Systematic Implementation of Effective Quality Assurance Processes for the Assessment of Radiation Target Volumes in Head and Neck Cancer.

PURPOSE: Significant heterogeneity exists in clinical quality assurance (QA) practices within radiation oncology departments, with most chart rounds lacking prospective peer-reviewed contour evaluation. This has the potential to significantly affect patient outcomes, particularly for head and neck cancers (HNC) given the large variance in target volume delineation. With this understanding, we incorporated a prospective systematic peer contour-review process into our workflow for all patients with HNC. This study aims to assess the effectiveness of implementing prospective peer review into practice for our National Cancer Institute Designated Cancer Center and to report factors associated with contour modifications. METHODS AND MATERIALS: Starting in November 2020, our department adopted a systematic QA process with real-time metrics, in which contours for all patients with HNC treated with radiation therapy were prospectively peer reviewed and graded. Contours were graded with green (unnecessary), yellow (minor), or red (major) colors based on the degree of peer-recommended modifications. Contours from November 2020 through September 2021 were included for analysis. RESULTS: Three hundred sixty contours were included. Contour grades were made up of 89.7% green, 8.9% yellow, and 1.4% red grades. Physicians with >12 months of clinical experience were less likely to have contour changes requested than those with <12 months (8.3% vs 40.9%; P < .001). Contour grades were significantly associated with physician case load, with physicians presenting more than the median number of 50 cases having significantly less modifications requested than those presenting <50 (6.7% vs 13.3%; P = .013). Physicians working with a resident or fellow were less likely to have contour changes requested than those without a trainee (5.2% vs 12.6%; P = .039). Frequency of major modification requests significantly decreased over time after adoption of prospective peer contour review, with no red grades occurring >6 months after adoption. CONCLUSIONS: This study highlights the importance of prospective peer contour-review implementation into systematic clinical QA processes for HNC. Physician experience proved to be the highest predictor of approved contours. A growth curve was demonstrated, with major modifications declining after prospective contour review implementation. Even within a high-volume academic practice with subspecialist attendings, >10% of patients had contour changes made as a direct result of prospective peer review.

Disseminated histoplasmosis presenting as pyoderma gangrenosum-like lesions in a patient with acquired immunodeficiency syndrome.

A 33-year-old Hispanic woman with newly diagnosed human immunodeficiency virus (HIV) infection, a CD4 T-lymphocyte count of 2, viral load of 730,000 copies/mL, candidal esophagitis, seizure disorder, a history of bacterial pneumonia, and recent weight loss was admitted with tonic clonic seizure. On admission, her vital signs were: pulse of 88, respiration rate of 18, temperature of 37.7 degrees C, and blood pressure of 126/76. Her only medication was phenytoin. On examination, the patient was found to have multiple umbilicated papules on her face, as well as painful, erythematous, large, punched-out ulcers on the nose, face, trunk, and extremities of 3 months' duration (Fig. 1). The borders of the ulcers were irregular, raised, boggy, and undermined, while the base contained hemorrhagic exudate partially covered with necrotic eschar. The largest ulcer on the left mandible was 4 cm in diameter. The oral cavity was clear. Because of her subtherapeutic phenytoin level, the medication dose was adjusted, and she was empirically treated with Unasyn for presumptive bacterial infection. Chest radiograph and head computed tomography (CT) scan were within normal limits. Sputum for acid-fast bacilli (AFB) smear was negative. Serologic studies, including Histoplasma antibodies, toxoplasmosis immunoglobulin M (IgM), rapid plasma reagin (RPR), hepatitis C virus (HCV), and hepatitis B virus (HBV) antibodies were all negative. Examination of the cerebrospinal fluid was within normal limits without the presence of cryptococcal antigen. Blood and cerebrospinal cultures for bacteria, mycobacteria, and fungi were all negative. Viral culture from one of the lesions was also negative. The analysis of her complete blood count showed: white blood count, 2300/microl; hemoglobin, 8.5 g/dL; hematocrit, 25.7%; and platelets, 114,000/microl. Two days after admission, the dermatology service was asked to evaluate the patient. Although the umbilicated papules on the patient's face resembled lesions of molluscum contagiosum, other infectious processes considered in the differential diagnosis included histoplasmosis, cryptococcosis, and Penicillium marnefei. In addition, the morphology of the ulcers, particularly that on the left mandible, resembled lesions of pyoderma gangrenosum. A skin biopsy was performed on an ulcer on the chest. Histopathologic examination revealed granulomatous dermatitis with multiple budding yeast forms, predominantly within histiocytes, with few organisms residing extracellularly. Methenamine silver stain confirmed the presence of 2-4 microm fungal spores suggestive of Histoplasma capsulatum (Fig. 2). Because of the patient's deteriorating condition, intravenous amphotericin B was initiated after tissue culture was obtained. Within the first week of treatment, the skin lesions started to resolve. Histoplasma capsulatum was later isolated by culture, confirming the diagnosis. The patient was continued on amphotericin B for a total of 10 weeks, and was started on lamivudine, stavudine, and nelfinavir for her HIV infection during hospitalization. After amphotericin B therapy, the patient was placed on life-long suppressive therapy with itraconazole. Follow-up at 9 months after the initial presentation revealed no evidence of relapse of histoplasmosis.

