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Background: Colloid bodies (CB), also known as Civatte bodies, are commonly seen in inflammatory dermatoses and are thought to represent cell degeneration. No studies have investigated the incidence and clinical associations of CB in cutaneous basal cell carcinoma (BCC). The aim of this study is to assess the incidence of CB in BCC lesions and analyze their clinical associations., Methods: Four hundred and five sequential cases of cutaneous BCC from 396 patients diagnosed from 1/1/2023 to 12/31/2023 in our institution were studied for the presence of CB. Only cases of BCC with a single growth pattern were included. BCC subtype, patient age, location of the lesion, history of previous BCC at other site, smoking history, and allergy history were collected. Cases with and without CB were compared for each parameter using the paired t-test for age and the Chi-square test for categorical data., Results: Patients were grouped based on the presence of CB into a study group (57 cases) and control group with no CB (348 cases). CB were identified in 14% (57/405) of BCCs. 19% (54/281) of nodular, 12.5% (1/8) of infiltrative, and 1.7% (2/116) of superficial type BCCs had CB. BCC with CB were more common on the face/scalp than other sites (66.7% vs. 34.2%, p < 0.001). Patients with CB were older (median 72 vs. 68 years ±12, p = 0.04), predominantly male (63% vs. 47%, p = 0.02), more frequently had a prior BCC (0.61% vs. 0.38%, p = 0.012), and did not differ in smoking history compared to the control cohort., Conclusions: We identified CB in 14% of BCCs studied, most commonly in nodular, followed by infiltrative, and least often superficial type. After cohort matching, significant clinical associations of CB in BCC were sun-exposed location and personal history of one or more prior BCC at other site(s). Their pathogenesis is not known, however their presence suggests tumor regression, which may potentially be exploited for new therapies in a subset of patients., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aims: Cutaneous squamous cell carcinoma in situ (SCCis) can be classified histopathologically into four subtypes: full-thickness (FT), hypertrophic actinic keratosis (HAK), Bowenoid, and acantholytic types. 3%-5% of SCCis lesions progress to invasive squamous cell carcinoma (iSCC), however progression risk by subtype has not been assessed. Aim one of this study is to quantitatively assess the risk of iSCC associated with each histological subtype of SCCis. Aim two is to evaluate if the histological grade of iSCC differs among subtypes of the associated SCCis., Methods: The pathology information system at our institution was queried for cutaneous SCCis cases with and without associated iSCC from 2020 to 2022. The study group consisted of 65 cases of SCCis with associated iSCC and control group 65 randomly selected cases of SCCis without invasion. For each case SCCis subtype was classified as FT, HAK, Bowenoid or acantholytic type. iSCCs were classified as low grade if well to moderately differentiated (LG) and high grade (HG) if moderately to poorly differentiated., Results: iSCC was most often associated with HAK-type SCCis, followed by acantholytic and FT-type SCCis, with Bowenoid type rarely associated with iSCC. 41% (14/34) of iSCCs associated with HAK-type SCCis were HG compared with 84% (21/25) for FT-type SCCis., Conclusions: iSCC is most often associated with HAK-type SCCis, followed by acantholytic and FT-types, and rarely with Bowenoid type. HG invasive SCC is most often associated with FT-type, and LG with HAK-type SCCis. Stratifying SCCis by subtype can inform clinical management., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Seborrheic keratosis is a benign epidermal tumor. Seborrheic keratosis with clonal pattern (CPSK) displays histologic features distinct from other subtypes of SK (non-CPSK). We sought to quantitatively assess the risk of recurrence and progression to squamous cell carcinoma (SCC), either in situ or invasive, of incompletely excised CPSKs. We studied all 244 cases from 238 patients of "seborrheic keratosis, clonal pattern" diagnosed in our institution over a 10-year period (2008-2018). Demographic, clinical, pathologic, and follow-up data were gleaned from electronic health records. Following glass slide review, CPSK lesions were divided into 2 groups: CPSK with cytologic atypia and CPSK without cytologic atypia. For comparison, 107 non-CPSKs were studied as controls. The minimum follow-up period was 2 years (median=4 y). All lesions were incompletely excised. Eighteen of 244 CPSKs (7.4%) recurred at or adjacent to the site of initial partial removal compared with 1.9% of non-CPSKs. Five of the 18 (28%) recurrent CPSKs recurred as CPSK, 11 (61%) as SCC in situ, and 3 (17%) as invasive SCC. The mean time to recurrence was 3.1 years. Two non-CPSKs recurred as non-CPSKs. Overall CPSKs were more likely to recur than non-CPSKs ( P =0.04). CPSKs with atypia were more likely to recur than CPSKs without atypia ( P =0.03). The upgrade rate to SCC at least in situ of all recurrent CPSK lesions with atypia was 78%. Our results suggest that pathologists should report the presence of clonal pattern when observed in seborrheic keratoses, indicate the presence of atypia, and provide lesional margin assessment., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Cutaneous exogenous ochronosis (EO) is frequently graded and staged according to the Dogliotti or Phillips classification system, both in research studies and in clinical practice. There are no data to support the use of these systems in either of these settings. These systems additionally purport that the clinical and histopathological findings of EO are concordant; however, anecdotal evidence suggests otherwise. We aimed to determine the clinical-histopathological concordance rates in EO and to assess the suitability of the Dogliotti and Phillips classification systems for the grading and staging of EO lesions., Methods: Five cutaneous EO cases diagnosed at our institution were studied. Clinical and histopathological data were obtained by medical record and histopathology slide review. Each case was assigned a clinical and histopathological grade according to both the Dogliotti and Phillips classifications. Clinical-histopathological concordance rates were determined for each classification., Results: Clinical-histopathological concordance was seen in 80% and 60% of EO lesions when graded according to the Dogliotti and Phillips classifications, respectively., Conclusions: Cutaneous EO lesions do not consistently show clinical-histopathological concordance. Although the Dogliotti and Phillips classifications may have clinical utility, they are not suitable to grade EO histopathologically., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Context.—: Pathology case volume and complexity impact clinical service burden, staffing, and reimbursement, particularly in an academic setting., Objective.—: To investigate dermatopathology case complexity by using indicators of challenging cases, which require increased clinical service effort., Design.—: A retrospective review was performed of dermatopathology cases during a 9-year period at a tertiary care academic center. A subset of cases was analyzed for which extractable data were available. Cases requiring the following metrics of complexity were identified: rush processing, consensus agreement, performance of immunohistochemistry, use of special histochemical stains, use of immunofluorescence, examination of additional tissue levels, review of a prior case, addition of an explanatory note, presence of multiple specimen parts, and use of intradepartmental consultation., Results.—: A total of 8173 cases were reviewed. During the same 3-month period of the year, there was a statistically significant increase in use of rush processing/interpretation, consensus review, number of cases requiring immunostains, special stains, levels, and an explanatory note, and cases reviewed by other subspecialists in the department from 2010 to 2019., Conclusions.—: This study shows an increasing trend in dermatopathology case complexity, suggesting that overall clinical service efforts have increased. These findings may inform clinical service staffing and reimbursement.

