Correct Pathological Diagnosis Research Articles

77 The Pathological Disease Spectrum of Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) in Sudden Cardiac Death Emphasising Biventricular Involvement and Challenges in Diagnosis

<h3>Introduction</h3> Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disease of the heart muscle characterised by fibrofatty replacement of the myocardium. It is a major cause of sudden death in the young, specifically athletes. ARVC is largely a genetic disease with implications for living family members and cardiological screening. We present the largest detailed pathological study from the UK of arrhythmogenic right ventricular cardiomyopathy (ARVC) diagnosed at post-mortem following sudden death. <h3>Methods and results</h3> We identified 121 cases of sudden cardiac death due to ARVC in our UK referral sudden death database. Cases were identified using our database compiled from 2873 sudden cardiac death cases received in our specialist national referral centre between 1994 and 2012. This study highlights clinical history, initial pathological opinion, macroscopic and microscopic findings on specialist examination. Individuals were predominantly male (82%) from 8–66 years with highest prevalence at 21–30 years. Cardiac arrest occurred mainly during/immediately after exertion (45%) and at rest (38%). Macroscopic examination showed dilatation of right atrium and ventricle with thinning (44%) and dilatation of left atrium and ventricle (19%). There were pale areas with fat replacement of epicardial muscle in both ventricular walls (70%) and septum (12%). The right ventricular outflow tract (RVOT) was involved in all biventricular cases. Left ventricular hypertrophy showed increased epicardial fat (49%) and right ventricular fatty hypertrophy (15%). 12% were macroscopically normal. Thrombi in the right ventricle occurred in 10% of cases. Histologically fibrofatty replacement with degenerate myocytes was seen in all cases, Biventricular disease predominated (78%). Above the midventricle there was always involvement of the epicardial surface of RVOT. Left ventricular involvement was epicardial and circumferentially with predominant involvement of the posterobasal wall. The biventricular disease cases had left dominance in 21% or right dominance in 17%. Of the 53 opinions by referring pathologists, only 27 were identified as ARVC highlighting the difficulty of diagnosis. <h3>Conclusion</h3> ARVC ranges from normal appearing hearts to widespread biventricular disease. ARVC has genetic implications and correct pathological diagnosis is vital to ensure that family members at risk are screened to prevent further sudden deaths.

Clinicopathologic characteristics of esophageal primary malignant melanoma

Malignant melanoma is a rare tumor that commonly occurs in the skin; however, it can also develop in other sites, including the esophagus, oral cavity, sinonasal tract, anorectal region, vagina, and eye. Esophageal primary malignant melanoma (EPMM) accounts for approximately 0.2–0.3 % of all malignant esophageal tumors. The mean age of patients who develop EPMM is 61 years (range 21–90 years). EPMM predominantly affects males (male to female ratio 2.4:1). The tumor preferentially occurs in the lower and middle part of the thoracic esophagus and commonly appears as a polypoid mass. Histologically, it is composed of polygonal or spindle cells with atypical nuclei and varied amounts of melanin pigment in the cytoplasm. Immunohistochemical stains for S-100 protein, HMB-45, and Melan-A are useful for a correct pathological diagnosis. EPMM often has scattered lesions and occasionally melanocytosis around the main tumor. EPMM and malignant melanomas occurring in other organs exhibit aggressive biological behavior. A review of autopsy cases indicates that EPMM commonly metastasizes to the lymph nodes (82 %), liver (72 %), lung (69 %), peritoneum (45 %), and bone marrow (41 %). Although improved survival with the molecular targeting agent vemurafenib has been demonstrated in cutaneous melanoma with BRAF V600E mutation, recent evidence indicates that EPMM has genetic alterations unique from those observed in cutaneous and other mucosal melanomas. Since information regarding the genetic features of EPMM is limited, further progress in understanding the molecular pathology of this disease is required for the development of novel therapeutic strategies. This paper aims to review previously reported EPMM cases to clarify its clinicopathologic features that could aid in the development of effective therapeutic strategies.

