Typically, a solitary KA grows larger than 2cm. It particularly occurs in males chronically exposed to the sun and is more frequent in smokers. Frequently, the definition of PTLD is limited to lymphomatous lesions (localized or diffuse) that are often extranodal (often in the allograft). The infectious causes of lymphadenopathy are listed in Table 1 because they are occasionally mistaken for malignancy (e.g. Keratoacanthoma arises from the infundibulum of the hair follicle. The histological diagnosis of Castleman's disease is not trivial and the accuracy of the diagnosis has not been tested. Accessed Oct. 1, 2020. Other treatments have included retinoic acid,57 humanized anti-IL-6 receptor antibodies,51 anti-IL-6 antibodies and bone marrow transplantation.58, 59. Preliminary results of a phase II trial of low-dose cyclophosphamide in posttransplant lymphoproliferative disorders and the use of GM-CSF as preemptive therapy are presented. Polyclonal, oligoclonal or monoclonal proliferations may be observed, even within different lesions in the same patient. Neoplasms of the immune system in rheumatoid arthritis. Vascularity is increased in the interfollicular regions.43,44,45 The plasma cell variant is largely composed of extensive proliferations of plasma cells in the interfollicular regions with follicles maintained. Because no clinical or pathologic features can reliably differentiate keratoacanthoma from squamous cell carcinoma, early simple excision of lesions is recommended, with margins of 3 to 5 mm. Mutational Analysis of BRAF Inhibitor-Associated Squamoproliferative Lesions. Chadburn A, Cesarman E, Liu YF, et al. After several weeks of stability, the lesion starts to spontaneously regress, eventually leaving a depressed scar. They tend to occur on the head or neck, or at sites of previous penetrating trauma. Many factors can make normal cells appear atypical, including inflammation and infection. Infected cysts tend to be larger, more erythematous, and more painful than sterile inflamed cysts. ATYICAL NEVUS - mole showing atypical cell growth rated on a scale of mild, moderate, or severe by how much atypical cell growth is seen under the microscope by the pathologist a. Treatment of post-transplant lymphoproliferative disease (PTLD) following solid organ transplantation with low dose chemotherapy. Sneller MC, Wang J, Dale JK, et al. Immunophenotyping the tissue biopsy appears to provide no assistance in distinguishing lupus-associated lymphadenopathy from the similar appearing Kikuchi's disease.18 Kikuchi's disease is a type of necrotizing lymphadenitis with proliferation of histiocytes and immunoblasts that occurs most frequently in young women of east Asian descent. Frequent T and B cell oligoclones in histologically and immunophenotypically characterized angioimmunoblastic lymphadenopathy. Using IFN, 40-50% of patient may achieve a complete remission (CR).66 DLI has been demonstrated to be successful in the treatment of PTLD post-BMT.74 However, severe GVHD has also been associated with DLI, and deaths due to a shock-like syndrome have been reported.75,120 DLI is not always successful at controlling PTLD. The role of antiviral prophylaxis with acyclovir or ganciclovir is controversial, since most patients are receiving antiviral therapy when PTLD develops.61, 65, 66, 69, 78 Since EBV cannot be cultured, polymerase chain reaction (PCR) of the blood is used to detect infection or reactivation, and semiquantitative determination of EBV DNA in peripheral blood, i.e. In: Epstein MA, Achong BG, eds. EBV-LPD is a growing problem due to increasing numbers of transplant recipients. It is usually best to assume a KA-like lesion is an SCC and to manage accordingly in line with local or national guidance, until proven otherwise. Intensity-modulated radiation therapy (IMRT), Mouth sores caused by cancer treatment: How to cope, No appetite? official website and that any information you provide is encrypted Two varieties of changing and atypical lesions are seen: squamoproliferative and melanocytic. It has a lower malignancy potential than conventional squamous cell carcinomas. What is a gum biopsy? Lucas KG, Small TN, Heller G, Dupont B, O'Reilly RJ: The development of cellular immunity to Epstein-Barr virus after allogeneic bone marrow transplantation. About 50,000 new cases of non-melanoma skin cancer are estimated to occur in New Zealand each year by far the most common of all cancers. In the XLP Registry, 38 