Intralymphatic histiocytosis (ILH) is a rare skin benign condition observed in a variety of inflammatory settings. It is characterized by the presence of ectatic dermal lymphatic vessels containing aggregates of histiocytes. Associated conditions that have been identified include rheumatoid arthritis, metallic orthopedic implants, inflammatory bowel disease, and malignancies of the breast, skin, and colon. Some cases with no attributable underlying cause have been described. The pathophysiology of ILH is not well understood. It has been proposed that it may represent macrophage migration during immune activation. Herein, we present the first description of ILH observed in the healing phase of cellulitis on the skin of the breast. Awareness of this possibility is important when the diagnosis of intravascular carcinomatosis is being considered., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Acral lentiginous melanomas account for less than 5% of all melanomas, whereas amelanotic melanomas account for around 2-8% of all melanomas. Amelanotic acral lentiginous melanomas are even less common and can often be mistaken for other clinical entities, including pyogenic granulomas, non-melanoma skin cancers, and warts. We describe a man in his 50s with a twenty-year history of a skin-colored plaque on the right plantar foot; after enlargement and failure of wart treatment, a shave biopsy revealed an amelanotic melanoma. A subsequent wide local excision and sentinel lymph node biopsy revealed melanoma in 4 lymph nodes and the patient underwent an abbreviated course of interferon-alpha therapy. The patient remained stable until 2 ? years after diagnosis, at which time he presented with in-transit metastases on the foot and right thigh; he has since been stable on nivolumab. This case represents the challenge of diagnosing amelanotic melanomas on acral surfaces and highlights the importance of considering a skin biopsy for diagnosis of any changing, atypical amelanotic lesions on the feet or hands.

Mycosis fungoides (MF) is the most common cutaneous T cell lymphoma that involves the oral mucosal. The manifestation of lesions within the oral cavity generally correlates with a poor prognosis. Management of MF includes skin directed therapies and localized radiation treatment, with systemic biologic therapies and chemotherapy used for more advanced stages. The clinical and histologic features of MF in a patient with oral disease are reviewed.

Coxiella burnetii is a rare cause of chronic infection that most frequently presents as endocarditis. We report a case of C burnetii causing an infected abdominal aortic aneurysm with contiguous lumbar osteomyelitis resulting in spinal cord compromise. The diagnosis was established by serologic studies consistent with chronic Q-fever (ratio of C burnetii immunoglobulin [Ig]G phase II titer to IgG phase I titer <1) and was confirmed by positive C burnetii polymerase chain reaction of vertebral tissue in addition to pathology of vertebral bone showing intracellular Gram-negative coccobacillary bacteria. The patient clinically improved after surgical decompression and prolonged treatment with doxycycline and hydroxychloroquine.

