Unusual teeth in unusual places: Criteria for identifying teratomatous dental elements in archeological contexts.

OBJECTIVE: This paper describes the dental elements (i.e., teeth and incomplete tooth-like structures) formed by mature cystic teratomas and provide some diagnostic criteria to aid in their paleopathological identification and analysis. MATERIALS: Hard tissue structures from 13 clinically-derived mature cystic teratomas excised between 2003 and 2007. All are from female patients (N = 13) between the ages of 17 and 56. METHODS: A dental and osteological inventory identified number of teeth and tooth types present in each specimen. RESULTS: Of the 13 specimens, nine contained dental elements. The number per teratoma ranged from one to seven. A wide variety of tooth types were present in the teratomas with some teeth independent of, and others embedded within, bony matrices. CONCLUSIONS: While some teratoma teeth exhibit distinguishable types and laterality, the majority will exhibit some degree of abnormality in size, form, developmental completion, or association with other irregular bony elements. SIGNIFICANCE: Give the modern clinical prevalence and yet relatively few paleopathological cases reported, it is likely that mature teratomas are under-identified in the archeological record. The diagnostic criteria presented in this paper can aid paleopathologists in their identification and analysis of these neoplasms. LIMITATIONS: Precise paleopathological identification of teratoma elements can be difficult; particularly when they are no longer constrained or contextualized by unmineralized neoplastic borders. As such, there is a risk that such remnants may be mistaken for fetal parts or disassociated elements. SUGGESTIONS FOR FURTHER RESEARCH: Application of these criteria, paired with careful excavation techniques, is advised.

A case of oral foreign-body granuloma due to diatoms.

Diatoms are photosynthetic algae with a siliceous exoskeleton. Diatoms are utilized by a wide array of industries for applications such as filtration and pest control. Unsubstantiated claims have also propelled their societal reach to trendy oral and topical uses. This case highlights a rare case of an oral granuloma secondary to diatoms. An 80-year-old woman presented with a mobile, firm, asymptomatic submucosal mass on her lower left mandibular vestibular mucosa. Histopathology showed a non-caseating granulomatous reaction to diatoms. Her only verified contact with a diatomaceous earth product was a dental impression using alginate after upper front teeth trauma 5 months before. Although there have been several cases of allergic contact dermatitis attributed to diatoms, there are no reported cases of diatom-induced granuloma formation found in the literature. There are, however, ample data on granulomas initiated by silica. Given the silica-based composition of diatoms, and the broad use of diatoms in industry and alternative medicine, it is unclear why diatom-induced granulomas are not more widely described. This report may alert clinicians to the existence of diatom granulomas and incline them to tailor their history to cover questions about possible exposure when evaluating patients presenting with a localized oral lesion.

Neoplasm or not? General principles of morphologic analysis of dry bone specimens.

Unlike modern diagnosticians, a paleopathologist will likely have only skeletonized human remains without medical records, radiologic studies over time, microbiologic culture results, etc. Macroscopic and radiologic analyses are usually the most accessible diagnostic methods for the study of ancient skeletal remains. This paper recommends an organized approach to the study of dry bone specimens with reference to specimen radiographs. For circumscribed lesions, the distribution (solitary vs. multifocal), character of margins, details of periosteal reactions, and remnants of mineralized matrix should point to the mechanism(s) producing the bony changes. In turn, this allows selecting a likely category of disease (e.g. neoplastic) within which a differential diagnosis can be elaborated and from which a favored specific diagnosis can be chosen.

Amelanotic melanoma: a unique case study and review of the literature.

Amelanotic melanoma (AM) is a rare form of melanoma which lacks visible pigment. Due to the achromic manifestation of this atypical cutaneous malignancy, it has been difficult to establish clinical criteria for diagnosis. Thus, AM often progresses into an invasive disease due to delayed diagnosis. In this report, we describe the case of a 72-year-old Caucasian woman who had been diagnosed with AM after 3 years of failed treatments for what presented as a periorbital dermatitis. Her Clark's level 4, 1.30 mm thick melanoma required nine surgeries for successful resection and reconstruction. This case exemplifies the diagnostic pitfall of AM and the need for new criteria for early detection and management.