males (12.5%) have had no evidence of EBV infection at the time of first clinical manifestation. Problems in the current TNM staging of nonmelanoma skin cancer of the head and neck. Angioimmunoblastic lymphoma (AILD-type T cell lymphoma) with hyperplastic germinal centers. However, this treatment should probably be offered to patients with progressive but otherwise unresponsive disease. Correlation of mutations of the SH2D1A gene and Epstein-Barr virus (EBV) infection with clinical phenotype and outcome in X-linked lymphoproliferative disease (XLP). Gams RA, Neal JA, Conrad FG. The etiology of the lymphadenopathy in most patients with ALPS is related to an impairment of apoptosis due to inherited heterozygous mutations in the fas gene (tumor necrosis factor receptor gene superfamily member 6-TNFRSF6, CD95, APO-1, APT-1), which is referred to as ALPS type I.19, 22, 23 Rare cases have been described of ALPS type II (mutations in caspase 10) and type III, wherein no mutation has been identified, however a functional deficiency of fas-mediated apoptosis has been observed.24, 25 Rare patients have developed T cell rich B cell large cell lymphoma and nodular lymphocyte predominant Hodgkin's disease. In a young patient who has persisting, symptomatic Castleman's disease, autologous bone marrow transplantation might be considered. The use of dermoscopy to improve diagnosis has been addressed in a previous article in American Family Physician.4 However, the preferred method of diagnosing skin cancer is physical examination. Atypical cells don't necessarily mean you have cancer. For patients who fail to resolve the PTLD or develop rejection after reduction of immune suppression, cytotoxic chemotherapy is attractive since it will treat both processes.81 However, standard dose chemotherapy for treating NHL may be toxic for post-transplant patients and may theoretically inhibit EBV-CTL development.85,98 Therefore, we have been conducting a multicenter study using low-dose chemotherapy. The approach to treating EBV-LPD is likely to reflect one's theory about the underlying etiology of the disease. other information we have about you. Third, the use of closely matched relatives' leukocytes runs the risk of both rejection and GVHD. Bowne WB, Lewis JJ, Filippa DA, et al. Epstein-Barr virus-associated hemophagocytic syndrome and fatal infectious mononucleosis. Swinnen LJ, Mullen GM, Carr TJ, et al. After several weeks of stability, the lesion starts to spontaneously regress, eventually leaving a depressed, Diagnosis may be difficult and they may be confused with. Unauthorized use of these marks is strictly prohibited. 8600 Rockville Pike In that disease, a proliferation of large histiocytes contain phagocytosed lymphocytes (emperiolopoiesis), resulting in lymphadenopathy in the neck (also known as sinus histiocytosis with massive lymphadenopathy). Click here for an email preview. Seemayer TA, Gross TG, Hinrichs SH, Egeler RM. Seventy-nine percent had splenomegaly and 63% hepatomegally. Invasive SCC is nearly always treated surgically. First report of Epstein-Barr virus lymphoproliferative disease after cord blood transplantation. Alizadeh AA, Eisen MB, Davis RE, et al. Keratoacanthomas are sharply demarcated, firm, erythematous or skin-coloured, with a classic central hyperkeratotic plug and an even shoulder. graft rejection) or do not respond to immunosuppression reduction require more aggressive therapy and have a much poorer prognosis.65,85 Antiviral agents (acyclovir or ganciclovir) and/ or IVIG have been used extensively for prophylaxis and treatment of PTLD.61,62,65,85 The efficacy of antivirals and IVIG is difficult to assess because reduction of immune suppression is almost always initiated simultaneously. FOIA They may grow to 1 to 2 cm over weeks or months. The most common locations are in skin folds (e.g., neck, axillae, groin), where skin irritation can be a causative factor. Authors: Associate Professor Amanda Oakley, 1999; updated by Katrina Tan, Medical Student, Monash University, Melbourne, Australia; Dr Martin Keefe, Dermatologist, Christchurch, New Zealand. Copy edited by Gus Mitchell. They may be treated with electrodesiccation, laser ablation, curettage, cryosurgery, or shave excision if biopsy is required. Night sweats, weight loss, and antibody-mediated anemia may occur.27, 28 The Coombs' test is frequently positive and occasionally a small monoclonal protein may be identified. Keratoacanthomas are