Importance: Targeted BRAF inhibitor therapy (vemurafenib, dabrafenib) is an effective, novel treatment for patients with metastatic melanoma with the V600E BRAF mutation. This therapy is associated with squamous cell carcinomas and keratoacanthomas. Granulomatous eruptions have not been previously reported., Observations: Two patients with melanoma developed cutaneous granulomatous eruptions during targeted BRAF inhibitor therapy. In case 1, after 2 months of treatment with dabrafenib and trametinib (MEK inhibitor), a papular eruption concerning for progression of disease prompted cessation of treatment. After the histopathologic diagnosis of granulomas, the patient was treated with clobetasol ointment with resolution within days and resumption of therapy. In case 2, after 5 months of vemurafenib treatment, the patient developed a granulomatous eruption, which resolved 3 weeks after cessation of therapy., Conclusions and Relevance: We report 2 cases of cutaneous granulomatous eruptions on treatment with targeted BRAF inhibitors, a previously unreported association. Although additional investigations are necessary to better elucidate the pathogenic mechanisms, our report includes a treatment plan that prevents unnecessary discontinuation of therapy. Given the Food and Drug Administration approval of vemurafenib for metastatic melanoma, clinicians should be aware of this possible cutaneous reaction and treatment option to optimize patient management.

Objective: To evaluate the incidence, type, and severity of telaprevir-associated skin reactions., Design: Three dermatologists assessed available information including photographs, biopsy results, and clinical summaries of all cases with skin eruptions reported as moderate or severe during the telaprevir clinical development program. For cases from placebo-controlled trials, they were masked to exposure., Settings: Phase 1 to 3 studies of telaprevir combination therapy for hepatitis C., Patients: All patients with skin eruptions enrolled in telaprevir clinical trials prior to 2011 MAIN OUTCOME MEASURES: Incidence, diagnosis, morphologic features, extent, and severity of skin eruption., Results: Skin eruptions were more frequent in patients who received telaprevir as part of hepatitis C treatment compared with pegylated interferon (peginterferon) and ribavirin alone (56% vs 34% overall; 3.7% vs 0.4% severe). Occurring at any time during the 12 weeks of telaprevir combination regimen, in more than 90% of cases, this eruption is pruritic eczematous dermatitis. None of the clinical or genetic factors examined were substantial risk factors for dermatitis. Three cases of Stevens-Johnson Syndrome (SJS), and 11 cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) were suspected, with 2 SJS and 3 DRESS cases considered likely., Conclusions: Telaprevir-related dermatitis occurs in a majority of telaprevir-treated patients. It is an eczematous dermatitis that differs in timing and appearance from the eruptions usually associated with drug reactions. The strong signal for an increased risk of DRESS or SJS requires particular vigilance in telaprevir-treated patients.

Background: Fractionated technology has revolutionized laser therapy. With the success of initial devices, several fractionated lasers have appeared on the market. Claims of superiority have made device choice difficult for physicians and patients., Materials and Methods: Twelve subjects were treated with fractionated ablative lasers (10,600-nm carbon dioxide and 2790-nm yttrium scandium gallium garnet) in this institutional review board-approved trial. Each face was divided into four quadrants, and each quadrant was randomly treated using one of four lasers. Clinical experience was used to optimize settings. Two patients submitted biopsies from each quadrant immediately after treatment. Patients and blinded investigators assessed pain during treatment and post-treatment improvement in photoaging (measured by rhytides, lentigines, texture, and pore size) using a five-point scale., Results: All devices resulted in statistical improvement in photoaging in all patients, but no device was statistically significantly superior. No statistically significant difference was found in pain scores. All patients reported satisfaction 1 month after treatment. Three patients experienced adverse reactions. Histologically, there were no statistically significant differences between devices., Conclusions: Fractionated ablative lasers reliably result in improvement in photoaging. Despite marketing claims, no statistically significant differences were found in outcomes, pain during treatment, or histologic findings. Even with experienced users, significant adverse reactions are possible., (© 2012 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.)