Core Biopsy Diagnosis of Adenomatoid Hyperplasia of Minor Salivary Gland

Adenomatoid hyperplasia (AH) of minor salivary gland is as such as an unusual entity. Clinically it simulates pleomorphic adenoma. Core biopsy and meticulous histopathological examination can be used as an effective diagnostic tool to arrive at correct pathological diagnosis. Herein, we are reporting a similar interesting case diagnosis of which was done on core biopsy.

A case-report of synchronous adenocarcinoma and gastrointestinal stromal tumor of the colon

Synchronous colonic tumors of different morphology are rarely described in the literature and do not have a clear ethiological connection. This fact is the key to a more detailed study of the clinical and morphological and molecular genetic features of different gistotipov synchronous tumors. There is increasing publications and clinical observations of simultaneous coexistence of adenocarcinoma and gastrointestinal stromal tumor. A separate and very valuable space is given interaction surgeons oncologists and pathologists. Today, for the correct pathological diagnosis of synchronous tumors of different biological nature, it is obligatory to conduct immunohistochemical study. Data on the results of treatment of synchronous tumors must necessarily be recorded in the cancer registries. Based on that, the developed algorithms timely diagnosis and proper treatment strategy in the cohort of patients. We present a case report of a 56 year old patient with a rare synchronous epithelial and non-epithelial colon tumors.

Malignant peripheral nerve sheath tumor of proximal third tibia

A 16-year-old man had aswelling over the anterior aspect of the proximal third of the tibia for 1 year, which was peanut size initially and progressively increased to its present size of 10 cm × 8 cm. He underwent fine needle aspiration cytology (FNAC) twice during this period and reported aspindle cell sarcoma. Malignant peripheral nerve sheath tumor (MPNST) is a malignancy of the connective tissue surrounding the nerves. Previously, MPNST was also known as neurofibrosarcoma, malignant schwannoma, andneurogenic sarcoma. We are reporting this case for its rarity and peculiar mode of presentation. FNAC/core biopsy can be used as an effective tool to achievethe correct pathological diagnosis.

Epithelial borderline ovarian tumor: Diagnosis and treatment strategy.

Epithelial borderline ovarian tumors (BOT) are distinctive from benign tumors and carcinoma. They occur in younger women more often than carcinoma, and there is some difficulty making correct diagnosis of BOT. Two subtypes of BOT, serous and mucinous borderline tumor have different characteristics and very different clinical behavior. Serous borderline tumor (SBT) with micropapillary pattern shows more incidence of extra ovarian disease and often coexists with invasive implant. SBT with micropapillary pattern in advanced stage has showed a worse prognosis than typical SBT. Huge mucinous borderline tumors have histologic heterogeneity, and the accuracy of frozen section diagnosis is relatively low. Extensive sampling is required to reach a correct pathological diagnosis. Mucinous adenoma (intestinal type) also runs the risk of recurrence after cystectomy, or intraoperative rupture of cyst. Laparoscopic procedure for BOT has not increased the risk of recurrence. Fertility preserving procedures are generally accepted, except in advanced stage SBT with invasive implants. Only cystectomy shows a significant risk of recurrence. Re-staging surgery and full staging surgery is not necessary for all BOT. We should not attempt to treat them uniformly, by the single diagnosis of "borderline tumor". It depends on histologic type. Close communication with the pathologist is necessary to gain more detail and ask more pathological samples in order to make the optimal treatment strategy for each individual patients.

Acquiring diagnostic experience in placenta pathology through HIPON web course

Aim The correct evaluation of microscopic features, a mandatory step for the correct pathologic diagnosis, reflects professional experience well worth acquiring by trainees in Pathology. This is the target of HIPON, a project co-financed by the Lifelong Learning Program of the EACEA, EU Commission. Methods We present our educational strategy as already implemented on the HIPON online chapter of placenta pathology. The diagnoses and differential diagnoses of representative cases of vascular and inflammatory placenta diseases are analysed step by step through microscopic images. A virtual slide of a placenta section with typical maternal and fetal vascular changes is available to the user. Results After becoming familiar with the principles of placental pathology, the user learns to identify the basic entities related to vascular and inflammatory placental disease. This knowledge is consolidated by an image-based test, the resources, the links and the glossary of this chapter. Discussion The concept of HIPON is to follow mixed learning pathways, supported by a rich variety of components of the ICT System (virtual portfolio, e-modules, online game, histo-book) and a mass amount of case data, in order to provide practical experience, essentially bridging the worlds of education and professional practice.

