Diagnostic discordance among histopathological reviewers of melanocytic lesions.

BACKGROUND: Histopathological examination is adequate for the diagnosis of most cutaneous melanocytic neoplasms. However, there is a subset that is either difficult to definitively diagnose or would have diagnostic disagreement upon review by multiple dermatopathologists if a more exhaustive review was performed. METHODS: Melanocytic lesions underwent an independent, blinded diagnostic histopathological review of hematoxylin and eosin-stained sections. Each lesion was reviewed by three to six dermatopathologists and categorized as benign, malignant, or unknown malignant potential (UMP). Diagnoses were grouped as concordant (all the same designation); opposing (received benign and malignant designations); majority (single designation with the highest number of diagnoses, no benign/malignant opposing designations); and non-definitive (equal number of non-opposing designations [i.e., benign/UMP or malignant/UMP]). Lesions with equivocal designations (concordant or majority UMP, opposing, majority, and non-definitive) were utilized in a patient treatment model of projected surgical treatment discrepancies. RESULTS: In total, 3317 cases were reviewed, and 23.8% of lesions received equivocal diagnoses. Of these, 7.3% were majority benign, 4.8% were majority malignant, 2.7% were majority UMP, 0.5% were concordant UMP, 6.9% were opposing, and 1.6% were non-definitive. Patient treatment models of those with equivocal lesions (n = 788) revealed a potential of overall surgical treatment variations ranging from 18% to 72%, with the highest variation amongst lesions with opposing, non-definitive, or majority UMP (40%-72%) diagnoses. CONCLUSION: Histopathologic review in this large cohort demonstrated substantial diagnostic variation, with 23.8% of cases receiving equivocal diagnoses. We identified diagnostic ambiguity even in lesions where a definitive diagnosis was previously rendered by a single real-world dermatopathologist. The combined clinical impact of diagnostic discordance or a final diagnosis of UMP is highlighted by high diagnosis-dependent treatment variation in the patient treatment model, which could be underreported in a real-world setting, where review by more than one to two dermatopathologists is relatively rare.

Neuroleptic strategies for terminal agitation in patients with cancer and delirium at an acute palliative care unit: a single-centre, double-blind, parallel-group, randomised trial.

BACKGROUND: The role of neuroleptics for terminal agitated delirium is controversial. We assessed the effect of three neuroleptic strategies on refractory agitation in patients with cancer with terminal delirium. METHODS: In this single-centre, double-blind, parallel-group, randomised trial, patients with advanced cancer, aged at least 18 years, admitted to the palliative and supportive care unit at the University of Texas MD Anderson Cancer Center (Houston, TX, USA), with refractory agitation, despite low-dose haloperidol, were randomly assigned to receive intravenous haloperidol dose escalation at 2 mg every 4 h, neuroleptic rotation with chlorpromazine at 25 mg every 4 h, or combined haloperidol at 1 mg and chlorpromazine at 12·5 mg every 4 h, until death or discharge. Rescue doses identical to the scheduled doses were administered at inception, and then hourly as needed. Permuted block randomisation (block size six; 1:1:1) was done, stratified by baseline Richmond Agitation Sedation Scale (RASS) scores. Research staff, clinicians, patients, and caregivers were masked to group assignment. The primary outcome was change in RASS score from time 0 to 24 h. Comparisons among group were done by modified intention-to-treat analysis. This completed study is registered with ClinicalTrials.gov, NCT03021486. FINDINGS: Between July 5, 2017, and July 1, 2019, 998 patients were screened for eligibility, with 68 being enrolled and randomly assigned to treatment; 45 received the masked study interventions (escalation n=15, rotation n=16, combination n=14). RASS score decreased significantly within 30 min and remained low at 24 h in the escalation group (n=10, mean RASS score change between 0 h and 24 h -3·6 [95% CI -5·0 to -2·2]), rotation group (n=11, -3·3 [-4·4 to -2·2]), and combination group (n=10, -3·0 [-4·6 to -1·4]), with no difference among groups (p=0·71). The most common serious toxicity was hypotension (escalation n=6 [40%], rotation n=5 [31%], combination n=3 [21%]); there were no treatment-related deaths. INTERPRETATION: Our data provide preliminary evidence that the three strategies of neuroleptics might reduce agitation in patients with terminal agitation. These findings are in the context of the single-centre design, small sample size, and lack of a placebo-only group. FUNDING: National Institute of Nursing Research.