rapidly growing, squamoproliferative benign tumors that resemble squamous cell carcinomas. HHS Vulnerability Disclosure, Help With the ongoing success of these drugs in clinical trials, these lesions are likely to be more often encountered in routine dermatopathology practice. A gum biopsy is a medical procedure in which a doctor removes a sample of tissue from your gums. 2013;40(6):44352. Though benign, they are worth more of your attention because individuals with atypical moles are at increased risk for melanoma, a dangerous skin cancer. Clinically, it presents as a scaly white atrophic patch or plaque on the glans or foreskin that may become significantly sclerosed causing phimosis and stricturing of the urethral meatus. Kuehnle I, Huls MH, Liu Z, et al. Non-scaly actinic keratosis Clinical characteristics of post-transplant lymphoproliferative disorders. Aust Fam Physician. Kwiek B, Schwartz RA. In 32 patients, treated for lymphoid malignancies and ataxia-telangiectasia (AT), the complete remission (CR) rate was 50% and median survival overall was about 6 months, and 32 months for those who achieved CR. Eosinophilic material or hyalinization is present in variable amounts around the vessels. Milpied N, Vasseur B, Parquet N, et al. Benign Squamoproliferative Lesions That Mimic SCC 2.1. Nalesnik MA, Makowka L, Starzl TE. These atypical lymphoproliferations can be aggressive with continued immunosuppression, even when polyclonal or oligoclonal, as defined by immunoperoxidase and gene rearrangement studies. Another biopsy to confirm the diagnosis might be appropriate. Cutaneous toxicities of BRAF inhibitors: clinical and pathological challenges and call to action. Distinguishing between KA and SCC using haematoxylin and eosin-stained sections from an initial biopsy can often be difficult. Squamous cell carcinoma of the skin (non-metastatic), Describe the clinical features and management of, 4 to 16 weeks of imiquimod cream applied two or three times weekly. The role of 2-chlorodeoxyadenosine in the treatment of patients with refractory angioimmunoblastic lymphadenopathy with dysproteinemia. sharing sensitive information, make sure youre on a federal In addition to the type of organ received, additional risk factors for PTLD in the SOT include the frequency of rejection episodes requiring intensified immunosuppression, especially the use of T cell antibody therapy, EBV seronegative status at time of transplant, and younger age of recipients, especially less than 5 years of age at time of transplant.65,85,112, 113 Over 90% of early (fewer than 6 months post transplantation) PTLDs are EBV positive, whereas late (more than 2 years) PTLDs tend to be EBV negative. In primary immunodeficient patients and many BMT patients, the patient does not have enough T cell immunity for this approach to be effective.64,65,66 Infusion of donor lymphocyte (DLI) has been successful in BMT patients,74 but the donor must be EBV seropositive and possess memory EBV-CTL.76 To reduce the risk of GVHD and enhance efficacy, EBV-specific CTL generated ex vivo have been used successfully in preventing and treating EBV-LPD.76 Again, ex vivo generation of EBV-CTL is generally performed with EBV-seropositive donors to expand memory CTL. Polymorphic diffuse B cell hyperplasias and lymphomas in renal transplant recipients. MeSH 108 Though the majority of the lesions are EBV positive, occasionally B cell or Hodgkin's disease will be EBV negative, especially if occurring late (more than 1 year post transplant). The site is secure. The purpose of this review is to describe the pathology of selected entities and provide focused discussions on the therapy of Castleman's disease and Epstein-Barr virus (EBV)-related lymphoproliferations in immunodeficiency conditions. The risk factors are probably the same as for squamous cell carcinoma, and include: Keratoacanthomas typically present as a solitary, rapidly growing nodule on sun-exposed skin of the face and upper limbs. In XLP, about 70% of boys achieved a CR with chemotherapy, but more than half relapsed. The median time post-transplant when GM-CSF was started was 52 days (48-70 days). Metastatic disease is uncommon. Association with previous medications such as antibiotics and anticonvulsants and viral infections has been reported. Dotti G, Fiocchi, Motts T, et al. This is the American ICD-10-CM version of D48.5 - other international versions of ICD-10 D48.5 may differ. This is a corrected version of the article that appeared in print. window.