a case of a 65-year-old male who presented to his primary care physician with a 1-year history of reticular erythema and hyperpigmentation with focal ulceration on his right lateral leg. Histopathology on biopsy revealed mild hyperkeratosis and focal epidermal atrophy; however, the most striking finding was a proliferation of dermal vascular spaces lined by pleomorphic endothelial cells and numerous mitotic figures, which was morphologically compatible with angiosarcoma. However, clinicopathologic correlation and immunostaining revealed an actual diagnosis of erythema ab igne with reactive angiomatosis. Reactive angiomatosis-morphologically mimicking angiosarcoma-is a rarely reported feature of severe erythema ab igne, and dermatopathologists should be aware of this possibility to avoid misdiagnosis of erythema ab igne as angiosarcoma.

Pleomorphic Leiomyosarcoma Presenting as a Upper Back Epidermal Inclusion Cyst.

ABSTRACT: Leiomyosarcoma is a common sarcoma of both organs and soft tissues; however, large intradermal tumors are extremely rare. Presented is a pleomorphic leiomyosarcoma in a 64-year-old man, initially considered to be a ruptured epidermal inclusion cyst. The patient had a mildly tender, enlarging soft-tissue mass with a central pore on his right upper back. Incomplete extirpation showed a 5 × 5 cm heterogeneous, predominantly pleomorphic sarcoma with areas of fascicular and storiform spindled cells infiltrating the subcutaneous soft tissue to the underlying fascia and extending upward into the middle and upper dermis with prominent extension into pilosebaceous units. There were small foci with myxoid stroma and large areas of necrosis. CD31 demonstrated thin-walled curvilinear vessels throughout the tumor. The first desmin immunohistochemical stain near areas with myxoid stroma was negative but smooth muscle actin positive. However, desmin positivity was strong and diffuse in the spindled and more pleomorphic areas on 2 additional tissue sections. No rhabdomyoblasts or striated muscle fibers were seen. A diagnosis of pleomorphic leiomyosarcoma was rendered. This case highlights a unique clinical and histological presentation of a leiomyosarcoma initially mistaken to be a ruptured epidermal inclusion cyst, and the need to sometimes apply ancillary immunohistochemical studies to sections from more than one tissue block to accurately differentiate heterogeneous sarcomas with similar histologic features.

Fortuitous Eradication of an Aggressive Basal Cell Carcinoma Via Foreign Body Reaction to a Polyurethane Vacuum-Assisted Closure Sponge.

ABSTRACT: The foreign body reaction (FBR) is a well-documented immune reaction. Much of the literature on FBRs has focused on minimizing this immune response to mitigate the impact on medical implants. Here, we present a case that illustrates a serendipitous oncologic outcome from an FBR. A 54-year-old man presented with an aggressive basal cell carcinoma (BCC). At the first resection, he had broadly positive surgical margins. The surgical wound was temporized with a polyurethane wound vacuum assisted closure (VAC) device. He was lost to follow-up having retained a VAC sponge for a total of 12 weeks. A wide re-resection was performed 7 months after the initial resection. Exhaustive examination of the resected specimen was performed. There was an absence of any BCC, replaced by a widespread chronic FBR to polyurethane VAC sponge particles. This suggests that the foreign body immune response was sufficiently intense to eradicate any remaining BCC. This case illustrates the concept of an FBR as a novel method of local immunotherapy.

Unusual Case of a Caruncular Oncocytoma.

ABSTRACT: Oncocytomas are benign neoplasms that are most often found in the salivary glands and kidneys. Ocular oncocytoma typically present as an asymptomatic dark blue papule on the lacrimal caruncle. Histologically, the tumor is composed of oncocytes, cells notable for eosinophilic cytoplasmic granules representing large quantities of dysfunctional mitochondria. The neoplastic proliferation may be partially or totally encapsulated and may be surrounded by myoepithelial cells. Discussed is the pathophysiology and histopathology of an ocular oncocytoma from the right lacrimal caruncle of a 68-year-old man. The patient complained of a foreign body sensation and tearing associated with a purpuric 1 × 1-mm papule of the right caruncle that had been present for 6 months. An excisional biopsy showed an oxyntic neoplasm with small cystic glandular spaces associated with goblet cells and mucin, confirmed by mucicarmine stain. Given the rarity of ocular oncocytomas and presence of mucin, exclusion of an endocrine mucin-producing sweat gland carcinoma was necessary. Peripheral myoepithelial cells noted on p63 immunostaining are seen in both endocrine mucin-producing sweat gland carcinoma and oncocytomas. However, endocrine mucin-producing sweat gland carcinoma is excluded by the presence of goblet cells, the uniform oxyphilic cytoplasm of the epithelial cells, and the negative immunohistochemical staining for neuron-specific enolase, chromogranin, synaptophysin, estrogen receptor, and progesterone receptor. Complete surgical excision is the treatment of choice for oncocytomas. This case highlights the clinical and histopathological presentation of ocular oncocytomas and raises awareness of this rare entity for both the practicing dermatologist and dermatopathologist.

Caruncular Dacryops After Cataract Surgery With Histopathological Characterization.

ABSTRACT: Caruncular dacryops is a rare cyst of lacrimal tissue most commonly found in the palpebral lobe of the lacrimal gland. The exact cause of dacryops is unclear, although it may be congenital or associated with trauma, infection, or inflammation. The pathophysiology and histology of a caruncular dacryops of the left lacrimal gland in a 68-year-old woman is reported. The patient presented 3 months after a cataract surgery with symptoms of irritation and pruritus of the left eye. A 6- × 6-mm clear cyst of the lacrimal gland prolapsing into the lateral fornix was noted on physical exam. Histological examination of the cyst showed a double layer of flat cuboidal epithelium surrounded by fibrous tissue with minor lacrimal glands present. Periodic acid Schiff-diastase and mucicarmine staining showed the presence of goblet cells dispersed in the epithelial cells. Complete excision of the cyst is the treatment of choice for most caruncular dacryops, and our case remains without recurrence after excision. This case highlights the clinical and histological presentation of caruncular dacryops and raises awareness of their incidence following presumed trauma during cataract surgery.

Hidradenitis suppurativa at the knees.

Hidradenitis suppurativa is a poorly understood, destructive disease centered on pilosebaceous units and characterized by inflammatory nodules that progress to abscesses, sinus tracts, and scars. The typical patient is a young woman with involvement of the axillae, breasts, and groin. Presented is a 60-year-old man with poorly controlled diabetes, who initially developed pink-to-yellowish plaques with punched out ulcers on his knees that evolved to scars and draining sinus tracts. Draining sinus tracts were also noted under the left axilla. Histopathology revealed suppurative granulomatous inflammation centered on hair follicles as well as sinus tracts. Special stains for fungus and mycobacterial bacilli were negative. Cultures and PCR for mycobacterial tuberculosis were negative. The patient was diagnosed with hidradenitis suppurativa. A treatment trial of topical corticosteroids and antibiotics was given, but this regimen failed to improve his lesions. The patient was then started on adalimumab, which yielded marked improvement within three months. This case is reported because of the unusual clinical presentation and to highlight the spectrum of atypical hidradenitis suppurativa.