Multiple melanocytic nevi restricted to mycosis fungoides patches in pediatric and young-adult patients. The potential role of local immunosuppression.

We described the development of multiple melanocytic nevi within long-standing MF patches in four young patients. Mycosis fungoides (MF) patches are characterized by a regulatory-like cytokine profile leading to local immune suppression. The proliferation of nevomelanocytes is regulated by cellular senescence mechanisms mediated by immune system. The immunosuppressive effect of MF infiltrate in conjunction with the systemic effect of treatments may play a specific role in the nevomelanogenesis of the patients herein described.

A Novel Nonantibiotic Nitroglycerin-Based Catheter Lock Solution for Prevention of Intraluminal Central Venous Catheter Infections in Cancer Patients.

For long-term central lines (CL), the lumen is the major source of central line-associated bloodstream infections (CLABSI). The current standard of care for maintaining catheter patency includes flushing the CL with saline or heparin. Neither agent has any antimicrobial activity. Furthermore, heparin may enhance staphylococcal biofilm formation. We evaluated the safety and efficacy of a novel nonantibiotic catheter lock solution for the prevention of CLABSI. Between November 2015 and February 2016, we enrolled 60 patients with hematologic malignancies who had peripherally inserted central catheters (PICC) to receive the study lock solution. The study lock consisted of 15 or 30 µg/ml of nitroglycerin in combination with 4% sodium citrate and 22% ethanol. Each lumen was locked for at least 2 h once daily prior to being flushed. After enrollment of 10 patients at the lower nitroglycerin dose without evidence of toxicity, the dose was escalated to the higher dose (30 µg/ml). There were no serious related adverse events or episodes of hypotension with lock administration. Two patients experienced mild transient adverse events (one headache and one rash) possibly related to the lock and that resolved without residual effect. The CLABSI rate was 0 on lock days versus 1.6/1,000 catheter days (CD) off lock prophylaxis, compared with a rate of 1.9/1,000 CD at the institution in the same patient population. In conclusion, the nitroglycerin-based lock prophylaxis is safe and well tolerated. It may prevent CLABSI when given daily to cancer patients. Large, prospective, randomized clinical trials are needed to validate these findings. (This study has been registered at ClinicalTrials.gov under identifier NCT02577718.).

Atypical Spitzoid Neoplasms in Childhood: A Molecular and Outcome Study.

The natural history of atypical Spitz neoplasms remains poorly understood, resulting in significant patient and clinician anxiety. We sought to better characterize outcomes that correlated with molecular features by performing a prospective cohort study of pediatric atypical spitzoid neoplasms in which fluorescence in situ hybridization studies were obtained for diagnosis. Cases with sufficient tissue underwent additional retrospective assessment for translocations in ALK, NTRK1, BRAF, RET, and ROS1. Among 246 total patients assessed, 13% had a positive fluorescence in situ hybridization result. Follow-up data was available in 85 patients. Two patients had a recurrence of whom 1 had distant metastasis. Both patients had homozygous deletions in 9p21. Homozygous deletions in 9p21 significantly correlated with recurrence of disease (P = 0.027). Fifteen (36%) of 42 cases were found to have a kinase fusion protein. However, the presence of kinase fusions was nonprognostic of recurrence (P > 0.99). This study was limited by the availability and length of follow-up data and the number of adverse outcomes. The majority of atypical spitzoid neoplasms in childhood have indolent behavior. Although the subgroup of patients with homozygous deletions in 9p21 is at higher risk for aggressive clinical behavior, their prognosis seems considerably better than similarly staged conventional melanoma.

Eccrine Syringofibroadenoma in Association With Acquired Epidermodysplasia Verruciformis.

A 75-year-old man with human immunodeficiency virus infection and numerous biopsy-proven warts for 10 years, refractory to cryosurgery, cimetidine, and topical imiquimod, presented with numerous pink to hypopigmented verrucous papules and plaques involving the face, trunk, buttocks, and groin. Laboratory evaluation revealed a CD4 T-cell count of 62 cells per microliter and human immunodeficiency virus viral load of <117 copies per milliliter. Biopsy of a plaque groin lesion was performed. Histopathology revealed vertically oriented anastomosing strands of basaloid epithelium arising from multiple points along the epidermis in a background fibrovascular stroma. Ductal differentiation was identified. Areas of epidermis showed compact orthokeratosis, coarse hypergranulosis, and keratinocytes with abundant steel-blue-gray cytoplasm, indicative of viral cytopathic changes. Cytologic atypia was not identified. Human papillomavirus (HPV) genotyping of this lesion was positive for types 5 and 14. Overall, the findings were consistent with epidermodysplasia verruciformis in association with eccrine syringofibroadenoma (ESFA). The patient was subsequently treated with acitretin and showed clinical improvement. ESFA is an uncommon benign adnexal tumor with unknown pathogenesis. Although its association with HPV has rarely been reported, ESFA in the setting of acquired epidermodysplasia verruciformis has not been described. The development of ESFA in this case may be the result of HPV-induced cellular transformation.

