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Biomedical subjects

Ronald J Barr

Publications and source records attributed to Ronald J Barr.

At least 19 recordsLinked to original sources

Changes of epidermodysplasia verruciformis in benign skin lesions: the EV acanthoma.

Foci of histological changes of epidermodysplasia verruciformis (EV) were noted in five benign skin lesions. These skin lesions included an intradermal nevus, a pigmented seborrheic keratosis, an isolated papule on the forearm, a perianal lesion, and an acantholytic acanthoma. Because the changes resembled true EV so strongly despite the absence of clinical EV in these patients, we searched for EV-human papilloma virus (HPV) types in these skin lesions. Polymerase chain reaction (PCR) analysis on the formalin-fixed, paraffin-embedded blocks was performed. As a positive control, we included tissue from two HIV-positive patients with clinical EV proven by biopsy. Studies were also performed on five other archived biopsies that did not show changes of EV on multiple tissue sections. A nested PCR method detected EV-HPV types in three of the five benign skin lesions showing EV changes as well as in the positive controls. EV changes and EV-HPV can be found incidentally on biopsy in the absence of clinical EV; when such changes are the major histopathological finding in an isolated skin lesion, the lesion should be termed an EV acanthoma.

Acanthoma↗

Papillated Bowen disease, a distinct variant.

Bowen disease usually presents as an irregular, asymptomatic, scaly or crusted erythematous plaque that can occur anywhere on the skin. An unusual clinicopathologic variant is described which presents as a well-circumscribed, papillated, exophytic and endophytic, sometimes keratotic lesion. This papillated variant of Bowen disease exhibits keratinocytes with prominent perinuclear halos suggestive of koilocytic change associated with human papillomavirus (HPV) infections. Classic Bowen disease has been associated in previous studies with a variety of HPV types, especially types 16, 18, and 31. Twenty-six patients with papillated Bowen disease were evaluated. The patients included 15 males and 11 females, ranging in age from 33 to 87 years old. Fifty-four percent (14) of the lesions involved the head and neck, 8% (2) involved the trunk, and the remaining 38% (10) involved extremities (including 3 lesions from the hands). Lesions were examined using in situ hybridization with widely screening genomic probes for HPV types 6, 11, 16, 18, 30, 31, 33, 35, 45, 51, and 52. None of the specimens contained HPV DNA from the more common oncogenic HPV types. Given the striking histologic appearance of these lesions, however, this does not exclude HPV infection detectable by more sensitive screening methods such as polymerase chain reaction. Papillated Bowen disease is distinct from other variants, including the verrucous-hyperkeratotic type.

Adult↗

Cutaneous squamous cell carcinoma: a comprehensive clinicopathologic classification--part two.

Cutaneous squamous cell carcinoma (SCC) includes many subtypes with widely varying clinical behaviors, ranging from indolent to aggressive tumors with significant metastatic potential. However, the tendency for pathologists and clinicians alike is to refer to all squamoid neoplasms as generic SCC. No definitive, comprehensive clinicopathological system dividing cutaneous SCCs into categories based upon their aggressiveness has yet been promulgated. Therefore, we have proposed the following based upon the malignant potential of SCC variants, separating them into categories of low (< or = 2% metastatic rate), intermediate (3-10%), high (greater than 10%), and indeterminate behavior. Low-risk SCCs include SCC arising in actinic keratosis, HPV-associated SCC, tricholemmal carcinoma, and spindle cell SCC (unassociated with radiation). Intermediate-risk SCCs include adenoid (acantholytic) SCC, intraepidermal epithelioma with invasion, and lymphoepithelioma-like carcinoma of the skin. High-risk subtypes include de novo SCC, SCC arising in association with predisposing factors (radiation, burn scars, and immunosuppression), invasive Bowen's disease, adenosquamous carcinoma, and malignant proliferating pilar tumors. The indeterminate category includes signet ring cell SCC, follicular SCC, papillary SCC, SCC arising in adnexal cysts, squamoid eccrine ductal carcinoma, and clear-cell SCC. Subclassification of SCC into these risk-based categories, along with enumeration of other factors including tumor size, differentiation, depth of invasion, and perineural invasion will provide prognostically relevant information and facilitate the most optimal treatment for patients.

Carcinoma, Squamous Cell↗

Cutaneous squamous cell carcinoma: a comprehensive clinicopathologic classification. Part one.