Practical value of Ki-67 and p53 labeling indexes in stereotactic biopsies of diffuse and pilocytic astrocytomas.

OBJECTIVE: Stereotactic biopsies are increasingly being used for the diagnosis and grading of astrocytomas, and there is a growing need to obtain maximum information from these tissue samples. In everyday practice, p53 protein and Ki-67 immunohistochemical analyses are the most frequently used ancillary studies to aid in diagnosis and grading, but their exact role is not clearly established. This study was undertaken to evaluate the practical value of these markers in stereotactic biopsy samples from diffuse astrocytomas as well as pilocytic astrocytomas. Methods/Results.-We analyzed the Ki-67 (MIB-1) and p53 labeling indexes in the stereotactic biopsy specimens from 11 pilocytic astrocytomas; 8 grade 2, 15 grade 3, and 16 grade 4 diffuse astrocytomas. Pilocytic astrocytomas and diffuse astrocytomas were evaluated as 2 separate groups. There was a strong correlation with poor outcome when both labeling indexes were higher than 15% in the same tumor for diffuse astrocytomas (P < 0.01). The indexes did not correlate with outcome in pilocytic astrocytomas. CONCLUSION: Combined Ki-67 and p53 labeling indexes higher than 15% indicated a worse outcome than suggested by the histologic grading. The analysis aided or improved histologic evaluation of stereotactic biopsies in our patients. We believe that a realistic prognostic upgrading of diffuse astrocytomas should be made only when labeling indexes for both markers are greater than 15%.

Pemphigus vegetans-Neumann variant associated with intranasal heroin abuse.

Pemphigus vegetans is variant of pemphigus vulgaris accounting for 5% of all patients with pemphigus disorders. We describe a case of pemphigus vegetans-Neumann type associated with intranasal heroin abuse, restricted to the modified mucous membranes. The results of routine histology and direct and indirect immunofluorescence studies confirmed the diagnosis. The patient responded to oral prednisone of 40 mg daily for 1 month, followed by reduction to a maintenance dose of 15 mg daily. A complete remission was sustained for 6 months. The relationship between intranasal heroin use and the development of pemphigus vegetans remains uncertain but appears to be an intriguing possibility in this patient.

Periumbilical pseudoxanthoma elasticum associated with chronic renal failure and angioid streaks--apparent regression with hemodialysis.

Pseudoxanthoma elasticum (PXE) is a heritable connective tissue disease involving progressive fragmentation and dystrophic calcification of elastic fibers. Periumbilical disease as the exclusive site of cutaneous involvement is most commonly seen in the rare entity termed periumbilical perforating pseudoxanthoma elasticum (PPPXE). Patients with this disorder are generally obese, middle aged, multiparous black women with hypertension. The cutaneous lesions are well-demarcated, hyperpigmented, periumbilical plaques with keratotic papules on the periphery. Extracutaneous manifestations have rarely been described. We describe a patient with periumbilical PXE associated with chronic renal failure and bilateral angioid streaks. Histopathologic examination demonstrated typical calcification of elastic fibers with additional amorphous calcium deposits in the superficial dermis. Transepidermal elimination was not present. Normalization of the serum calcium-phosphate product resulted in regression of the lesions--both clinically and histopathologically. The relation between PPPXE and hereditary PXE is discussed. The role of chronic renal failure in precipitating PPPXE is considered.

Rheumatoid papules in a patient with acquired immune deficiency syndrome and symmetric polyarthritis.

We describe a patient with acquired immunodeficiency syndrome (AIDS) and an unusual rheumatoid factor-positive symmetric inflammatory polyarthritis who met all 7 American College of Rheumatology criteria for RA, but who also had many features suggestive of seronegative inflammatory arthritis. Although cutaneous vasculitis has also been described in human immunodeficiency virus infection, this is the first report of cutaneous extravascular necrobiotic granuloma (rheumatoid papule) in AIDS. This case highlights the immunopathogenesis of inflammatory arthritis in AIDS and illustrates the difficulties in making a classic rheumatic diagnosis in the setting of the immune dysregulation caused by AIDS.

Hypopigmented variant of mycosis fungoides: demography, histopathology, and treatment of seven cases.