__mirage2 = {petok:"npqJSG.kMH6aHZ7nUAWJEmfS1KPOnIlRcLI8bsTxGzU-1800-0"}; Actinic keratoses are predominantly treated by cryotherapy. Squamous cell carcinoma Both TCR and immunoglobulin gene rearrangements are found in about 10% of cases.35, 36 Occasionally there have been cases of B cell lymphomas described in a previous background of AILD. Seborrheic keratoses and cherry angiomas generally do not require treatment. IFN- can be marrow suppressive, increasing the risk of secondary infection, and theoretically may increase the risk of organ rejection or GVHD. Dermatofibromas result from idiopathic benign proliferation of fibroblasts. The cause is unknown; however, the course is usually limited. 2013 Nov;88(2):318-37. doi: 10.1016/j.critrevonc.2013.06.002. Humanized anti-CD20 monoclonal antibody (Rituximab) in post transplant B-lymphoproliferative disorder: a retrospective analysis on 32 patients. Squamous cell carcinoma A recent study demonstrated only 2/7 patients with PTLD to be alive without disease following DLI; four patients died of progressive disease and one died of GVHD following CR.75 Ex vivo EBV-specific CTL has been shown to be effective as prophylactic, pre-emptive therapy and treatment for PTLD post-BMT.76 But as stated previously, this technology is not readily available in most centers. Many of these uncommon lymphoproliferations are related to an abnormal immune response to some inciting stimulus. IVIG, antivirals and/or IFN adds little toxicity. There is a problem with Immunologic Disorders of Infants and Children. Schiavoni G, Mattel F, Di Pucchio T, et al. Please enable it to take advantage of the complete set of features! To our knowledge this represents the first detailed histological analysis of the squamoproliferative lesions which arise in the context of treatment with BRAF inhibitors, and highlights the morphological diversity of these lesions. information submitted for this request. We undertook a histopathological review of lesions excised from patients on BRAF inhibitor therapy, and found that 73% of lesions were squamoproliferative in nature. Mild - very common and generally less potential of becoming more aggressive a.i. Wide margins are advisable for poorly differentiated or anaplastic tumours. If you have any concerns with your skin or its treatment, see a dermatologist for advice. Smir BN, Greiner TC, Weisenburger DD. Bardwick PA, Bluestein HG, Zvaifler NJ, et al. Their prevalence is 1%.9, Lipomas must be clinically differentiated from other tumors. Reversible monoclonal lymphadenopathy in autoimmune lymphoproliferative syndrome with functional FAS (CD95/APO-1) deficiency. IFN- has been used successfully to treat EBV-LPD in both primary and post-transplant patients.65,66,67,68,69 IFN- may have antiviral, anti-B cell proliferative, and/or T cell-enhancing effects. Am Fam Physician. Cohen DN, Lawson SK, Shaver AC, Du L, Nguyen HP, He Q, Johnson DB, Lumbang WA, Moody BR, Prescott JL, Chandra PK, Boyd AS, Zwerner JP, Robbins JB, Tyring SK, Rady PL, Chappell JD, Shyr Y, Infante JR, Sosman JA. Squamous cell carcinoma CME. Bethesda, MD 20894, Web Policies Peterson BA, Frizzera G. Multicentric Castleman's disease. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. Florid follicular hyperplasia is frequently present; however, in some cases follicular involution as seen in Castleman's disease has been reported. Data from the Immunodeficiency Cancer Registry for lymphoproliferations are shown in Table 2. Repetto L, Jaiprakash MP, Selby PJ, Gusterson BA, Williams HJ, McElwain TJ. Atypical lymphoplasmacytic and immunoblastic proliferation in lymph nodes of patients with autoimmune disease (autoimmune-disease-associated lymphadenopathy). Avila NA, Dwyer AJ, Dale JK, et al. They often arise within a benign adnexal lesion. In recent years, there has been increasing use of several novel agents that specifically target the V600E BRAF mutation in melanoma and other malignancies. Ultrasonography can aid in the diagnosis of lipomas. With the current rate of transplantation, it is estimated that there are 500-1500 new cases of PTLD a year in the US. Keratoacanthoma (KA) is a cutaneous squamoproliferative tumor that usually presents as a 1 to 2 cm dome-shaped or crateriform nodule with central hyperkeratosis ( picture 1A-E ). Savage JA, Maize JC, Sr. Keratoacanthoma clinical behavior: a systematic review. The lack of an appropriate T cell response commonly