Drug rash with eosinophilia and systemic symptoms (DRESS) caused by phenytoin.

Drug rash with eosinophilia and systemic symptoms (DRESS) is a rare but potentially life-threatening condition with high mortality. Diagnosis is challenging due to variable clinical presentation and a protracted latency period following initiation of the offending drug. DRESS is a complex interplay that starts by introduction of the offending drug, reactivation of viruses and activation of the immune system. Herpes virus reactivation is considered a diagnostic marker and indicator of illness severity. Prompt recognition and the removal of offending agent remain the key to successful treatment. In cases of severe organ involvement, corticosteroids, immunoglobulins, antiviral and specialist consultation may be helpful. Here we present a case of a 36-year-old African-American male who presented with symptoms mimicking sepsis with an associated skin eruption that was diagnosed as DRESS.

High-Velocity Paint Gun Injuries.

Cutaneous injuries due to industrial high-pressure paint guns are well-documented in the literature; however, the histologic characteristics are uncommonly described, and facial involvement has not been previously reported. Histopathologic features of paint gun injuries vary depending on the time since injection and type of material. Early lesions display an acute neutrophilic infiltrate, edema, and thrombosis, with varying degrees of skin, fat, and muscle necrosis. More developed lesions (120-192 hours after injury) have prominent histiocytes and fibrosis around necrotic foci, possibly with the pitfall of muscle regenerative giant cells that could be mistaken for sarcoma. Continuing inflammation, swelling, and resultant vascular compression could explain ongoing necrosis months after the accident. The histopathologic differential diagnosis in the absence of clinical history includes paint in an abrasion, foreign body reaction to tattoo, giant cell tumor of tendon sheath, and various neoplasms. If available, radiologic studies can substitute for clinical photographs to indicate the extent of injury. The radiologic differential, uninformed by history, may include calcific periarthritis, gouty tophus, and tumoral calcinosis. Seven cases of injury due to high-velocity paint guns are presented with 4 additional cases mimicking paint gun injury and with review of the literature.

Cutaneous Balamuthia mandrillaris infection as a precursor to Balamuthia amoebic encephalitis (BAE) in a healthy 84-year-old Californian.

Soil and freshwater-dwelling amoebae may opportunistically infect the skin and evoke a granulomatous dermatitis that camouflages their underlying morphology. Amoebic infestations are incredibly rare in the U.S., predominantly occurring in the young, elderly, and immunocompromised. Sadly, because diagnosis is difficult and unsuspected, most cases are diagnosed at autopsy. The following case is of a healthy 84-year-old man with a non-healing nodulo-ulcerative cutaneous lesion on his left forearm that appeared following a gardening injury. Lesional punch biopsies repeatedly showed non-specific granulomatous inflammation with no pathogens evident histologically or by culture. Histopathologic diagnosis was made five months after initial presentation via identification of amoebic trophozoite forms in tissue from a large excisional specimen. Anti-amoebic therapy was initiated immediately. The patient experienced mental status changes three days following lesion excision, with evidence of a cystic mass in the left medial parieto-occipital lobe by CT. Both intraoperative brain biopsies and cutaneous tissue samples tested positive for Balamuthia mandrillaris by indirect immunofluorescent antibody assay performed at the Centers for Disease Control. The patient achieved a full recovery on a triple antibiotic regimen. Clinical suspicion and thorough histopathologic analysis may determine the difference between survival and death for a patient presenting with a treatment-refractory localized granulomatous lesion.

Giant Basal Cell Carcinomas Express Neuroactive Mediators and Show a High Growth Rate: A Case-Control Study and Meta-Analysis of Etiopathogenic and Prognostic Factors.