BACKGROUND: Hypopigmented macules have been described infrequently as a presenting form of mycosis fungoides (MF). OBJECTIVE: This study was designed to clarify general characteristics of a hypopigmented MF variant. METHODS: Seven new cases were investigated with the use of descriptive epidemiology techniques. Demographic parameters, histopathology, and treatment outcomes were analyzed. These data were combined with those from prior reports to develop a broad composite view of this disease process. RESULTS: The median ages in our series were 36 years for disease onset and 39 years at biopsy diagnosis. All patients had brown or black skin. Histologic findings consistently showed a lack of epidermal atrophy and moderate to profound exocytosis. Treatment with PUVA induced rapid and complete repigmentation in six of seven patients. CONCLUSION: On the basis of our experience and a literature review, the hypopigmented variant of MF occurs in a younger population than typical forms of the disease and affects persons with dark skin almost exclusively. Microscopic features include lack of epidermal atrophy and moderate to extreme epidermotropism of infiltrating mononuclear cells. The treatment of choice appears to be PUVA.

Infantile (desmoid-type) fibromatosis.

Infantile (desmoid-type) fibromatosis is an uncommon, locally aggressive tumor that is seldom reported in the dermatologic literature. We describe a case of infantile (desmoid-type) fibromatosis in a 2-year-old girl. Surgical disposition entailed amputation of the affected digit. Our report is intended to heighten awareness of this potentially fatal tumor, and emphasize the importance of timely diagnosis and treatment.

Nonnasopharyngeal lymphoepitheliomas (undifferentiated carcinomas) of the upper aerodigestive tract.

Lymphoepitheliomas are malignant tumors of epithelial origin with various amounts of reactive lymphocytic infiltrate. Although initially described in the nasopharynx (World Health Organization type 3 nasopharyngeal carcinoma), these tumors have been identified in various locations throughout the body. A strong association with Epstein-Barr virus (EBV) infection has been established for the nasopharyngeal type. Outside the nasopharynx, lymphoepitheliomas are exceedingly rare in the upper aerodigestive tract, with only isolated case reports of tumors in the larynx, trachea, and hypopharynx. This article features a rare case of lymphoepithelioma of the pyriform sinus. Furthermore, serologic testing, as well as in situ tumor DNA amplification (using the polymerase chain reaction) and hybridization techniques, demonstrated an association of this lesion with EBV infection. The characteristic histopathologic features common to this disease entity are presented, and the literature is reviewed with regard to lymphoepitheliomas of the upper aerodigestive tract outside the nasopharynx. Association of lymphoepitheliomas with EBV infection will be discussed.

Automated Speech-recognition Anatomic Pathology (ASAP) reporting.

Artificial intelligence speech-recognizers integrated with Laboratory information and Telefaxcommunication Systems have allowed for totally automated surgical pathology reporting. Automated Speech-Recognition Anatomic Pathology (ASAP) reporting improves the speed, text accuracy, comprehensiveness, and workflow management of diagnostic reports while eliminating support personnel. Healthcare reform goals of increased productivity and economy are furthered. Reports are rendered "as soon as possible" (ASAP) expediting appropriate clinical management and decreased length of stay and hospital costs.

Multicentric granular cell tumor of the heart presenting with aortic dissection.

A 43-year-old woman with a history of cutaneous granular cell tumor presented with severe aortic regurgitation due to a type A aortic dissection. During repair, multiple masses were found on the surface of the heart, which later were identified to be granular cell tumor. We present an extremely rare case of multicentric granular cell tumor of the skin and heart, manifested over a 23-year period.

Human papillomavirus type 16 in a homosexual man. Association with perianal carcinoma in situ and condyloma acuminatum.

BACKGROUND: The association of anal carcinoma with human papillomavirus (HPV) type 16 infection is well documented. Anal carcinoma is also frequently associated with a history of anogenital condylomata. More than 90% of anogenital condylomata contain HPV type 6 or 11. It is rare for a condylomatous lesion to contain HPV 16. We report the unusual case of a homosexual man, testing positively for human immunodeficiency virus, with carcinoma in situ evolving within perianal condylomata infected with HPV 16. OBSERVATIONS: Microscopic examination of tissue specimens from ulcerated verrucous lesions on the perianal mucosa revealed changes of classic condylomata acuminata with contiguous focal squamous cell carcinoma in situ. Testing for HPV DNA by in situ hybridization identified HPV 16 in both the condylomatous and carcinoma in situ areas. CONCLUSIONS: The association of HPV 16-infected condylomata and adjacent carcinoma in situ implies that cutaneous genital condylomata may progress to high-grade lesions. Given that homosexual men are at high risk for perianal carcinomas, HPV typing of perianal condylomata specimens may help identify immunocompromised patients who are at risk for the development of carcinomas.

Metastasizing thymoma and myasthenia gravis. Favorable response to glucocorticoids after failed chemotherapy and radiation therapy.