Background: Basal cell carcinoma (BCC) is a common skin cancer for which the treatment and recurrence risk correlate with the histologic subtype. Limited information is available regarding the accuracy of biopsy in diagnosing BCC subtypes., Objective: We sought to determine the correlation between BCC subtypes present in a biopsy specimen and the actual subtypes present in a tumor., Methods: In this retrospective study, skin biopsy specimens and corresponding excisions were reviewed. All histologic subtypes present in the biopsy specimen were reported and compared with the composite BCC subtype present in the biopsy specimen and excision., Results: A total of 232 biopsy specimens and corresponding wide excisions were examined. The biopsy specimen accuracy rate was 82% for punch and shave biopsy specimens. Mixed histologic subtypes were seen in 54% of the cases, half of which contained an aggressive subtype (infiltrative, morpheaform, or micronodular). There was an 18% discordance rate between the biopsy specimen subtype and the composite subtype. Importantly, 40% of these discordant cases (7% of all cases examined) had an aggressive subtype that was not sampled in the initial biopsy specimen. Furthermore, some cases were misidentified as infiltrative subtype in the biopsy specimen as a result of misinterpretation of surface ulceration and reactive stromal changes., Limitations: The limited number of punch biopsy specimens and the fact that Mohs excisions were not included are limitations., Conclusions: Punch and shave biopsy specimens provided adequate sampling for correct BCC subtyping in 82% of the cases examined. However, 18% of the biopsy specimens were misidentified, some of which missed an aggressive component. Thus, there are potential pitfalls in the identification of BCC subtypes in biopsy specimens, which may have important implications in treatment outcome., (Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Keloid scarring is a consequence of aberrant wound healing that leads to expansion of the scar beyond the confines of the skin injury. Keloid scars are characterized by excessive extracellular matrix disposition, prolonged proliferation of fibroblasts, increased angiogenesis, and inflammatory cell infiltration. There is no single satisfactory treatment for keloid, and it can lead to severe disfigurements and bodily dysfunction. Thus, clarification of the mechanisms underlying keloid formation, as well as those that prevent it from behaving as a malignant tumor, has significant consequences not only for treatment of keloid but also for the prevention of malignant tumor formation. Senescence is an irreversible form of growth arrest that has been shown to play a role, both in vitro and in vivo, in preventing malignant tumorigenesis upon oncogenic stress. In this study it is shown that fibroblasts embedded inside keloid scars proliferate at a slower rate compared with either those residing at the proliferative edges of the scar or normal fibroblasts. Likewise it is demonstrated that keloid fibroblasts exhibit a cell-cycle arrest with a G2/M DNA content and a higher rate of senescence. The results also indicate that levels of the tumor suppressor protein PML are higher in the active regions of keloid. The study therefore suggests that senescence is one possible mechanism by which keloid is maintained in a benign state. On this basis, "pro-senescence therapy" should be taken into consideration when designing treatment strategies for keloid.

Background: Changes in the clinical appearance of benign dermal nevi during pregnancy may be concerning for malignant transformation. Because the hormonal milieu of pregnancy has not proven to alter their banal behavior, histologic characterization is needed to prevent over-diagnosis and unnecessary treatment., Methods: Dermal nevi excised from pregnant women (n = 16) were compared with nevi from location- and aged-matched control patients (n = 15). Histologic features and Ki-67 proliferation index were evaluated., Results: Nevi in pregnancy were more likely to have dermal mitotic figures (62.5% vs. 13.3%, p = 0.028) and higher mitotic rates (1.44 vs. 0.20 mitoses/mm(2), p = 0.0027) than control nevi. A distinctive histologic entity, termed superficial micronodules of pregnancy (SMOPs), was observed more frequently in the nevi of pregnancy (81.3% vs. 26.7%, p = 0.040), and showed consistent immunoreactivity for HMB45. There was a trend toward higher Ki-67 proliferation index in the nevi of pregnancy (3.0% vs. 1.0%, p = 0.073). Prominent multinucleated melanocytes were seen only in controls. There was no significant difference in pigmentation or irritation changes between groups., Conclusions: Dermal nevi removed during pregnancy show characteristic histologic features including increased dermal mitoses, superficial micronodules of pregnancy (SMOPs), and trend toward increased Ki-67 proliferation index.

Background: Perineural invasion (PNI) is a well-recognized route of tumor extension in cutaneous neoplasms. Despite an established association with increased local recurrences and metastases, the mechanisms responsible for PNI have yet to be elucidated. We hypothesize that P75 NGFR, a nerve growth factor receptor, may be implicated in the pathogenesis of PNI in these tumors., Methods: P75 NGFR immunohistochemical staining was performed on 47 skin tumors with PNI including invasive squamous cell carcinomas (SCCs = 29), basal cell carcinomas (BCCs = 8) and malignant melanomas (MMs = 10). These were compared with similar lesions without PNI (SCCs = 7, BCCs = 7 and MMs = 9)., Results: P75 NGFR staining was absent in all invasive SCCs irrespective of the presence of PNI (n = 0/36). Two BCCs with PNI (n = 2/8) and three without PNI (n = 3/7) showed focal P75 NGFR staining. Interestingly, 8 of 10 invasive MMs with PNI had positive P75 NGFR expression (80%), in contrast to only 1 of 9 without PNI (11%)., Conclusions: P75 NGFR may play a mechanistic role in invasive MMs demonstrating PNI. Furthermore, its expression may serve as a marker of PNI in those tumors that lack histological evidence of nerve involvement at the time of excision.