Varied Presentations of Pediatric Lipoblastoma: Case Series and Review of the Literature.

Lipoblastoma is a rare neoplasm of embryonal adipose tissue most often encountered on the trunk and extremities of children. It commonly presents as a painless subcutaneous soft tissue mass, but there are other unique clinical presentations that are important to recognize. The differential is broad and includes sarcoma, vascular tumor, myofibroma, and other fibromatoses. We present three varied, distinct cases of pediatric lipoblastoma and review the literature on this condition.

Effect of Lorazepam With Haloperidol vs Haloperidol Alone on Agitated Delirium in Patients With Advanced Cancer Receiving Palliative Care: A Randomized Clinical Trial.

Importance: The use of benzodiazepines to control agitation in delirium in the last days of life is controversial. Objective: To compare the effect of lorazepam vs placebo as an adjuvant to haloperidol for persistent agitation in patients with delirium in the setting of advanced cancer. Design, Setting, and Participants: Single-center, double-blind, parallel-group, randomized clinical trial conducted at an acute palliative care unit at MD Anderson Cancer Center, Texas, enrolling 93 patients with advanced cancer and agitated delirium despite scheduled haloperidol from February 11, 2014, to June 30, 2016, with data collection completed in October 2016. Interventions: Lorazepam (3 mg) intravenously (n = 47) or placebo (n = 43) in addition to haloperidol (2 mg) intravenously upon the onset of an agitation episode. Main Outcomes and Measures: The primary outcome was change in Richmond Agitation-Sedation Scale (RASS) score (range, -5 [unarousable] to 4 [very agitated or combative]) from baseline to 8 hours after treatment administration. Secondary end points were rescue neuroleptic use, delirium recall, comfort (perceived by caregivers and nurses), communication capacity, delirium severity, adverse effects, discharge outcomes, and overall survival. Results: Among 90 randomized patients (mean age, 62 years; women, 42 [47%]), 58 (64%) received the study medication and 52 (90%) completed the trial. Lorazepam + haloperidol resulted in a significantly greater reduction of RASS score at 8 hours (-4.1 points) than placebo + haloperidol (-2.3 points) (mean difference, -1.9 points [95% CI, -2.8 to -0.9]; P < .001). The lorazepam + haloperidol group required less median rescue neuroleptics (2.0 mg) than the placebo + haloperidol group (4.0 mg) (median difference, -1.0 mg [95% CI, -2.0 to 0]; P = .009) and was perceived to be more comfortable by both blinded caregivers and nurses (caregivers: 84% for the lorazepam + haloperidol group vs 37% for the placebo + haloperidol group; mean difference, 47% [95% CI, 14% to 73%], P = .007; nurses: 77% for the lorazepam + haloperidol group vs 30% for the placebo + haloperidol group; mean difference, 47% [95% CI, 17% to 71%], P = .005). No significant between-group differences were found in delirium-related distress and survival. The most common adverse effect was hypokinesia (3 patients in the lorazepam + haloperidol group [19%] and 4 patients in the placebo + haloperidol group [27%]). Conclusions and Relevance: In this preliminary trial of hospitalized patients with agitated delirium in the setting of advanced cancer, the addition of lorazepam to haloperidol compared with haloperidol alone resulted in a significantly greater reduction in agitation at 8 hours. Further research is needed to assess generalizability and adverse effects. Trial Registration: clinicaltrials.gov Identifier: NCT01949662.

Evaluation of dermoscopic features for distinguishing melanoma from special site nevi of the breast.