Cutaneous squamous cell carcinoma (SCC) includes many subtypes with widely varying clinical behaviors, ranging from indolent to aggressive tumors with significant metastatic potential. However, the tendency for pathologists and clinicians alike is to refer to all squamoid neoplasms as generic SCC. No definitive, comprehensive clinicopathological system dividing cutaneous SCCs into categories based upon their aggressiveness has yet been promulgated. Therefore, we have proposed the following based upon the malignant potential of SCC variants, separating them into categories of low (< or = 2% metastatic rate), intermediate (3-10%), high (greater than 10%), and indeterminate behavior. Low-risk SCCs include SCC arising in actinic keratosis, HPV-associated SCC, tricholemmal carcinoma, and spindle cell SCC (unassociated with radiation). Intermediate-risk SCCs include adenoid (acantholytic) SCC, intraepidermal epithelioma with invasion, and lymphoepithelioma-like carcinoma of the skin. High-risk subtypes include de novo SCC, SCC arising in association with predisposing factors (radiation, burn scars, and immunosuppression), invasive Bowen's disease, adenosquamous carcinoma, and malignant proliferating pilar tumors. The indeterminate category includes signet ring cell SCC, follicular SCC, papillary SCC, SCC arising in adnexal cysts, squamoid eccrine ductal carcinoma, and clear-cell SCC. Subclassification of SCC into these risk-based categories, along with enumeration of other factors including tumor size, differentiation, depth of invasion, and perineural invasion will provide prognostically relevant information and facilitate the most optimal treatment for patients.

Carcinoma, Squamous Cell↗

Evaluation of single versus multiple cryogen spray cooling spurts on in vitro model human skin.

Many commercially available dermatologic lasers utilize cryogen spray cooling for epidermal protection. A previous tissue culture study demonstrated that single cryogen spurts (SCS) of 80 ms or less were unlikely to cause cryo-injury in light-skinned individuals. More recently, multiple cryogen spurts (MCS) have been incorporated into commercial devices, but the effects of MCS have not been evaluated. The aim was to study an in vitro tissue culture model and the epidermal and dermal effects of SCS vs patterns of shorter MCS with the same preset total cryogen delivery time (Deltat(c)) and provide an explanation for noted differences. Four different spurt patterns were evaluated: SCS: one 40-ms cryogen spurt; MCS2: two 20-ms cryogen spurts; MCS4: four 10-ms cryogen spurts; MCS8: eight 5-ms cryogen spurts. Actual Deltat(c) and total cooling time (Deltat(Total)) were measured for each spurt pattern. RAFT tissue culture specimens were exposed to cryogen spurt patterns and biopsies were taken immediately and at days 3 and 7. Actual Deltat(c) was increased while Deltat(Total) remained relatively constant as the preset Deltat(c) of 40 ms was delivered as shorter MCS. Progressively more epidermal damage was noted with exposure to the MCS patterns. No dermal injury was noted with either SCS or MCS. For a constant preset Deltat(c) of 40 ms, delivering cryogen in patterns of shorter MCS increased the actual Deltat(c) and consequently the observed epidermal cryo-injury as compared to an SCS.

Apoptosis↗

Metaplastic breast carcinoma histologically mimicking cutaneous spindle cell squamous cell carcinoma.

Squamous cell carcinoma is one of the most common primary cutaneous carcinomas but on rare occasion, metastatic squamous cell carcinoma from a distant site or solid organ can present as a cutaneous lesion. Most metastases occur as dermal nodules or involve the dermal lymphatics, but when they are intimately associated with the epidermis, distinguishing the lesion as primary or metastatic may be extremely difficult and usually requires a clinical history or high index of suspicion. A 71-year-old woman presented with multiple eruptive nodules over her chest, flank, and back. Histologically the lesions appeared to be arising from the surface epithelium and consisted of atypical, predominantly spindle cells, some of which streamed off of the epidermis. Following the initial evaluation, a history of breast carcinoma with subsequent radiation therapy and ultimate mastectomy was obtained, and the original breast biopsy and mastectomy material was reviewed. After performing additional studies, it became clear that the origin of the carcinomas was metastatic from an underlying metaplastic breast carcinoma.

Aged↗

Exogenous and endogenous cutaneous anomalies and curiosities.