Previous studies in rodents and people have demonstrated that repeated tick exposure is associated with reduced Borrelia burgdorferi transmission but the mechanism of prevention remains unclear. We examined the acute histopathologic reactions to initial and repeated Ixodes scapularis bites in BALB/c mice and in people. Skin biopsies of BALB/c mice infested for the first time by I. scapularis nymphs revealed vascular dilatation and an accumulation of inflammatory cells adjacent to the bite site but absent at the site of tick attachment. Such changes would enhance tick-borne pathogen transmission. Mice reexposed to I. scapularis nymphs experienced a decrease in vascular dilatation and a marked increase in inflammatory cells at the site of tick attachment. Skin biopsies of people with attached I. scapularis nymphs revealed similar histologic patterns. These results indicate that cellular changes at the tick-dermal interface following I. scapularis attachment are likely to allow for successful transmission of tick-borne pathogens in non-tick-immune hosts and to inhibit tick-borne pathogen transmission in hosts that have developed tick immunity.

The potential role of stem cells in neoplasia is a subject of recent interest. Three markers of melanocytic stem cells have been described recently. CD166 is expressed on the surface of mesenchymal stem cells and has been found on human melanoma cell lines. CD133 is expressed on the surface of dermal-derived stem cells that are capable of differentiating into neural cells. Nestin is an intermediate filament expressed in the cytoplasm of neuroepithelial stem cells. In this study, we evaluate the expression of these markers and possible differences among banal nevi, primary melanoma, and metastastic melanoma. Tissue microarrays containing normal tissue and 226 melanocytic lesions (71 banal nevi, 71 in situ and invasive melanomas, and 84 metastatic melanomas) were studied by immunohistochemistry using monoclonal antibodies CD166, CD133, and nestin. A significantly greater percentage of melanomas (combined primary and metastatic) contained cells that expressed CD166 (P=0.005), CD133 (P=0.003), and nestin (P=0.03) than banal nevi. Only nestin showed a statistical difference when comparing primary and metastatic melanoma (P=0.05). A stepwise increase in the proportion of lesions expressing all three markers was observed from banal nevi (2/19) to primary melanomas (8/17) to metastatic melanoma (19/28), P=0.0005. All cases of metastatic melanoma expressed at least one stem cell marker. The increased expression of CD166, CD133, and nestin in melanoma suggests that progression to malignant melanoma likely involves genetic pathways instrumental to stem cell biology and normal tissue development. Further studies and characterization of these pathways may also reveal new prognostic markers for a disease whose prognosis in advanced stages is dismal.

Background: Matrix metalloproteinases (MMPs) are associated with Kaposi's sarcoma (KS) tumorigenesis. To date, only a few MMPs have been studied in KS lesions. Their role in KS regression has not been investigated. The aim of this study was to evaluate the expression of multiple MMPs in developing and pharmacologically regressed KS lesions., Methods: Nine samples of acquired immune deficiency syndrome (AIDS)-related and classic cutaneous KS lesions at various histological stages were studied. Regressing KS lesions from three patients treated with systemic therapy were procured after one and two cycles of chemotherapy. Tissue sections from all specimens were immunostained using monoclonal antibodies to MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-13, and MMP-14., Results: KS lesional cells were immunoreactive for all MMPs, except MMP-14. Admixed inflammatory cells were immunoreactive for MMP-1, MMP-2, MMP-7, MMP-9, and MMP-13. The MMP immunoprofile in residual KS lesional cells was unaltered in regressed lesions. Increased extracellular matrix (ECM) and macrophage immunoreactivity for MMPs was identified in regressed specimens., Conclusions: These data show that developing KS lesional cells express collagenases (MMP-1, MMP-13), gelatinases (MMP-2, MMP-9), stromelysin-1 (MMP-3), and matrilysin (MMP-7) but not the membrane-type MMP-14. This MMP expression profile is retained by residual KS cells and also expressed by infiltrating macrophages in regressed KS lesions. Pantanowitz L, Dezube BJ, Hernandez-Barrantes S, Tahan SR, Dabbous MK. Matrix metalloproteinases in the progression and regression of Kaposi's sarcoma.