results in an EBV-driven B cell proliferation, but a polyclonal, non-specific proliferation of B cells and T cells may occur as seen typically in FIM.2, 4, 60 If unchecked, this extensive infiltration of lymphoid and parenchymal organs by polyclonal T and B cells as well the often observed histiocytic reaction with hemophagocytosis can be fatal. The approach most widely used as initial therapy of PTLD is reduction of immunosuppression. There is no unifying system for classifying atypical lymphoproliferations (ALP) that predicts whether a patient will have a self limited illness or one that will eventually result in lymphoma or death. Would you like email updates of new search results? Prevention and preemptive therapy of posttransplant lymphoproliferative disease in pediatric liver recipients. Exp Dermatol. Atypical cells can change back to normal cells if the underlying cause is removed or resolved. Failure in immunological control of the virus infection: fatal infectious mononucleosis. Cutaneous horn The https:// ensures that you are connecting to the Khanna R, Bell S Sherritt M, et al. They are usually subcutaneous but may occur in any organ because they are mesenchymal. JAMES C. HIGGINS, CAPT, MC, USN, RET, MICHAEL H. MAHER, CAPT, MC, USN, RET, AND MARK S. DOUGLAS, LCDR, MC, USN. Since FIM is essentially indistinguishable from other hemophagocytosis syndromes, it is now recommended that patients receive chemotherapy with etoposide (VP-16) with steroids and/or cyclosporine.60 Approximately 75% will have a complete response, but relapse is common. Swerdlow SH. doi: https://doi.org/10.1182/asheducation.V2000.1.133.133. Sebaceous hyperplasia presents as asymptomatic, discrete, soft, pale yellow, shiny bumps on the forehead or cheeks, or near hair follicles. Filipovich AH, Jyonouchi H, Gross TG, Shapiro RS. Clonal T cell gene rearrangements are present in many cases, supporting the concept that AILD is a peripheral T cell lymphoma in most cases. High-frequency ultrasonography (greater than 20 MHz) can provide high-resolution images of subcutaneous tumors and surrounding structures.10 The differential diagnosis of lipomas also includes liposarcomas; risk factors for malignancy are size greater than 10 cm, older age, rapid lesion growth, location on the thigh, and invasion into deeper tissue, such as nerve or bone, leading to a firm or fixed feeling on examination. Combination chemotherapy with regimens such as cyclophosphamide, vincristine, and prednisone (CVP) has been utilized, but is associated with considerable risk for serious infection. Foss HD, Araujo I, Demel G, et al. And sometimes, your doctor may need to obtain a sample of tissue such as a biopsy to make sure you don't have cancer or another serious condition. Solitary actinic keratosis Dermatofibromas are an idiopathic benign proliferation of fibroblasts. This content does not have an English version. Infusions of donor leukocytes to treat Epstein-Barr virus-associated lymphoproliferative disorders after allogeneic bone marrow transplantation. However, in the majority of cases, the only way to develop appropriate T cell immunity against EBV and cure is to correct the underlying immune defect by allogeneic stem cell transplant, if a suitable donor can be identified.60,64,92, 93 In the case of FIM, many treatments have been utilized, including antibiotics, steroids, IVIG, acyclovir, interferon (both and ), chemotherapy and/or cyclosporin. Am J Dermatopathol. Reaction to imiquimod The diagnosis and treatment of posttransplant lymphoproliferative disorders. Other causes of these findings such as human immunodeficiency virus, other infections, or autoimmune disease must be ruled out prior to the diagnosis of Castleman's disease.43,44,45 Studies of clonality in Castleman's disease have shown that most patients have a polyclonal lymphoproliferative process.46 The development of monoclonality might represent transformation to a malignant lymphoma as immunohistochemical and gene rearrangement studies have identified clonal cell populations in some cases of multicentric Castleman's disease.47, 48. Brandt SJ, Bodine DM, Dunbar CE, Nienhuis AW. The histological characteristics of keratinocytic tumours are illustrated below. They are generally asymptomatic but may become irritated with trauma or produce local obstructive symptoms in the airway or gastrointestinal tract. The complications of keratoacanthoma include: Keratoacanthoma is diagnosed on the basis