Exogenous and endogenous substances can produce some interesting cutaneous abnormalities. Exogenous lesions are externally introduced materials or foreign bodies. Endogenous lesions are substances that result from tissue host response to an injury or physical insult. There may be an overlap of these endogenous and exogenous lesions such that externally introduced materials can lead to peculiar tissue reactions. Pathologists should be aware of these anomalies as many of them can simulate neoplasms (ie, Monsel's reaction, polyvinylpyrrolidone disease, silica reaction) and inflammatory (ie, paraffinoma) and infectious processes (ie, Drysol(R) reaction and Lycopodium granuloma). The most interesting and important entities within each of these categories are presented with essential clinical and pathologic descriptions.

Artifacts↗

Primary cutaneous myxofibrosarcoma mimicking pleomorphic hyalinizing angiectatic tumor (PHAT): a potential diagnostic pitfall.

Myxofibrosarcoma (MFS) is one of the most common sarcomas of adults, and includes lesions ranging from low to high grade based on increasing cellularity, nuclear pleomorphism, and mitotic activity. We present an unusual case of MFS, which initially showed features of a pleomorphic hyalinizing angiectatic tumor (PHAT), a rare soft-tissue tumor considered benign in the WHO classification. The initial lesion showed a subcutaneous proliferation of spindled to polygonal eosinophilic cells with striking cellular pleomorphism, set in a myxoid to sclerotic stroma with prominent hyalinized and angiectatic vasculature, classic characteristics of PHAT. Rare mitotic figures were identified. The preliminary diagnosis of PHAT was confirmed by a consultant expert soft-tissue pathologist. Four months after the initial surgery, local recurrence was noted. The recurrent tumor demonstrated findings of a high-grade MFS, with a diffuse and cellular proliferation of atypical spindle cells set in a prominent myxoid stroma. Multiple mitoses, including atypical ones, were present. In light of these findings, the original specimen was reexamined and the initial diagnosis was amended to MFS. MFS may mimic or be confused with several benign soft-tissue lesions. Cases mimicking PHAT have not been previously reported. We describe a unique case of a high-grade MFS that initially showed characteristic features of a PHAT, to illuminate the fact that MFS may rarely arise in, or have areas that masquerade as, PHAT. It is also conceivable, although speculative, that at least some cases of PHAT, currently considered a benign tumor by the WHO, may actually represent or evolve into a unique form of MFS of low malignant potential.

Aged↗

Evaluation of cryogen spray cooling exposure on in vitro model human skin.

BACKGROUND AND OBJECTIVES: Cryogen spray cooling (CSC) is commonly used during dermatologic laser surgery. The epidermal and dermal effects of CSC have not been adequately evaluated. To study the potential for epidermal and dermal injury after CSC using an in vitro model of human skin (RAFT). STUDY DESIGN/MATERIALS AND METHODS: RAFT specimens were exposed to continuous CSC spurt durations of 10, 20, 40, 80, 100, 200, or 500 milliseconds. Biopsies were taken acutely, 3 and 7 days post-CSC exposure. Sections were stained with hematoxylin and eosin for evaluation of possible injury, Ki-67 to determine keratinocyte viability, and Melan-A, to identify and evaluate melanocytes. RESULTS: Minimal, transient epidermal changes were noted in specimens exposed to continuous CSC spurts of 80 milliseconds or less. Keratinocytes and melanocytes remained viable. Continuous CSC spurts of 100, 200, or 500 milliseconds (much longer than recommended for clinical use) resulted in significant epidermal injury acutely, with partial or full thickness epidermal necrosis at 7 days. Only the 500 milllisecond specimen demonstrated dermal change, decreased fibroblast proliferation at 3 days. CONCLUSIONS: Continuous CSC spurts of 80 milliseconds or less induce minimal, if any, epidermal or dermal damage and are unlikely to produce cryo-injury when used during dermatologic laser surgery.

Administration, Topical↗

Unguioblastoma and unguioblastic fibroma--an expanded spectrum of onychomatricoma.

Onychomatricoma is a rare tumor that appears to originate from cells of the nail matrix. Three cases of onychomatricoma that met Perrin et al.'s1 histologic criteria of onychomatricoma are described. However, using a single term to classify all three tumors ignores the apparent microscopic differences that exist among them. To demonstrate better the spectrum of so-called onychomatricoma and properly acknowledge the noticeable disparity among our cases, a series of terms is proposed. This terminology is based on the histologic spectrum of epithelial-stromal ratio of stromal cellularity and of extent nuclear pleomorphism. Use of such criteria has a precedent in the classification of follicular and odontogenic fibroepithelial neoplasms. This new nomenclature includes "unguioblastoma" for tumors with a predominant epithelial component and "unguioblastic fibroma" for tumors where a cellular stroma is more prominent and characteristic. The term "atypical unguioblastic fibroma" is used to describe a third rare neoplasm, in which the cellular stroma shows nuclear pleomorphism and atypia with an increase of mitotic activity.