Kaposi sarcoma (KS) is a multicentric vascular neoplasm characterized histologically by the progressive proliferation of spindle-shaped tumor cells in all epidemiologic (AIDS-related, classic, endemic, and iatrogenic) forms. Human herpesvirus 8 (HHV8) is associated with all epidemiologic forms of KS and has been shown in vitro to induce the tyrosine receptor kinase c-kit in HHV8-infected cells. To date, c-kit immunoreactivity has not been systematically studied in KS lesions. Therefore, the aim of this study was to evaluate c-kit expression by immunohistochemistry in different proliferative stages and epidemiologic forms of KS. Archival cases of formalin-fixed, paraffin-embedded KS lesions, including 9 classic, 11 AIDS-related, and 15 African (endemic) forms at various histologic stages (5 patch, 8 plaque, 22 nodular), biopsied from different sites, were stained using immunohistochemistry with antibodies to HHV8 (LNA-1) and c-kit (CD117). C-kit immunoreactivity of lesional cells was demonstrated in 15 (43%) cases overall. A total of five (56%) classic, five (45%) AIDS-related, and five (33%) endemic KS cases were positive for c-kit. There was no difference in the intensity of c-kit staining between the different epidemiologic groups and histologic stages of KS. HHV8 (LNA-1) immunoreactivity was present in all (100%) classic, 10 (91%) AIDS-related, and 9 (60%) endemic cases. LNA-1 staining was demonstrated in 13 (93%) of the c-kit-positive and 15 (75%) of the c-kit-negative KS lesions. These findings indicate that c-kit expression in lesional cells can be detected by immunohistochemistry in different epidemiologic forms and histologic stages of KS. Furthermore, the expression of c-kit does not correspond with the presence of HHV8 (LNA-1) immunoreactivity in KS lesions.

Purpose: Activation of the platelet-derived growth factor (PDGF) and c-kit receptors has been proposed as important in mediating the growth of AIDS-related Kaposi's sarcoma (KS). We investigated the response of KS to the PDGF receptor (PDGFR)/c-kit inhibitor, imatinib mesylate, and investigated the effect of this therapy on critical signal transduction intermediates., Patients and Methods: Ten male patients with AIDS-related cutaneous KS, which progressed despite chemotherapy and/or highly active antiretroviral therapy, received imatinib mesylate administered orally, 300 mg twice daily. Clinical response was determined by serial tumor measurements. To determine biologic and histologic response, skin lesion biopsies were obtained at baseline and following 4 weeks of therapy., Results: Five of 10 participants had a partial response by tumor measurements. Biopsies after 4 weeks of therapy demonstrated histologic regression in four of six patients. Four patients' tumor biopsies were assessable for immunohistochemistry end points pre- and post-therapy. These demonstrated inhibition of PDGFR and its downstream effector, extracellular receptor kinase, which is a member of the mitogen-activated protein kinase family. The most common adverse event was diarrhea, which led to dose reduction in six patients., Conclusion: Imatinib mesylate administered orally twice daily for AIDS-related KS results in clinical and histologic regression of cutaneous KS lesions within 4 weeks. These promising results demonstrate that inhibition of the c-kit and/or PDGF receptors may represent an effective strategy for treating KS.

Background: Melanomas with poorly defined borders, lack of pigmentation, lentiginous extension, and location in cosmetically sensitive regions represent diagnostic and therapeutic challenges. Repeated surgical reexcisions are frequently required to achieve tumor-free margins. The use of reflectance mode confocal microscopy as an noninvasive method has shown to be a promising tool for diagnosing pigmented lesions in vivo., Observations: We report 3 clinical cases of melanoma: amelanotic melanoma (case 1), locally recurrent melanoma (case 2), and lentigo maligna melanoma (case 3). In case 1, in vivo confocal microscopy was instrumental in making the diagnosis and in monitoring the response to imiquimod therapy for in situ residual disease. It was also used to successfully delineate preoperative surgical margins in cases 2 and 3., Conclusion: As new methods for treating melanoma emerge and become more available, confocal microscopy can play a significant role by improving sensitivity in diagnosis, by increasing rates of successful initial excision, and by serving as a noninvasive means of monitoring therapy.

A case of beta-lactam antibiotic-induced pseudoporphyria is presented. A 24-year-old African American woman with systemic lupus erythematosus and end-stage renal disease on hemodialysis developed tense bullae on her forehead and cheeks after exposure to ampicillin-sulbactam and cefepime. Histologically, the lesions were similar to porphyria cutanea tarda, but without the associated porphyrin abnormalities. The lesions resolved spontaneously on cessation of the antibiotics.

