Symptomatic perineural and intraneural invasion of the trigeminal nerve and subsequent abducens Nerve palsy by cutaneous squamous cell carcinoma.

A 74-year-old woman who presented initially with trigeminal neuralgia of the left forehead and scalp was later found to have a poorly differentiated squamous cell carcinoma (SCC) with large-nerve perineural and intraneural invasion of the left supraorbital nerve. Negative histopathologic margins were achieved in three stages of permanent fixed tissue en face processing and the final defect was repaired with a large rotation flap. Approximately one month after repair, the patient presented with new-onset diplopia and was found to have a complete left cranial nerve VI palsy suspicious for continued disease spread. MRI confirmed perineural spread along the ophthalmic branch of the trigeminal nerve through the superior orbital fissure into the cavernous sinus. She was subsequently treated with radiation therapy (66Gy in 33 fractions). The involvement of two distinct cranial nerves by perineural invasion is uncommon and has mostly been described involving branches of the trigeminal and facial nerves. This case highlights the rare presentation of perineural invasion involving both the trigeminal nerve and the abducens nerve. Anatomically, this clinical presentation can be explained by the retrograde perineural spread along the ophthalmic branch of the trigeminal nerve through the supraorbital fossa into the cavernous sinus where these two nerves are in close proximity.

Epidermotropic Cutaneous Metastasis of Colonic Adenocarcinoma Presenting as a Sister Mary Joseph Nodule.

ABSTRACT: The Sister Mary Joseph nodule is a metastatic umbilical lesion that is seen in 1%-3% of intra-abdominal and pelvic malignancies. Cutaneous metastasis of visceral malignancies is rare and has characteristic dermal or subcutaneous involvement on histopathologic examination. Epidermotropism is described as the migration of malignant cells into the epidermis and is an unusual finding in intra-abdominal malignancies and cutaneous metastases. An 81-year-old woman with a past medical history of colorectal adenocarcinoma presented to the dermatology clinic for evaluation of an enlarging, denuded umbilical mass. A tangential biopsy was obtained and sent for histopathologic examination. Histopathologic analysis demonstrated infiltration of atypical, pleomorphic cells in the dermis with spread into the epidermis, consistent with epidermotropism. An immunohistochemical panel was performed and was consistent with cutaneous metastasis of the patient's underlying adenocarcinoma. We present a case of epidermotropic cutaneous metastasis of colorectal adenocarcinoma presenting as a Sister Mary Joseph nodule, an extremely rare occurrence that has not been well-documented in the literature.

Toxic epidermal necrolysis and Stevens-Johnson syndrome/toxic epidermal necrolysis overlap in pediatric patients with a focus on newer antiepileptic drugs: A 25-year retrospective study at a single tertiary care center.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis Syndrome (TEN) are rare immune-mediated diseases. Extensive research on adult triggers of SJS and TEN is available; however, research in children is more limited. OBJECTIVE: We sought to investigate and report the experience with pediatric SJS and TEN in our center, identifying associated medications. METHODS: A retrospective review from 1990 to 2015 at the Shriner's Burn Hospital in Galveston, Texas was performed to identify patients diagnosed with SJS, SJS/TEN overlap, and TEN. Data pertaining to demographic characteristics, medical history, physical exam, treatment, and outcomes were collected. RESULTS: We identified SJS/TEN overlap or TEN in 51 patients. Antiepileptic drugs were the most common group of causative agents, closely followed by antibiotics. The most common causative agents were trimethoprim-sulfamethoxazole, phenytoin, and lamotrigine used concomitantly with valproic acid. Newer generation agents, with the definition of agents approved after 1990, were the cause in 13/51 (25.5%) cases. Newer generation agents included lamotrigine, clobazam, and zonisamide. Seven patients died, resulting in a 13.7% mortality rate. Renal failure, liver failure, sepsis, and gastrointestinal involvement each had a statistically significant association with mortality. SCORTEN was statistically significantly greater in patients who died compared to children who lived (3 vs 2). LIMITATIONS: This is a retrospective study. CONCLUSION: Three drugs introduced into the market since 1990 have emerged as causes of SJS/TEN overlap and TEN: lamotrigine, clobazam, and zonisamide. These medications are being used more widely to treat seizures, as well as mood disorders. It is also important for clinicians to be aware of the extremely commonly used medications such as amoxicillin, tetracyclines, NSAIDs, and acetaminophen that can rarely cause SJS and TEN.

Basomelanocytic Neoplasms: A Report of Two Similar Tumors With Divergent Treatments.