Adult↗

Nuclear morphometry and molecular biomarkers of actinic keratosis, sun-damaged, and nonexposed skin.

Computer-assisted image analysis is useful for quantifying the histologic and molecular changes of sun-induced squamous cell carcinoma progression. We used the CAS 200 image analysis system to measure nuclear morphometric parameters, p53 expression, and proliferation markers in actinic keratosis (AK), sun-exposed, and normal skin in 51 patients. Nuclear morphometry revealed significant increases in nuclear absorbance, irregularity of nuclear shape, and nuclear size in AK compared with normal and sun-damaged skin. These parameters showed significantly greater variability in AK nuclei. Argyrophyllic nucleolar organizer area and number were also significantly greater in AK compared with sun-damaged skin and normal skin. Ki67 and p53 expressions were both increased in sun-damaged skin relative to normal and greater still in AK. These data are evidence that sun damage induces proliferation and p53 abnormalities before the appearance of nuclear abnormalities and their associated DNA instability. Following these changes during a skin cancer chemopreventative trial can then help assess the efficacy of the agent and help determine where in the progression of neoplastic changes it exerts its biological effects.

Adult↗

CD1a expression in psoriatic skin following treatment with propylthiouracil, an antithyroid thioureylene.

BACKGROUND: The antithyroid thioureylenes, propylthiouracil (PTU) and methimazole (MMI), are effective in the treatment of patients with plaque psoriasis. The mechanism of action of the drugs in psoriasis is unknown. Since the drugs reduce circulating IL-12 levels in patients with Graves' hyperthyroidism, the effect of propylthiouracil on CD1a expression in psoriatic lesions was examined in biopsy samples of patients with plaque psoriasis. CD1a is a marker of differentiated skin antigen presenting cells (APC, Langerhans cells). Langerhans cells and skin monocyte/macrophages are the source of IL-12, a key cytokine involved in the events that lead to formation of the psoriatic plaque. METHODS: Biopsy specimens were obtained from six patients with plaque psoriasis who were treated with 300 mg propylthiouracil (PTU) daily for three months. Clinical response to PTU as assessed by PASI scores, histological changes after treatment, and CD1a expression in lesional skin before and after treatment were studied. RESULTS: Despite significant improvement in clinical and histological parameters the expression of CD1a staining cells in the epidermis did not decline with propylthiouracil treatment. CONCLUSIONS: It appears that the beneficial effect of propylthiouracil in psoriasis is mediated by mechanisms other than by depletion of skin antigen-presenting cells.

Adult↗

Analysis of heterogeneity of atypia within melanocytic nevi.

BACKGROUND: Incisional biopsy of clinically atypical nevi continues to be a common practice. Questions can arise as to the adequacy of these partial biopsies. OBJECTIVE: To determine whether incisional (partial) biopsy specimens may be considered representative of the entire lesion, atypical nevi submitted to our dermatopathology laboratory were examined for the presence or absence of heterogeneity of atypia within the individual nevi. DESIGN: The study included 250 histologically atypical nevi that were selected consecutively from pigmented lesions that were submitted to our dermatopathology laboratory by community and academic dermatologists for histopathologic analysis. Also, 23 moderately to severely atypical and 25 severely atypical nevi from consecutive submissions were added for statistical reasons. Lesions with both clear and involved margins were used. Lesions were considered homogeneous if the atypia involved the entire lesion or heterogeneous if either the atypia was focal or if different degrees of atypia occurred within the same lesion. Atypia was defined by the usual parameters of architectural and cytologic atypia and host response. Also, the degree of atypia in relationship to heterogeneity and to patient age was determined. SETTING: The Dermatopathology Laboratory, University of California, Irvine. MAIN OUTCOME MEASURES: Outcome measures included the percentage of nevi exhibiting heterogeneity of atypia, heterogeneity of atypia in relation to patient age, degree of atypia in relation to patient age, and degree of atypia in relation to the presence of heterogeneity of atypia. RESULTS: Of the 298 nevi examined, 107 (35.9%) were heterogeneous in atypia and 191 (64.1%) were homogeneous in atypia. There was no significant difference in age between patients with heterogeneous lesions and those with homogeneous lesions. There was a statistically significant correlation between the degree of atypia and patient age. The average age of patients with a lesser degree of atypia was 36.9 years, while the average age of patients with a greater degree of atypia was 44.8 years (P<.005). There was no significant correlation between degree of atypia and heterogeneity of atypia (correlation coefficient, 0.1). CONCLUSIONS: A clinically significant proportion of atypical nevi exhibited heterogeneity of atypia. Also, there was a significant relationship between the degree of atypia and increasing age (P<.005). Therefore, if a clinically atypical nevus warrants a biopsy, these results give additional support for complete excisional biopsy (which can include shave or punch) to assure adequate histopathologic sampling of the lesion.