Background: Kaposi's sarcoma (KS) is an angioproliferative lesion that may regress or progress. Progression is related to spindle cell proliferation and the expression of human herpes virus-8 latency genes, including latent nuclear antigen-1 (LNA-1), cyclin-D1, and bcl-2. KS regression has not been well characterized histologically. Therefore, this study was undertaken to characterize the histopathology of pharmacologically induced regressed cutaneous KS., Methods: Skin punch biopsies from eight patients with acquired immunodeficiency syndrome (AIDS)-related KS, that regressed following chemotherapy with paclitaxel or the angiogenesis inhibitor Col-3, were investigated by light microscopy. Comparative immunophenotyping on pre- and post-treatment specimens for CD31, LNA-1, cyclin-D1, bcl-2, and CD117 (c-kit) was performed., Results: Clinical and histologic features of regression were similar for paclitaxel and Col-3 treatment. On clinical examination, lesions flattened, became smaller, and lost their purple-red appearance, resulting in an orange-brown macule. Histological regression was divided into partial (n = 3) and complete (n = 5) regression. Partially regressed lesions had a significant reduction of spindle cells in the dermal interstitium, with residual spindle cells arranged around superficial and mid-dermal capillaries. Complete regression was characterized by an absence of detectable spindle cells, with a slight increase in capillaries of the superficial plexus. All regressed samples exhibited a prominent, superficial, perivascular, lymphocytic infiltrate and abundant dermal hemosiderin-laden macrophages. This clinicopathologic picture resembled the findings of pigmented purpura. CD31 staining correlated with the reduction of spindle cells. Regression was accompanied by a quantitative and qualitative decrease in LNA-1 and cyclin-D1 immunoreactivity, but no change in bcl-2 or c-kit expression., Conclusions: Pharmacologically induced regression of AIDS-related cutaneous KS is characterized by a complete loss or decrease of spindle cells, increased lymphocytes, and prominent dermal siderophage deposition. Without any prior knowledge of the history of KS regression following therapy, regressed KS lesions may be misdiagnosed clinically and histologically as pigmented purpuric dermatitis.

Background: Neurotrophins (NTs) are growth factors for neurons and other neural crest-derived cells. Their functions are mediated by 75-kDa low-affinity glycoprotein receptor (p75) NT receptor and a family of tyrosine kinase receptors (Trks) that includes Trk-A, -B, and -C. Signal transduction through the Trk receptors has been shown to regulate growth and apoptosis of tumors of neuronal origin. In addition, Trk oncogenes have been shown to be rearranged in some non-neuronal neoplasms. Recently, immunoexpression of NT-3 has been shown to be significantly higher in melanomas than in banal nevi on cryostat tissue., Methods: Since the biologic function of NT-3 is mediated primarily through Trk-C, we investigated Trk-C immunoexpression on paraffin sections of 10 compound nevi and 63 melanomas., Results: The expression of Trk-C was relatively low in compound nevi (30%). Trk-C expression was overall 62% in melanomas of various stages. Our data show that the expression of Trk-C increased as melanoma progressed from in situ (58%) to papillary dermal invasion (91%), and then declined in deeper (57%) and metastatic melanomas (31%)., Conclusion: These findings suggest a possible role of Trk-C in the progression of early stages of melanoma.

Extramammary fibroadenomas have been previously reported to mainly occur in the anogenital region, arising from mammary-like glands. The present report describes a 45-year-old woman who presented with a fibroadenoma of her eyelid that was associated with a cystadenoma. To our knowledge, this is the first case report of a fibroadenoma of the eyelid. The differential diagnosis and histogenesis of this lesion are discussed, and the literature pertaining to cutaneous fibroadenomas arising outside the breast is reviewed.

It has previously been reported that interferon alfa injection sites may develop pyoderma gangrenosum, interface dermatitis, vasculitis, or, more commonly, ulcers characterized by intravascular thrombi and a mixed inflammatory cell infiltrate. We describe 2 patients in whom granulomatous and suppurative dermatitis developed at interferon alfa injection sites. These cases extend the spectrum of interferon alfa injection site reactions. The histologic and clinical similarities of these cases with pyoderma gangrenosum and cutaneous Crohn's disease are explored.

It has been claimed that pyoderma gangrenosum (PG) lesions may contain granulomatous foci when associated with Crohn's disease. To test this assertion, we obtained clinical histories and archived cutaneous biopsies from 34 PG patients. Thirteen of these patients had inflammatory bowel disease (IBD). Immunostaining with PGM1, a macrophage marker, revealed well-formed giant cells with three or more nuclei in biopsies from 6 of 13 patients with IBD. Five of the 6 biopsies came from patients with Crohn's disease and one from a patient with ulcerative colitis. Two were peristomal. In the 21 patients who had PG without IBD, no giant cells were seen. Thus, PGM1+ histiocytic giant cells within a PG lesion may be indicative of associated IBD (p = 0.006), particularly Crohn's disease.

Although recurrence of viral hepatitis in liver transplants is common, data comparing recurrent hepatitis B (HB), hepatitis C (HC), and co-existing dual hepatitis B and C (HB&C) are sparse. Posttransplantation liver biopsies, along with molecular, serological, immunohistochemical, and clinical data from 27 patients with pretransplantation diagnosis of chronic viral hepatitis, were reviewed. The patients were placed into 4 groups: Group I, with pretransplantation HB (n = 8); group II, with pretransplantation HC (n = 10); group III with pretransplantation HC and anti-HB surface or core antibody (n = 4); and group IV, with pretransplantation HB&C (n = 5). The histopathologic findings and patient outcome were compared in the 4 groups. A high rate of recurrence of viral hepatitis was seen for all 4 groups: Group I = 100%, group II = 90%, Group III = 100%, and group IV = 80%, with the mean (median) recurrence time of 308 (224), 82 (52), 61 (64), and 125 (70) days, respectively. The number of deaths (their median survival times) were: group I = 4 (374 days), group II = 4 (794 days), group III = 1 (1,143 days), and group IV = 5 (448 days). The earliest histological findings of lobular injury was the presence of acidophil bodies and Kupffer cell hyperplasia, the latter being more prominent in recurrent HC cases. Recurrent HB presented in 2 forms: early (before 150 days) with poor survival and with either severe necroinflammatory histology or with features of fibrosing cholestatic hepatitis, and delayed (after 150 days), with mild necro-inflammatory activity and prolonged survival. HC with or without anti-HB antibodies had early recurrence, but the course was slowly progressive. Patients with HB&C had recurrence of both viruses; however, the course was dictated by HB virus.