BACKGROUND: Nevi of special sites display aberrant clinical and histologic features that can be difficult to distinguish from melanoma, leading to unnecessarily high rates of excision with poor cosmetic or functional results. Dermoscopy can improve clinical assessment of melanocytic lesions by visualizing morphologic structures beyond the epidermis. OBJECTIVE: We sought to assess the value of specific dermoscopic features for diagnosing melanocytic neoplasms arising on the breast area in females. METHODS: In this retrospective cohort study, we collected clinical and dermoscopic information for 104 nevi and 13 melanomas removed from the breast, chest, and areola, and evaluated the diagnostic performance of each dermoscopic feature. RESULTS: Melanomas from the breast area were larger (P = .0175) than nevi and occurred in older women (P = .0117). Irregular blotches, nonuniform radial streaks, blue-gray veil, and regression were highly specific for melanoma, whereas atypical network and irregular dots and globules had low to moderate specificity. LIMITATIONS: This study was retrospective with a small sample size. CONCLUSION: Compared to melanocytic neoplasms from other sites, atypical network and irregular dots and globules were poor indicators for breast melanoma. Irregular blotches, nonuniform radial streaks, blue-gray veil, and regression were highly specific and should heighten clinical suspicion for melanoma arising on the breast.

A comparative study of proliferative activity and tumor stage of pregnancy-associated melanoma (PAM) and non-PAM in gestational age women.

BACKGROUND: The influence of pregnancy on the development, progression, and prognosis of melanoma is controversial. OBJECTIVE: We sought to compare clinical characteristics, histologic features, and proliferative activity in pregnancy-associated melanoma (PAM) and melanoma in nonpregnant women of reproductive age (non-PAM). METHODS: In this retrospective cohort study, we reviewed medical records and pathology reports from women given a diagnosis of melanoma between 2006 and 2015. We also examined tumor proliferation rates using mitotic count and 2 immunohistochemical markers of proliferation, phosphohistone H3 and Ki-67. RESULTS: In 50 PAM and 122 non-PAM cases, a diagnosis of melanoma in situ was associated with PAM. Among invasive melanomas, there was no difference in proliferative activity between groups. Pregnancy status was also not associated with age at diagnosis, tumor site, Breslow depth, Clark level, ulceration, or overall stage. LIMITATIONS: This was a retrospective study with a small sample size of mostly patients with early-stage melanoma. CONCLUSIONS: In our study of primarily early-stage melanoma, pregnancy did not have a significant impact on tumor proliferation. Particularly for patients given a diagnosis of stage I melanoma who are undergoing close surveillance, a history of PAM should not outweigh traditional factors, such as advanced maternal age, in planning future pregnancies.

The utility of dermoscopy-guided histologic sectioning for the diagnosis of melanocytic lesions: A case-control study.

BACKGROUND: Dermoscopy allows for visualization of morphologic structures beyond the epidermis, including features that may indicate early malignant transformation. However, dermoscopic features are rarely considered during routine histologic sectioning, and areas of clinical concern may be missed during microscopic evaluation. OBJECTIVE: We assessed the diagnostic impact of a dermoscopy-guided micropunch score for the evaluation of melanocytic lesions. METHODS: In this case-control study, we evaluated 150 scored melanocytic lesions. Original tissue specimens were reprocessed to create a control group, in which a new score was introduced elsewhere in the lesion to guide an alternative plane of section. Slides were reviewed in a randomized, double-blinded manner to assess histologic features and render a diagnosis. Dermoscopy was also reviewed. RESULTS: The proportion of cases with a higher grade in the original, dermoscopy-guided section was statistically significant. Four invasive melanomas were exclusively identified using the scoring protocol. The presence of regression structures, negative pigment network, radial streaming or pseudopods, and irregular blotches were highly specific for a higher diagnostic grade. LIMITATIONS: This study is retrospective and reprocessing tissue does not perfectly mimic routine sectioning. CONCLUSION: Dermoscopy can identify important, histologically high-grade areas, and this information can be used to optimize the sectioning of melanocytic neoplasms.

CD8+ mycosis fungoides clinically masquerading as alopecia areata.

A 33-year-old female with a 7-year history of CD8-positive hypopigmented mycosis fungoides (MF) involving the trunk and extremities presented with a large well-defined alopecic patch on her frontal scalp. Clinically, this area resembled alopecia areata (AA) and was without hypopigmentation or erythema. A scalp biopsy revealed a non-scarring inflammatory alopecia and a superficial band-like atypical lymphoid infiltrate with prominent epidermotropism. Atypical, predominately CD8-positive lymphocytes were seen surrounding and infiltrating the bulb portion of several hair follicles. Treatments for her MF lesions have included topical bexarotene, topical corticosteroids and phototherapy. Her alopecia has been treated with high potency topical corticosteroids and multiple intralesional triamcinolone injections with very minimal hair regrowth to date. Alopecia due to cutaneous lymphoma is an uncommon phenomenon but can occur in erythrodermic MF or Sezary syndrome. AA-like changes have most often been reported in conventional patch/plaque stage MF and folliculotropic MF. In these cases, the atypical lymphoid infiltrate is comprised predominately of CD4-positive lymphocytes. This is a rare report of a CD8-positive MF causing AA-like changes. This case highlights the importance of a scalp biopsy in patients with a history of cutaneous lymphoma presenting with alopecia in order to evaluate the nature of their hair loss.

