Dogliotti and Phillips classifications are unsuitable for grading the histopathological findings of exogenous ochronosis.

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.

Intralymphatic histiocytosis in healing cellulitis: Case report and review of the literature.

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.

A pink enlarging plaque on the plantar foot: amelanotic acral lentiginous melanoma.

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.

Folliculin mutation-negative trichodiscomas in a patient with multiple endocine neoplasia type I syndrome.

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.

Clinical validation of a gene expression signature that differentiates benign nevi from malignant melanoma.

BACKGROUND: Histopathologic examination is sometimes inadequate for accurate and reproducible diagnosis of certain melanocytic neoplasms. As a result, more sophisticated and objective methods have been sought. The goal of this study was to identify a gene expression signature that reliably differentiated benign and malignant melanocytic lesions and evaluate its potential clinical applicability. Herein, we describe the development of a gene expression signature and its clinical validation using multiple independent cohorts of melanocytic lesions representing a broad spectrum of histopathologic subtypes. METHODS: Using quantitative reverse-transcription polymerase chain reaction (PCR) on a selected set of 23 differentially expressed genes, and by applying a threshold value and weighting algorithm, we developed a gene expression signature that produced a score that differentiated benign nevi from malignant melanomas. RESULTS: The gene expression signature classified melanocytic lesions as benign or malignant with a sensitivity of 89% and a specificity of 93% in a training cohort of 464 samples. The signature was validated in an independent clinical cohort of 437 samples, with a sensitivity of 90% and specificity of 91%. CONCLUSIONS: The performance, objectivity, reliability and minimal tissue requirements of this test suggest that it could have clinical application as an adjunct to histopathology in the diagnosis of melanocytic neoplasms.

Invasion risk of cutaneous squamous cell carcinoma in situ by histological subtype: a retrospective cohort study.

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.

Accuracy of biopsy sampling for subtyping basal cell carcinoma.

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.

A randomized, controlled trial of four ablative fractionated lasers for photoaging: a quadrant study.

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.

Livedo reticularis: a side effect of interferon therapy in a pediatric patient with melanoma.

Livedo reticularis is a lacy mottling of the skin that can have many etiologies. We report a case of an 8-year-old boy with a diagnosis of melanoma who developed persistent livedo reticularis during treatment with interferon alpha-2B. To our knowledge, this is the first case report of livedo reticularis occurring as a side effect of interferon treatment for pediatric melanoma. Given the increasing incidence of pediatric melanoma, it is important that dermatologists be aware of potential side effects of interferon therapy to optimize care and education for these patients.

Clonal-pattern Seborrheic Keratosis: Risk of Recurrence and Progression to Carcinoma.

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.

Changing Trends in Dermatopathology Case Complexity: A 9-Year Academic Center Experience.

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.

Low-affinity nerve growth factor receptor (P75 NGFR) as a marker of perineural invasion in malignant melanomas.

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.

Melanocytic nevi in pregnancy: histologic features and Ki-67 proliferation index.

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.

Effect of melanoma on immune function in the regional lymph node basin.

PURPOSE: To determine if melanoma within the tumor microenvironment will result in immunosuppression within the draining lymph node as measured by down-regulation of T-cell receptor zeta (TCR zeta) expression. EXPERIMENTAL DESIGN: Patients with clinical stage I to III melanoma undergoing wide local excision and sentinel lymph node biopsy or therapeutic lymph node dissection were consented to have a portion of their lymph node sampled. Lymph nodes were classified as macroscopically involved (TI), microscopically involved (MI), noninvolved with positive wide excision (NI+), or noninvolved with negative wide excision (NI-). Lymphocytes were stained using antibodies to TCR zeta and other immune cells and analyzed via flow cytometer. Reverse transcription-PCR was used to assess for mediators of immunosuppression. RESULTS: Fifty patient lymph node samples (15 TI, 7 MI, 9 NI+, and 19 NI-) were evaluated. Increasing involvement of tumor in the lymph node was associated with decreasing TCR zeta chain expression (TI 56%, MI 76%, and NI- 89%). Differences between TI and MI (P = 0.005), TI and NI- (P = 0.0001), and MI and NI- (P = 0.019) were statistically significant. There was also a significant difference between TCR zeta chain expression of NI+ and NI- (73% versus 89%; P = 0.0016). A trend toward increased arginase expression in tumor-involved lymph nodes was detected by reverse transcription-PCR. CONCLUSIONS: Melanoma involvement of regional nodes is associated with loss of TCR zeta expression that is inversely related to tumor burden. Residual melanoma within the wide local excision specimen is associated with TCR zeta loss in noninvolved sentinel lymph nodes, suggesting that immune modulation precedes tumor spread.

Imatinib-induced regression of AIDS-related Kaposi's sarcoma.

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.