BACKGROUND: Giant basal cell carcinomas (GBCCs), (BCC ≥ 5 cm), are often painless, destructive tumors resulting from poorly understood patient neglect. OBJECTIVES: To elucidate etiopathogenic factors distinguishing GBCC from basal cell carcinoma (BCC) and identify predictors for disease-specific death (DSD). METHODS: Case-control study examining clinicopathologic and neuroactive factors (ß-endorphin, met-enkephalin, serotonin, adrenocorticotropic hormone, and neurofilament expression) in GBCC and BCC. Systematic literature review to determine DSD predictors. RESULTS: Thirteen GBCCs (11 patients) were compared with 26 BCCs (25 patients). GBCC significantly differed in size, disease duration, and outcomes; patients were significantly more likely to live alone, lack concern, and have alcoholism. GBCC significantly exhibited infiltrative/morpheic phenotypes, perineural invasion, ulceration, and faster growth. All neuromediators were similarly expressed. Adenoid phenotype was significantly more common in GBCC. Adenoid tumors expressed significantly more ß-endorphin (60% vs. 18%, P = 0.01) and serotonin (30% vs. 4%, P = 0.02). In meta-analysis (n ≤ 311: median age 68 years, disease duration 90 months, tumor diameter 8 cm, 18.4% disease-specific mortality), independent DSD predictors included tumor diameter (cm) (hazard ratio (HR): 1.12, P = 0.003), bone invasion (HR: 4.19, P = 0.015), brain invasion (HR: 8.23, P = 0.001), and distant metastases (HR: 14.48, P = 0.000). CONCLUSIONS: GBCC etiopathogenesis is multifactorial (ie, tumor biology, psychosocial factors). BCC production of paracrine neuromediators deserves further study.

Dermal Titanium Dioxide Deposition Associated With Intralesional Triamcinolone Injection.

Cutaneous discoloration secondary to dermal deposition of titanium dioxide (TiO2) particles is recognized but seldom reported in the literature. In this report, the authors describe the case of a 61-year-old gentleman, with a long history of alopecia areata, who presented with numerous, discrete dark blue macules on the scalp. Scanning electron microscopy with energy dispersive x-ray spectroscopy analysis ultimately identified the macules as deposits of TiO2. The patient had a history of intralesional triamcinolone injections for management of alopecia areata. A sample of generic 0.1% triamcinolone acetonide paste was analyzed and found to contain many TiO2 particles analogous to those seen in the patient's biopsy sample. To the authors' knowledge, this is the first reported case of TiO2 deposition in the dermis likely resulting from topical combined with intralesional triamcinolone injection.

Ischemic fasciitis: enhanced diagnostic resolution through clinical, histopathologic and radiologic correlation in 17 cases.

Ischemic fasciitis is a pseudosarcomatous nodule or mass resulting from sustained or repeated pressure and consequent ischemia of soft tissue. Fibrin and hemorrhage expand its hypocellular epicenter bordered by enlarged (atypical, ischemic) fibroblasts and reactive vascular prominence resulting in diagnostically important histologic zonation. Although classically in bedridden patients, ischemic fasciitis owing to posture-related intermittent pressure in ambulatory adults is not well characterized; there has not been a thorough review of its presentation in ambulatory patients in the dermatology/dermatopathology literature. This article reviews the clinical, pathologic and radiologic presentation of 17 cases of ischemic fasciitis diagnosed over a 14-year period. Eighty-six percent of the six cases submitted by non-dermatologists were limb girdle/trunk lesions averaging 6.7 cm in greatest diameter while 90% of the eleven lesions submitted by dermatologists were elbow and forearm lesions averaging 2.3 cm. In no case was the diagnosis anticipated pre-biopsy by clinician or radiologist. Dermatologists submitted the majority of cases. Because ischemic fasciitis may simulate soft tissue sarcoma clinically and histologically, diagnosis helps prevent overtreatment. Zonal histopathologic structure may be shown by any form of biopsy and should motivate correlation with available radiologic studies. Importantly, determining a history of postural pressure at the site confirms the histopathologic diagnosis and avoids unnecessary excision.