Inflammatory stimuli and lipid peroxidation activate nuclear factor kappa B (NF-kappaB) and upregulate proinflammatory cytokines and chemokines. The present study evaluated the relationship between pathological liver injury, endotoxemia, lipid peroxidation, and NF-kappaB activation and imbalance between pro- and anti-inflammatory cytokines. Rats (5 per group) were fed ethanol and a diet containing saturated fat, palm oil, corn oil, or fish oil by intragastric infusion. Dextrose isocalorically replaced ethanol in control rats. Pathological analysis was performed and measurements of endotoxin were taken, lipid peroxidation, NF-kappaB, and messenger RNA (mRNA) levels of proinflammatory cytokines (tumor necrosis factor-alpha [TNFalpha], interleukin-1 beta [IL-1beta], interferon-gamma, [IFN-gamma], and IL-12), C-C chemokines (regulated upon activation, normal T cell expressed and secreted [RANTES], monocyte chemotactic protein [MCP]-1, macrophage inflammatory protein [MIP]-1alpha), C-X-C chemokines (cytokine induced neutrophil chemoattractant (CINC), MIP-2, IP-10, and epithelial neutrophil activating protein [ENA]-78), and anti-inflammatory cytokines (IL-10, IL-4, and IL-13). Activation of NF-kappaB and increased expression of proinflammatory cytokines C-C and C-X-C chemokines was seen in the rats exhibiting necroinflammatory injury (fish oil-ethanol [FE] and corn oil-ethanol[CE]). These groups also had the highest levels of endotoxin and lipid peroxidation. Levels of IL-10 and IL-4 mRNA were lower in the group exhibiting inflammatory liver injury. Thus, activation of NF-kappaB occurs in the presence of proinflammatory stimuli and results in increased expression of proinflammatory cytokines and chemokines. The Kupffer cell is probably the major cell type showing activation of NF-kappaB although the contribution of endothelial cells and hepatocytes cannot be excluded. Downregulation of anti-inflammatory cytokines may additionally exacerbate liver injury.

Previous work has suggested a key role of dendritic cells in antineoplastic immunity. The course of mycosis fungoides and cancers of the lung, colon, thyroid and stomach has been associated with dendritic cell response to the primary tumor. However, this has not been reported for cutaneous or mucosal squamous cell carcinoma (SCC). Thirty-six cases of primary SCC of the lip mucosa or vermillion border, including nine cases with regional metastasis, were studied to investigate the relationship of dendritic cell density with age, tumor grade, mitotic rate, diameter, ulceration, depth of invasion, muscle invasion, tumor-infiltrating lymphocytes (TILs) and metastasis. Dendritic cells were identified using S100 immunohistochemistry, and their peritumor and intratumor density (peri-S100D and intra-S100D) were determined. The mean peri-S100D was 314 +/- 50/mm2. High peri-S100D was associated with lower rate of metastasis (P = 0.03), and no case with peri-S100D > 311/mm2 metastasized. Peri-S100D inversely correlated with depth of invasion (P = 0.04) and ulceration (P = 0.02), and positively associated with TILs (P = 0.02). The mean intra-S100D was 317 +/- 42/mm2. Intra-S100D did not quantitatively correlate with metastasis; however, no metastasis occurred when intra-S100D exceeded 515/mm2. Intra-S100D correlated with brisk TILs (P = 0.04). These results suggest a functional role of dendritic cells in the immune response to SCC. Peri-S100D may be a prognostic indicator.

Protothecosis of subcutaneous and soft tissues is a rare occurrence in humans. We present two patients with chronic subcutaneous protothecosis affecting the elbow and foot respectively. Both patients had been treated with local corticosteroid injections and had recent exposure to water. The diagnosis was made histopathologically in both cases and confirmed by culture in one case. Histopathology showed typical Protothecal sporangia with surrounding mixed inflammatory infiltrate including necrotizing granulomas. Organisms stained positively with periodic acid-schiff, Gomori's methenamine silver, and Gridley fungus stains. In one case, intravenous chemotherapy was required to eliminate the pathogens. Histopathologic identification of the organisms is vital to ensure adequate therapy and avoid chronic smoldering infection.