Basomelanocytic neoplasms are tumors consisting of elements of both basal cell carcinoma and melanoma. These tumors are exceedingly rare and present a unique challenge as to how the melanoma component should be classified. Due to the paucity of cases, there are no clear-cut evidence-based guidelines as to how these tumors should be staged and which treatment options provide the optimal outcome. We present 2 separate patients with similar cases of colonizing basomelanocytic tumors that were treated in drastically different ways, highlighting the differing approaches to treatment. We discuss theses treatment modalities and the challenges inherent to diagnosing and treating basomelanocytic neoplasms.

Cutaneous nontuberculous mycobacteria infections: A retrospective case series of 78 patients from the Texas Gulf Coast region.

BACKGROUND: The incidence of cutaneous nontuberculous mycobacteria (NTM) infections is increasing. These infections are a diagnostic and therapeutic challenge. OBJECTIVE: We investigated the clinical features, diagnosis, and management of cutaneous NTM infections. METHODS: A retrospective case series studied 78 patients from a Gulf Coast tertiary referral center diagnosed with cutaneous NTM infection by culture or stain of a skin biopsy specimen. RESULTS: A history of trauma, procedure, or environmental exposure was common. The mean time between the initial evaluation and diagnosis was 12 weeks. Only 15% of acid-fast bacillus-positive cultures had a positive acid-fast bacillus smear, and only 43% of those accompanied by skin biopsy specimen had a positive Fite stain. Immunosuppressed patients were more likely to have a positive Fite stain. Treatment included surgery and multiple antibiotics. Immunosuppressed patients and Mycobacterium abscessus group infections were more likely to have persistent disease. LIMITATIONS: M chelonae and M abscessus isolates were indistinguishable and therefore were reported together. Five cases were not confirmed by culture. CONCLUSIONS: Even with clinical suspicion, the diagnosis of NTM infection can be difficult. Results of acid-fast bacillus smears and special stains are frequently negative. Antibiotic resistance is common. Multidrug treatment is often required, and surgical therapy may be needed.

Nephrogenic systemic fibrosis: A 15-year retrospective study at a single tertiary care center.

BACKGROUND: Despite multiple therapeutic approaches for nephrogenic systemic fibrosis (NSF), no single treatment has convincingly shown consistent benefit. The most successful outcomes have been associated with recovery of renal function, although evidence remains limited and past studies have been inconclusive. OBJECTIVE: We sought to investigate whether improvement of renal function via successful transplantation or via return of renal function after acute kidney injury correlates with improvement of NSF, and to further characterize the clinical features and progression of NSF. METHODS: A retrospective medical chart review led to the identification of patients (n = 8) diagnosed with NSF who presented to a single academic tertiary referral center over a 15-year period. These 8 patients were contacted by phone to obtain information related to treatment and clinical course of their NSF and renal function. Statistical analysis was performed using Fisher's exact test. RESULTS: There is a significant correlation (P = .0286) of improved renal function with improvement of NSF. All 4 patients who had improvement of renal function also had improvement of NSF. Two of these patients had end-stage renal disease and a successful kidney transplant, and two had acute kidney injury that resolved. No improvement in NSF was observed without kidney function resolution. LIMITATIONS: Our study is limited by a small sample size (n = 8) and a retrospective study design, which increased its potential for selection and recall bias. CONCLUSION: Improvement of renal function through either transplantation or resolution of acute kidney injury with medical management is significantly associated with improvement of NSF.

Chronic myelomonocytic leukemia masquerading as cutaneous indeterminate dendritic cell tumor: Expanding the spectrum of skin lesions in chronic myelomonocytic leukemia.

Chronic myelomonocytic leukemia (CMML) is a hematopoietic stem cell neoplasm exhibiting both myelodysplastic and myeloproliferative features. Cutaneous involvement by CMML is critical to recognize as it typically is a harbinger of disease progression and an increased incidence of transformation to acute myeloid leukemia. Cutaneous lesions of CMML exhibit heterogeneous histopathologic features that can be challenging to recognize as CMML. We describe a 67-year-old man with a 3-year history of CMML who had been managed on single-agent azacitidine with stable disease before developing splenomegaly and acute onset skin lesions. Examination of these skin lesions revealed a dense infiltrate of histiocytic cells morphologically resembling Langerhans type cells (lacking frank histopathologic atypia), and with the immunophenotype of an indeterminate cell histiocytosis (S100+ CD1a+ and langerin-). Given the history of CMML, next-generation sequencing studies were performed on the skin biopsy. These revealed a KRAS (p.G12R) mutation identical to that seen in the CMML 3 years prior, establishing a clonal relationship between the 2 processes. This case expands the spectrum for and underscores the protean nature of cutaneous involvement by CMML and underscores the importance of heightened vigilance when evaluating skin lesions of CMML patients.