Mutations Affecting Keratin 10 Surface-Exposed Residues Highlight the Structural Basis of Phenotypic Variation in Epidermolytic Ichthyosis.

Epidermolytic ichthyosis (EI) due to KRT10 mutations is a rare, typically autosomal dominant, disorder characterized by generalized erythema and cutaneous blistering at birth followed by hyperkeratosis and less frequent blistering later in life. We identified two KRT10 mutations p.Q434del and p.R441P in subjects presenting with a mild EI phenotype. Both occur within the mutational "hot spot" of the keratin 10 (K10) 2B rod domain, adjacent to severe EI-associated mutations. p.Q434del and p.R441P formed collapsed K10 fibers rather than aggregates characteristic of severe EI KRT10 mutations such as p.R156C. Upon differentiation, keratinocytes from p.Q434del showed significantly lower apoptosis (P-value<0.01) compared with p.R156C as assessed by the TUNEL assay. Conversely, the mitotic index of the p.Q434del epidermis was significantly higher compared with that of p.R156C (P-value<0.01) as estimated by the Ki67 assay. Structural basis of EI phenotype variation was investigated by homology-based modeling of wild-type and mutant K1-K10 dimers. Both mild EI mutations were found to affect the surface-exposed residues of the K10 alpha helix coiled-coil and caused localized disorganization of the K1-K10 heterodimer. In contrast, adjacent severe EI mutations disrupt key intermolecular dimer interactions. Our findings provide structural insights into phenotypic variation in EI due to KRT10 mutations.

Pemphigus vulgaris in pregnancy.

We report the case of a 34-year-old woman who was diagnosed with pemphigus vulgaris (PV) during pregnancy. The patient presented with widespread blistering dermatitis and associated burning and pruritus. At 6 weeks' gestation the patient was admitted to the hospital to expedite her diagnosis and initiate treatment. A skin biopsy revealed suprabasal acantholysis, and direct immunofluorescence demonstrated diffuse intercellular IgG in the epidermis and basal intercellular C3, which confirmed the diagnosis of PV. Treatment with corticosteroids was instituted after discussions with the patient about possible adverse effects to the fetus. Pemphigus vulgaris is rare in pregnancy and active PV presents potential threats of fetal spread and transient lesion production, which is associated with increased mortality and morbidity in the fetus. Our patient had active PV and required treatment throughout her pregnancy. The pregnancy progressed to premature delivery of the neonate without skin lesions or apparent complications.

Mixed Pneumocystis and Cryptococcus cutaneous infection histologically mimicking xanthoma.

Cutaneous Pneumocystis jirovecii infection is rare. It is thought that the disease emerges from a latent infection delivered via hematogenous and/or lymphatic dissemination from a primary lung infection in immunocompromised individuals. A 32-year-old human immunodeficiency virus-positive male was admitted for headache and vomiting. He was diagnosed with meningitis due to Cryptococcus neoformans and sputum tested positive for Pneumocystis. Six months later, he presented with a slightly crusted yellowish brown plaque and 2 similar but smaller papules with telangiectasia near the right angle of the mouth. Biopsy of the area featured histiocytes expanded by foamy cytoplasm as in a xanthoma except that the vacuoles were coarser. Special stains ultimately demonstrated the characteristic disks of Pneumocystis accompanied by a minor component of budding yeasts (Cryptococcus) in the same fields. This case illustrates the utility of adequate special stains in recognizing a mixed cutaneous infection, particularly in human immunodeficiency virus-positive patients, when microscopy presents an odd xanthoma-like lesion.

Calcific periarthritis: more than a shoulder problem: a series of fifteen cases.