Primary Cutaneous Mammary Analog Secretory Carcinoma With ETV6-NTRK3 Translocation.

Mammary analog secretory carcinoma (MASC) is a recently described tumor of the salivary glands named for its morphological and molecular similarity to secretory carcinoma of the breast. Many primary carcinomas arising from the adnexal glands also share similar morphology to those arising from the breast. Brandt et al first described primary cutaneous MASC in 2009 and since then only 2 other cases have been reported. Herein, we describe a long-standing mass on the arm of an otherwise healthy 40-year-old female. Histologic examination revealed a circumscribed but unencapsulated, nodular tumor composed of bland epithelial cells arranged in solid and microcystic growth patterns. The cells showed vacuolated cytoplasm and round to oval nuclei with vesicular chromatin. Intraluminal homogenous eosinophilic secretions were present. Mitotic figures were not identified. The tumor cells stained positive for CK8/18, CK7, and S100 but were negative for other markers performed, including estrogen receptor, progesterone receptor, HER2/neu, paired box 8 (PAX8), and thyroid transcription factor 1 (TTF1). As the patient clinically had no other masses or known carcinomas, a diagnosis of primary cutaneous MASC was rendered. The ETV6-NTRK3 fusion transcript was subsequently detected by reverse transcriptase polymerase chain reaction amplification, further supporting the diagnosis. We present this case to review the histologic features of MASC and highlight the importance of recognizing this lesion not only as a possible cutaneous metastasis but also as a primary cutaneous tumor.

Combined cutaneous tumors with a melanoma component: A clinical, histologic, and molecular study.

BACKGROUND: The histogenesis and clinical behavior of combined cutaneous tumors (CCTs) in which the mesenchymal component consists of melanoma remain unclear. OBJECTIVE: We sought to characterize the clinical, histologic, and molecular findings in CCTs with an epithelial and a melanoma component. METHODS: We retrospectively reviewed the records from 2 institutions for CCTs. Fluorescence in situ hybridization was performed to assess chromosomal copy number alterations in both components. RESULTS: Sixteen CCTs were included. The most common subtype was the squamomelanocytic tumor (11), followed by the basomelanocytic tumor (3) and the trichoblastomelanoma (2). CCTs were more common in men (87%), on the head and neck (57%), and had extensive solar elastosis (81%). The median follow-up was 25 months (range, 8-167 months). One case had an adverse outcome. Fluorescence in situ hybridization revealed chromosomal alterations in approximately 55% of the cases. Five cases showed chromosomal gains only in the melanocytic component. One case showed 11q13 gains in both the epithelial and melanocytic components. LIMITATIONS: Our study is retrospective and the sample is small. CONCLUSIONS: The low incidence of adverse outcomes suggests that CCT may be more indolent than noncombined tumors. 11q13 amplification in both components supports the theory of dual differentiation from a common progenitor cell.

Morphologic clues and utility of fluorescence in situ hybridization for the diagnosis of nevoid melanoma.

BACKGROUND: Nevoid melanomas include melanomas with a low power silhouette similar to melanocytic nevi. However, at higher power magnification, nevoid melanoma may have severe nuclear atypia and dermal mitoses. METHODS: We performed a clinical, pathological and molecular study on a series of 58 examples of nevoid melanoma, excluding cases with spitzoid morphology. RESULTS: We identified distinct morphologic patterns: 'classic' nevoid melanoma, superficial spreading melanomas with nevoid invasive melanoma, lentigo maligna with nevoid invasive melanoma and deep penetrating nevus-like nevoid melanoma. Fluorescence in situ hybridization (FISH) was positive in 74% of cases. Copy number gains in 8q24 were common in amelanotic nevoid melanoma. The median follow-up was 28 months (range 140). At last follow-up, 37 patients had no evidence of disease, 3 were alive with metastases and 6 died from metastatic melanoma. Of these six patients who died, four had a sentinel lymph node biopsy (SLNB) performed, which was negative in all four. CONCLUSIONS: We describe distinct clues to the diagnosis of nevoid melanoma including occult intraepidermal atypia, and expansile nesting resulting in asymmetric silhouette or dermal papillae expansion. We also describe that nevoid melanoma have infrequent SLNB involvement in aggressive cases, and have frequent 8q24 gains rather than 9p21 deletions. Our results suggest that nevoid melanoma are distinct from spitzoid melanomas and should be distinguished.