Adult↗

Chemoprevention of nonmelanoma skin cancer: experience with a polyphenol from green tea.

Nonmelanoma skin cancer is extremely common and is increasing in incidence. It would be very useful to have forms of therapy that would prevent precancerous changes from going on to form cancer, or to reverse the precancerous changes. Epidemiologic evidence in humans, in vitro studies on human cells, and clinical experiments in animals have identified polyphenol compounds found in tea to be possibly useful in reducing the incidence of various cancers, including skin cancer. To examine the potential for a polyphenol from green tea, epigallocatechin gallate, to act as a chemopreventive agent for nonmelanoma skin cancer, a randomized, double-blind, placebo-controlled phase II clinical trial of topical epigallocatechin gallate in the prevention of nonmelanoma skin cancer was performed.

Antineoplastic Agents, Phytogenic↗

Calcospherules associated with juvenile hyaline fibromatosis.

Juvenile hyaline fibromatosis is a rare autosomal recessive genodermatosis that manifests with 1 to 5 cm skin tumors, gingival hyperplasia, osteolytic bone lesions, and joint contractures. The skin tumors are most often located on the head and periarticular extremities. A case of juvenile hyaline fibromatosis with typical skin tumors that on biopsy exhibited basophilic calcospherules is presented. Although noted in a single case, these structures may be a novel, yet helpful, diagnostic marker.

Adult↗

Vesicular lesions in a patient with lipoid proteinosis: a probable acantholytic dermatosis.

Lipoid proteinosis is a rare genodermatosis with characteristic clinical and histologic findings later in life. We present a case of lipoid proteinosis in which the diagnosis was originally missed because the patient presented in childhood with vesicles and a hoarse voice and lacked any other manifestations. Microscopic examination of a vesicle revealed extensive non-dyskeratotic acantholysis. Vesiculo-bullous lesions have been described clinically in lipoid proteinosis, but we are unaware of any histopathologic description regarding bullae formation. Although only a single patient is herein described, it seems unlikely that this type of acantholysis is purely coincidental. It is proposed that lipoid proteinosis should be in the differential of acantholytic vesiculo-bullous lesions in a child.

Acantholysis↗

Ki-67 and p53 expression in minimal deviation melanomas as compared with other nevomelanocytic lesions.

Minimal deviation melanoma is a controversial entity encompassing a heterogeneous group of lesions cytologically in the spectrum between recognized subtypes of nevi and conventional "primary configuration" melanomas and reported to have a better prognosis than the latter. To evaluate the distinctiveness of minimal deviation melanoma, Ki-67 proliferation rates and p53 expression in minimal deviation melanomas were compared with those in compound nevi, Spitz nevi, and vertical growth phase superficial spreading malignant melanoma. Twelve examples of each lesion were immunostained with antibodies to the Ki-67 and p53 proteins and evaluated by a pathologist who was blind to the diagnoses. The mean Ki-67 (MIB-1) proliferation rates for the compound nevi, Spitz nevi, minimal deviation melanomas, and superficial spreading malignant melanomas were 0, 3%, 13%, and 25%, respectively. The mean Ki-67 proliferation rate was statistically greater in the minimal deviation melanomas than in the compound nevi or the Spitz nevi (P <.05), but the proliferation rates in the two melanoma subtypes were not statistically significant (P =.08). The mean p53 values for these lesions were 0, 9%, 9%, and 26%, respectively; the latter two were statistically different (P <.01). Based on these Ki-67 and p53 immunophenotypes, minimal deviation melanoma may represent a distinct entity.

Biomarkers, Tumor↗