BACKGROUND: Calcific periarthritis, referring to a circumscribed juxta-articular deposit of minute non-birefringent mineral grains, is rarely the clinical diagnosis accompanying a pathologic specimen. Familiarity with the clinical, pathologic, and radiologic manifestations of calcific periarthritis, particularly when encountered adjacent to joints other than the shoulder, facilitates diagnosis and may obviate biopsy, avoid confusion with other entities, and speed appropriate treatment. METHODS: Pathologic specimens that fulfilled the criteria for a diagnosis of calcific periarthritis were prospectively collected. Clinical history and radiologic studies were acquired and analyzed. Well-controlled special stains were employed on two specimens with a neutrophilic infiltrate that excluded fungal and bacterial agents, as corroborated by microbiologic cultures showing no growth. RESULTS: Over a five-year period, fifteen patients between the ages of thirty-one and eighty-eight years (mean age, fifty-nine years) presented to various local healthcare providers for treatment of juxta-articular swelling that was subsequently determined to be calcific periarthritis. In seven patients, deposits were alongside a toe joint; in five, alongside a finger joint; and in three, involving the shoulder. The majority of the patients were female (73%). No patient had a documented recurrence of calcific periarthritis in follow-up periods ranging from eighteen to eighty-seven months (average forty-five months). CONCLUSIONS: Of twelve histologically verified cases of calcific periarthritis adjacent to joints other than the shoulder, in only one patient (toe) was the preoperative clinical diagnosis accurate, which signals the need for greater awareness of this entity as a differential diagnostic option.

Conidiobolomycosis in a young Malaysian woman showing chronic localized fibrosing leukocytoclastic vasculitis: a case report and meta-analysis focusing on clinicopathologic and therapeutic correlations with outcome.

BACKGROUND: Conidiobolomycosis (also known as rhinoentomophthoramycosis) is a rare cutaneous/mucosal fungal infection seen mainly in the tropical rain forest regions of the world that can be associated with disfiguring facial elephantiasis, and rarely, death. OBJECTIVE: To present an exemplary case report and perform a systematic review of the world's literature to more accurately describe the natural history and the effect of therapy on outcome in conidiobolomycosis. METHODS: Case report and meta-analysis of published case reports and series of conidiobolomycosis to determine which clinical, pathologic, mycologic, and treatment factors impact on prognosis. RESULTS: We document delay in diagnosis of conidiobolomycosis in a young Malaysian woman, whose biopsy showed pathognomonic features-massive tissue eosinophilia and Splendore-Hoeppli phenomenon surrounding broad hyphae. These findings coexisted with granuloma faciale-like changes (fibrosing leukocytoclastic vasculitis) and lymphedema. Treatment with multiple antifungals was followed by complete resolution. For the meta-analysis, pooled data from 199 cases (162 with full outcome data) from 120 reports revealed a similar course for most cases: a disease affecting healthy young adults who present with progressive nasal symptoms (eg, nasal obstruction) and central facial swelling and show improvement or cure after surgical excision and/or treatment with one or more antifungal agents in 83%. Persistent-progressive facial disease occurred in 11%, and 6% died rapidly of fungal infection. Presentation with facial elephantiasis correlated with persistent-progressive rhinoentomophthoramycosis and a longer duration of disease before diagnosis (P = 0.02). Lethal infections were significantly associated with nonstereotypical presentation (eg, orbital cellulitis), visceral infection, absence of the Splendore-Hoeppli phenomenon, presence of comorbidities (eg, immunosuppression, hematolymphoid malignancy), infection with Conidiobolus incongruus or Conidiobolus lamprauges (not Conidiobolus coronatus), lack of response to amphotericin B, and female sex (all P ≤ 0.002). The few sensitivity studies performed demonstrated in vitro multidrug resistance of Conidiobolus species to most available antifungal agents. LIMITATIONS: Publication bias, reporting heterogeneity, and data deficits may affect results. CONCLUSIONS: Conidiobolomycosis should be included in the differential diagnosis of patients who present with nasal symptoms and painless centrofacial swelling. Massive tissue eosinophilia and Splendore-Hoeppli material coating thin-walled hyphae confirms the clinical diagnosis. The granuloma faciale-like histology found in this case can explain the onset of facial lymphedema by fibroinflammatory destruction of lymphatic vessels; the duration of disease and severity of inflammation likely predicts whether the lymphedema is reversible or not. Although rhinoentomophthoramycosis ostensibly responds in vivo to most available antifungal agents, routine culture and susceptibility testing is recommended to better define the efficacy of these therapeutic agents.