Primary amyloidosis-induced nail dystrophy.

Primary amyloidosis is caused by a monoclonal proliferation of plasma cells and is capable of producing cutaneous lesions. A 56-year-old male was admitted to the hospital for evaluation of chronic back pain and acute lower extremity weakness. On examination, he was noted to have subungual verrucous plaques with overlying nail dystrophy on his bilateral thumbs. A biopsy of one subungual lesion showed a deposition of amorphous material in the dermis that stained with Congo red and crystal violet. These cutaneous lesions ultimately led to the diagnosis of plasma cell dyscrasia and primary amyloidosis. Based on the literature search, primary amyloidosis presenting with this degree of subungual thickening and overlying nail dystrophy has not been previously reported.

Firm papules on the penis and scrotum.

An 18-year-old man presented with a 6-year history of penile and scrotal papules. Biopsy of one of the 1-3mm papules revealed calcinosis cutis.

Condyloma lata of the umbilicus: A case report highlighting the present syphilis emergency.

Syphilis is an ancient sexually transmitted infection that plagues communities across the United States and the world. Cutaneous syphilis has a wide variety of manifestations and presentations, and is notoriously difficult to identify clinically as a result. In this report, we describe the case of a 30-year-old patient with condyloma lata on the umbilicus, an extremely rare site for the presentation of these lesions. With the recent surge in syphilis infections nationwide, including congenital infections, this case underscores the urgent necessity for heightened syphilis awareness and suspicion among clinicians.

Dual role of p53 amyloid formation in cancer; loss of function and gain of toxicity.

The tumor suppressor p53 plays an important role in genome integrity. It is frequently mutated in all types of human cancers, making p53 a key factor in cancer progression. Two phenotypic consequences of these alterations are dominant; a loss of function and a gain of function of p53, which, in several cases, accumulates in intracellular aggregates. Although the nature of such aggregates is still unclear, recent evidence indicates that p53 can undergo conformational transitions leading to amyloid formation. Amyloid diseases, such as, Alzheimer's disease, are characterized by the accumulation of insoluble aggregates displaying the fibrillar conformation. We decided to investigate the propensity of wild type p53 to aggregate and its consequent assembly into different amyloid species, such as oligomers and fibrils; and to determine if these changes in conformation lead to a loss of function of p53. Furthermore, we analyzed cases of Basal Cell Carcinoma (BCC), for the presence of p53 amyloids. Here, we show that p53 forms amyloid oligomers and fibrils, which coincide with p53 inability of binding to DNA consensus sequences. Both p53 amyloid oligomers and fibrils were detected in BCC cancer samples. Additionally, we demonstrate that p53 oligomers are the most cytotoxic to human cell cultures. Our study reveals p53 amyloid formation and demonstrates its dual role in the pathogenesis of cancer by producing a loss of protein function and a gain of toxic function, extensively described in several amyloidogenic diseases. Our results suggest that under certain circumstances, cancer could be considered a protein-conformation disease.

CT imaging of condyloma acuminata.

This case report shows the use of computed tomography (CT) imaging in evaluating a 53-year-old male patient presenting with anogenital wart like lesions. The patient was suspected of having condyloma acuminata. The significant extent of condyloma acuminata, as seen in this case, is a relatively uncommon finding. CT was ordered to help assess for local invasion and malignancy. This report also discusses Buschke-Lowenstein tumors, the rare malignant transformation of giant condyloma acuminata in the anogenital region. Invasion and malignancy in condyloma acuminata must be evaluated as they can have a poor and even fatal prognosis. Histological examination confirmed the diagnosis of condyloma acuminata and CT ruled out regional invasion, and metastatic disease. Additionally, the role of imaging in planning surgical excision is discussed. This case highlights the value of CT in the clinical diagnosis and management of condyloma acuminata.

Predictive value of margins in diagnostic biopsies of nonmelanoma skin cancers.