Myasthenia gravis (MG) occurs in up to 44% of patients with thymoma. Thirty-three percent of these neoplasms are invasive but extrathoracic disease is rare. Recently, we saw a patient with MG and recurrent, metastasizing mixed lymphoepithelial thymoma, whose disease was resistant to combination chemotherapy and radiotherapy but who responded dramatically to treatment with daily glucocorticoids. Thus, therapy with daily glucocorticoids should be considered in the treatment of invasive or metastatic thymoma associated with MG, including when conventional surgery, radiotherapy, and chemotherapy have failed.

Prognosis in infiltrating lobular carcinoma. An analysis of "classical" and variant tumors.

A precise histologic and clinical delineation of infiltrating lobular carcinoma, including its variant forms, has been elusive. We studied 230 patients with stage I and II infiltrating lobular carcinoma treated by mastectomy and axillary lymph node dissection. Included were 176 patients with the "classical" or "Indian-file" pattern (IFL) of infiltrating lobular carcinoma, and 54 patients with variant (VAR) histology [solid (SOL), alveolar (ALV), and mixed (MIX) patterns]. IFL patients were younger than VAR patients (52 versus 57 years; p = 0.004), and IFL patients were more likely to be premenopausal (p = 0.013). Microscopic multifocality and intraepithelial ductular extension of LCIS were both more frequent in the IFL group (p = 0.008 and 0.03, respectively). There was no significant difference in tumor size (T1 versus T2), axillary lymph node status, or TNM stage at presentation. Median survival time and time to recurrence was similar in the two groups. Although it was not statistically significant, median survival for stage I and low-axillary lymph node positive stage II IFL patients was better than that of VAR patients. One hundred forty of our 176 IFL patients (80%) could be matched with infiltrating duct carcinoma (IFDC) patients of similar age at diagnosis, menstrual status, tumor size, and axillary lymph node involvement. When stratified by stage, stage I IFL patients had a significantly higher disease-free survival (p = 0.02) than comparable patients with IFDC. There was not a significant difference in disease-free survival when stage II IFL and IFDC patients were compared. The unmodified term "infiltrating lobular carcinoma" should be restricted to lesions exhibiting the classical or Indian-file (IFL) microscopic architectural pattern in approximately 85% of the tumor. Patients with VAR forms of IFL may have a less favorable prognosis and should be distinguished from those with classical IFL for further characterization.

Non random cytogenetic changes characterize Merkel cell carcinoma.

Merkel cell carcinoma is a rapidly proliferating neoplasm of neuroectodermal origin presenting in skin. Karyotypes obtained in direct preparations of three Merkel cell carcinomas were analyzed and compared with six other tumors which were reported in the literature. Of the nine tumors studied so far, eight (89 per cent) showed structural abnormalities of chromosome 1. These abnormalities were in the form of trisomy for chromosome 1q22----ter. Furthermore, it was also observed that the breaks of these rearrangements on chromosome 1 occurred at the bands to which c-oncogenes N-ras (p31), L-myc (p32), c-src (p36), c-ski (q22-22), and the beta-subunit of the nerve growth factor (NGF) (p22) were localized. In addition to structural changes, five out of the nine tumors (55.5 per cent) were trisomic for chromosome 1. Merkel cell tumors are often confused with small cell carcinoma of lung or peripheral neuroepithelioma. The cytogenetic abnormalities such as rearrangement of chromosome 3p and t(11;22)(q23;q12) which characterize lung carcinoma and peripheral neuroepithelioma, respectively, were not seen in any of the nine Merkel cell tumors studied. Thus it appears that rearrangement of chromosome 1 was non-randomly associated with Merkel cell carcinoma. It is of interest to note that genes involved in neuronal development and or differentiation have been mapped to the bands at which breaks occurred in these tumors. The significance of these changes is briefly discussed.

Primary malignant melanoma of the esophagus.

Primary malignant melanoma of the esophagus is exceedingly rare. We identified six patients seen at Memorial Hospital for Cancer and Allied Diseases over a period of 35 years. All patients were Caucasian, with an age range of 30 to 74 years (mean: 60 years). There were three men and three women. No association was noted with tobacco or ethanol use, nor was there a personal or family history of malignant melanoma. Symptoms were related to obstruction or hemorrhage. All tumors were polypoid and had attained large size at the time of initial diagnosis. Histologically, the melanomas had epithelioid, spindle-cell, and pleomorphic areas with focal melanin production. An intraepithelial "in situ" component was present in five cases and melanosis of the non-neoplastic esophagus in five. All six neoplasms were immunoreactive for S-100 protein, and none reacted with anticytokeratins. Two cases examined ultrastructurally showed premelanosomes. All patients were treated by esophagogastrectomy. The mean survival for four patients was only 2.1 months. The two remaining patients are alive at 5.5 and 11 months.