Mucoepidermoid carcinoma of the parotid presenting as periauricular cystic nodules: a series of four cases.

Mucoepidermoid carcinoma is a relatively common neoplasm of the major and minor salivary glands that can secondarily involve skin. In the vicinity of the ear lobe, mimicry of a benign cyst, both clinically and histopathologically is a diagnostic pitfall to avoid. The clinical manifestations, diagnostic histopathology, and clinical course of mucoepidermoid carcinoma of the parotid gland presenting as a clinically benign periauricular cystic nodule in four patients ranging in age from 11 to 63 years, are analyzed in the present report. Illustrating the challenge of accurate diagnosis, three of the four cases were initially misinterpreted on biopsy as benign cystic lesions. Multiple biopsies displayed foamy histiocytes around mucinous extravasations into dermis that mimicked ruptured epithelial cysts in two cases before malignancy was ascertained. This series demonstrates the need to include parotid tumor in the differential diagnosis of odd periauricular cyst-like expansions and adenosquamous proliferations. Mucoepidermoid carcinoma in particular can explain indolent, infra-auricular 'mucinous cysts'. Familiarity with this syndrome should arouse suspicion of parotid carcinoma when a 'cyst' or nodule is located near the earlobe. Delay in diagnosis results in larger surgical procedures than are otherwise necessary.

Surfer's toe: trauma-induced idiopathic acro-osteolysis in the toes of a 46-year-old surfer: a case report.

Acquired acro-osteolysis (AOL) is defined as the resorption of bone from the tufts or shafts of the terminal phalanges. Acquired acro-osteolysis can manifest as a primary osteolysis syndrome and also appears in a number of disease states including rheumatologic disorders, neuropathic diseases, the result of prolonged exposure to polyvinyl chloride, and in rare cases, as a response to repeated mechanical stress. In this report, a 46-year-old surfer was evaluated for AOL as a complication of sports-related repetitive trauma to the right second and third toes. Radiography showed the bony tips of his right second and third toes had been eroded away. Acquired acro-osteolysis in the surfer's toes resulted from increased blood flow initiated to repair microdamage caused by repeated trauma to the distal ends of his second and third right toes due to the habitual dragging of the affected toes across a surfboard. The always initial lytic phase of bone repair was magnified by the increased arterial input to warm the extremities after prolonged exposure to cold. At 6-years' follow-up, the use of a protective bandage while surfing has permitted full regeneration of the affected toes.

Frontal sinus osteoma with osteoblastoma-like histology and associated intracranial pneumatocele.

Osteomas of the cranial sinuses are rare, benign bony tumors that can be complicated by the formation of an intracranial pneumatocele. If not treated promptly, a pneumatocele can lead to abscess formation, meningitis, or ventriculitis. In the present case, an intracerebral pneumatocele was formed when an 18 cm(3) osteoma breached the posterior wall of the frontal sinus creating a one-way valve through which air could enter the intracranial cavity. The patient presented after forceful sneezing with nonspecific symptoms of headache, nausea, and vomiting. CT demonstrated a frontal collection of loculated air with mass effect within the left cerebral hemisphere. A partly mineralized mass occupied the left superior nasal ethmoid sinus and left frontal sinus. Of interest pathologically in this case, the tumor had a substantial osteoblastoma-like component. Surgical repair involved frontal craniotomy to remove the osteoma and debride frontal sinus mucosa, plugging the frontal nasal ducts and sinus with fat and bone wax, and dural restoration using an underwater closed drainage system to vent intracranial air and stabilize the patient.