BACKGROUND: With geographic regional variation, nonmelanoma skin cancer biopsy reports include assessment of margins. When margins are reported as negative, clinical dilemmas may emerge concerning the necessity of additional treatment. OBJECTIVE: To evaluate the predictive value of biopsy margins with regard to residual tumor present in subsequent excisions of nonmelanoma skin cancers. METHODS: This is a retrospective review of 235 diagnostic nonmelanoma skin cancer biopsies and their corresponding excisions for margin status at biopsy, and the presence of residual tumor in subsequent excisions. RESULTS: Twelve of 148 squamous cell carcinomas (8.1%) had negative biopsy margins and all of the subsequent excisions were free of residual tumor. The squamous cell carcinomas with negative biopsy margins consisted predominantly of nonfacial, superficial tumors of the well-differentiated and keratoacanthoma subtype. Nine of 87 basal cell carcinomas (10.3%) had negative biopsy margins. Seven of those 9 (77.8%) had residual tumor present in subsequent excisions. LIMITATIONS: Statistical analysis performed reached significance, but with small sample size as only 21 of the biopsy specimens had negative margins. Also, residual tumor was determined via standard bread-loafing technique on excisions, which is known to examine only a proportion of the tissue and can lead to false-negative results. CONCLUSIONS: The results of this small pilot study suggest that negative-margin diagnostic biopsies may be therapeutic for well-differentiated or keratoacanthoma subtypes of squamous cell carcinoma because all subsequent excisions were devoid of tumor. Negative biopsy margins from basal cell carcinomas were not predictive of tumor removal.

Type I IFN receptor regulates neutrophil functions and innate immunity to Leishmania parasites.

Type I IFNs exert diverse effector and regulatory functions in host immunity to viral and nonviral infections; however, the role of endogenous type I IFNs in leishmaniasis is unclear. We found that type I IFNR-deficient (IFNAR-/-) mice developed attenuated lesions and reduced Ag-specific immune responses following infection with Leishmania amazonensis parasites. The marked reduction in tissue parasites, even at 3 d in IFNAR-/- mice, seemed to be indicative of an enhanced innate immunity. Further mechanistic analyses indicated distinct roles for neutrophils in parasite clearance; IFNAR-/- mice displayed a rapid and sustained infiltration of neutrophils, but a limited recruitment of CD11b+Ly-6C+ inflammatory monocytes, into inflamed tissues; interactions between IFNAR-/-, but not wild-type (WT) or STAT1-/-, neutrophils and macrophages greatly enhanced parasite killing in vitro; and infected IFNAR-/- neutrophils efficiently released granular enzymes and had elevated rates of cell apoptosis. Furthermore, although coinjection of parasites with WT neutrophils or adoptive transfer of WT neutrophils into IFNAR-/- recipients significantly enhanced infection, the coinjection of parasites with IFNAR-/- neutrophils greatly reduced parasite survival in WT recipients. Our findings reveal an important role for type I IFNs in regulating neutrophil/monocyte recruitment, neutrophil turnover, and Leishmania infection and provide new insight into innate immunity to protozoan parasites.

Syringitis: a clue to herpes infection.

Herpes simplex virus (HSV) is a member of the herpes virus family that commonly affects the skin. Typical histopathologic findings are usually limited to the epidermis and include intraepidermal vesicles or ulceration and epidermal necrosis. More specific findings in herpes virus infection include enlarged and pale keratinocytes, with steel-gray nuclei and margination of chromatin at the edge of the nucleus and ballooning degeneration. Although histopathologic changes may occasionally involve the hair follicles or sebaceous glands, it is very rare to find HSV involving the eccrine glands. We present a case of a 13-month-old child with a large body burn diagnosed with HSV (in the absence of the epidermis) by the presence of syringitis with herpetic features in the absence of the epidermis to aid in diagnosis.

Role of oligomers in the amyloidogenesis of primary cutaneous amyloidosis.

BACKGROUND: Primary cutaneous amyloidosis (PCA) describes a heterogeneous group of cutaneous diseases characterized by amyloid deposition; this may manifest as macules, papules, or nodules, depending on the subtype involved. To date, relatively little is known about the process of amyloidogenesis in the skin; however, investigators recently have identified small amyloid species, known as oligomers, which give rise to large amyloid fibrillar aggregates. OBJECTIVE: The purpose of the current study was to identify small oligomers in patients with PCA using novel immunohistochemical techniques and to examine our findings in light of previous hypotheses of amyloid formation in these diseases. METHODS: Six cases of PCA were analyzed using Congo red, thioflavin S, and hematoxylin-eosin. We also analyzed these samples with the novel oligomer-specific conformational antibody I-11 to detect the small, misfolded protein oligomers. Semiquantitative analysis was performed on these samples to grade the amount of amyloid aggregates and oligomers detected in the skin samples with light and polarized microscopy. RESULTS: In the cases examined, we detected intracellular oligomers in the basal cell layer of the epidermis and the surrounding cells in the dermis. We also were able to detect large aggregates of amyloid in our samples and to correlate the relationship of oligomers to amyloid aggregates in accordance with previous studies on cutaneous amyloidosis and other amyloid-related diseases. LIMITATIONS: Small sample size is a limitation. CONCLUSIONS: PCA is an amyloid-related disease that likely follows a similar mechanism as other more intensively studied amyloid diseases.