Large cell acanthoma: a variant of solar lentigo with cellular hypertrophy.

BACKGROUND: Large cell acanthoma (LCA) is an epidermal proliferation of enlarged keratinocytes. There is a lack of consensus on whether it represents a unique neoplasm or not. To determine whether it is a variant of solar lentigo, we compared macroscopic, microscopic and immunophenotypic attributes of LCA with conventional solar lentigo, seborrheic keratosis, actinic keratosis and Bowen disease. METHODS: We constructed tissue microarrays containing multiple cores of LCA, solar lentigo, seborrheic keratosis, actinic keratosis and Bowen disease. Tissue microarray sections were blindly analyzed for microscopic morphologic variables. Corresponding ex vivo dermoscopic images from the original cases were blindly analyzed for macroscopic morphologic variables. Immunostained sections from the tissue microarray were tested for keratin 10, keratin 5/6, Bcl-2 and Ki-67 expression by image analysis. RESULTS: There were no significant differences in the studied morphologic attributes between LCA and solar lentigo. All other tumor classes showed at least one significant morphologic difference with LCA. LCA and solar lentigo showed different keratin 10 and Bcl-2 signal intensities. CONCLUSIONS: LCA is best considered a variant of solar lentigo with cellular hypertrophy. The differences in immunophenotype and cell size could be because of differences in cell kinetics.

Standardization of key performance indicators and metrics for investigational drug services (IDS): Consensus recommendations among IDS specialists.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: There are currently no consensus guidelines on establishing metrics for investigational drug services (IDS). Because of the complexity of research protocols, it remains difficult for sites to track pharmacy productivity and create a baseline for IDS growth within the institution, as well as to perform benchmarking with peer institutions. The goal of this study was to help establish practical guidance for IDS metrics and site utility as applicable. METHODS: This was a survey-based project conducted by the metrics subgroup of the Hematology/Oncology Pharmacy Association (HOPA) IDS special interest group (SIG), which was formed specifically for this analysis. Three surveys developed by the metrics subgroup were sent to members of the IDS HOPA SIG to gather metrics. The first survey included questions about what metrics IDS sites currently collect. The identified metrics were then condensed into categories. Through a consensus-based approach, standardized definitions were established and applied to future surveys. The 2 subsequent surveys sent to HOPA SIG members helped create a list of top recommended metrics that are recommended for every IDS site to track. RESULTS: A total of 3 surveys were sent to 75 recipients, with the response rate ranging from 24% to 38%. From these surveys and consensus with the metrics subgroup, 5 top recommended metrics were identified: (1) active protocols; (2) dispenses; (3) new clinical trials initiated; (4) patients treated; and (5) clinical interventions. CONCLUSION: These recommended metrics should serve as guidance and allow for standardization to help ensure adequate resources are available for IDS pharmacy staff. These recommendations should serve as a basis for standardization and benchmarking with peer institutions.

Progressive nodular histiocytosis with normal karyotypic analysis.

Non-Langerhans cell histiocytoses (NLH) comprise a spectrum of diseases that includes sinus histiocytosis with massive lymphadenopathy, hemophagocytic lymphohistiocytosis, xanthogranuloma, and reticulohistiocytoma. Progressive nodular histiocytosis (PNH) is a rare NLH that microscopically mimics juvenile xanthogranuloma but presents with disseminated persistent and progressive papulonodules in adults. Herein, we describe a case of PNH presenting as diffuse, progressively enlarging papules, nodules, and pedunculated tumors in a 38-year-old male. The diagnosis is supported microscopically by the morphologic and immunohistochemical findings. Whereas conventional cytogenetic analysis of Langerhans cell histiocytosis and juvenile xanthogranuloma has previously been described, there are no reports of the karyotype of PNH. In our patient, conventional cytogenetic analysis of the tumor revealed a normal karyotype. Although these results may represent the overgrowth of normal stromal cells rather than lesional cells, we believe this to be an important finding, indicating karyotypic analysis will not allow for distinction between PCH and other NLH or Langerhans cell histiocytoses.