of a typical history, the clinical signs and histopathology. Misago N, Inoue T, Koba S, Narisawa Y. Keratoacanthoma and other types of squamous cell carcinoma with crateriform architecture: classification and identification. Symmons DPM. Topics AZ In Section III, Dr. Patients with peripheral, localized masses can be treated with excision.55 Patients in whom the disease is localized but not amenable to surgery can be successfully treated with radiotherapy.56 Patients with disseminated disease can sometimes be successfully treated with corticosteroids. The use of cDNA microarray technology offers us a powerful tool for advancing our understanding of the pathogenesis of EBV-LPD as well as providing better prognostication for response to therapy.121 Collaborative multicenter randomized trials are desperately needed to advance our therapeutic options and improve outcome in this patient population. A practical approach to patients with Castleman's disease involves confirmation of the histological diagnosis and a careful staging evaluation. Remission of giant lymph node hyperplasia with anemia after radiotherapy. In other cases, your doctor may recommend a particular treatment to try to reverse the process that's causing the atypical cells. Data Sources: A series of PubMed searches were completed in Clinical Queries using the key terms acrochordon, sebaceous hyperplasia, lipoma, keratoacanthoma, pyogenic granuloma, dermatofibroma, epidermal inclusion cysts, seborrheic keratosis, and cherry angiomas. Mohs micrographic surgery may be considered if tissue sparing is desired.14, Medical treatment (systemic retinoids or intralesional injections of methotrexate, fluorouracil, or bleomycin) is reserved for nonsurgical candidates, patients with multiple lesions, and those with lesions on inoperable sites.15,16, Pyogenic granulomas are rapidly growing nodules that bleed easily. FOIA Actinic keratosis Return to the office for follow up in 3 or 6 months per provider and have area checked doi:10.1111/j.1524-4725.2004.30080.x. Diagnosis of dermatofibromas is based on the characteristic appearance and dimpling or retraction of the lesion beneath the skin with lateral compression. How to get nutrition during cancer treatment, Infographic: Scalp Cooling Therapy for Cancer, Stem cells: What they are and what they do, Thalidomide: Research advances in cancer and other conditions, TVEC (Talimogene laherparepvec) injection, When cancer returns: How to cope with cancer recurrence. Copyright 2023 by American Society of Hematology, Medication-Associated Atypical Lymphoproliferations, Angioimmunoblastic Lymphadenopathy with Dysproteinemia, Treatment of EBV-Associated Lymphoproliferative Disorders in Primary and Secondary Immunodeficiencies, https://doi.org/10.1182/asheducation.V2000.1.133.133, posttransplant lymphoproliferative disorder, Abbreviation: EBV, Epstein-Barr virus associated, Abbreviations: SCID, severe combined immunodeficiency; XLA, X-linked agammaglobulinemia; CVID, common variable immunodeficiency, CHOP +/- Bleo, COMLA, M-BACOD, VACOP-B, Ifos/VP-16/Dex, CY, Adria, VCR, MTX, AraC + IT, ABVD-MOPP, Abbreviations: Promace-CytoBOM, prednisone, vincristine (VCR), doxorubicin (Adria), methotrexate (MTx), cytosine arabinoside (Ara-C), bleomycin (Bleo), cyclophosphamide (Cy), etoposide (Vp 16); CHOP, Cy, Adria, VCR, prednisone; COMLA, Cy, VCR, MTx, Leukcovorin, Ara-C; M-BACOD, Mtx, Bleo, Cy, VCR, dexamethasone (Dex); VACOP-B, Vp6, Adria, Cy, VCR, Bleo; Ifos, ifosfamide; IT, intrathecal; CR, complete remission; DFS, disease-free survival. With the identification of the genetic defects in inherited immunodeficiencies, we should learn much about how the immune system functions and the elements required to prevent and to control EBV and LPD, as well as lymphoproliferations in general. Some patients will achieve a durable remission. : Posttransplant T cell lymphoproliferative disorders-an aggressive, late complication of solid-organ transplantation. Discuss the evidence for the effectiveness of sunscreens in the management of actinic keratoses. Most patients are over 60 years of age and it is twice as common in males than in females. Dermatol Surg. This site needs JavaScript to work properly. arrow-right-small-blue There are several variants and syndromes of keratoacanthoma: Keratoacanthomas are much less common in patients with skin of colour, but the clinical features are the same.
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