P1–070 - Significance of Renal Mass Biopsy for Deciding the Treatment Strategy of Renal Tumor

Introduction: We sometimes encounter difficult cases for diagnosis of renal mass because of the lack of typical findings of RCC in imaging studies. We have been performing percutaneous needle biopsy of renal mass for indicated cases to obtain the pathological diagnosis and to decide treatment strategy of renal tumor. We report our experience of renal mass biopsy to examine its utility in the diagnosis and management of renal tumor. Materials and methods: Since 2008, we have performed percutaneous needle biopsy of renal mass in 17 patients. Indications of tumor biopsy are histological diagnosis between RCC and non-RCC, and histological diagnosis of clear cell RCC versus non-clear cell RCC in patients with poor performance status or advanced disease in whom upfront primary surgery was considered impractical. If imaging studies suggested the presence of tumor necrosis, we combined intraoperative frozen section pathology for diagnostic accuracy. Results: Median age was 69 (51-80) years old. Ultrasonography (US) and computerized tomography (CT) guided biopsies were performed in 15 and 2 patients, respectively. Pathological diagnosis was RCC in 12 patients and urothelial carcinoma (UC) in 5. Diagnostic discrepancy was noted in 2 patients, each of whom was diagnosed RCC in CT scans but were histologically diagnosed UC by tumor biopsy. Among 12 patients who were histologically diagnosed RCC, clear cell type was noted in 7 patients and non-clear cell type in 5. Intraoperative frozen section pathology was used for 5 patients who exhibited necrosis within the renal tumor on CT scans. Biopsy-related adverse events were noted in 2 cases. One case developed needle tract implantation and died 3 months after nehroureterectomy for UC. The other patient, in whom intraoperative frozen section pathology was not used, had failed histological diagnosis because of only necrotic tissue in biopsy specimens. Conclusions: Treatment strategy of metastatic RCC is different depending on histology and risk classification. Correct pathological diagnosis by US or CT guided needle biopsy of renal tumor contributes to appropriate use of molecular-targeted drugs for patients with metastatic RCC. In addition, we can differentiate RCC from UC. Renal tumor biopsy should be considered as diagnostic test for indicated cases.

Outside Slide Review in Gynecologic Oncology

In gynecologic oncology, surgical and adjuvant therapy rely heavily on correct pathologic diagnosis. Thus, in-house review of outside pathologic slides and specimens has become routine within large tertiary referral centers. We sought to determine the impact of outside pathologic slide review on gynecologic oncology patient care and treatment. Gynecologic oncology cases between January 2007 and January 2012 were evaluated. Clinical information was gathered from comprehensive chart reviews and reports created after multidisciplinary treatment planning conferences. Discrepancies in diagnosis were identified as major if they resulted in a treatment alteration and minor if they did not impact care. Data were analyzed using descriptive statistics and the Fisher exact test. A total of 279 cases were identified and reviewed as part of the study--126 (45.2%) biopsy/cytology specimens and 153 (54.8%) surgical excision specimens. Minor discrepancies were noted in 25 reviewed cases (9%) and major discrepancies in 19 cases (6.8%). Among those patients in whom management was changed based on specialized pathologic review, 50% underwent additional surgery, 16% had their surgical plan modified, and 16% received adjuvant treatment or had their adjuvant treatment modified. In 235 cases (84.2%), institutional rereview of the outside slides/specimens did not result in a change in diagnosis. Diagnostic discrepancies were evenly distributed across all primary sites evaluated. The cost of outside pathologic review was estimated at $2,936 US dollars per change in diagnosis. Mandatory slide review in gynecologic oncology is important and results in diagnostic changes in approximately 16% of cases, with 43% of those changes impacting treatment.

Vertebral Bone Primary Angiosarcoma: A Case Report

Primary vascular tumors of the vertebral bones are extremely unusual1, comprising <1% of all bone neoplasms1, 2. Their diagnosis is often challenging because of their clinical presentations vary from totally asymptomatic to extremely aggressive2. Another problem associated with these tumors is the great confusion around their terminology; this problem has been resolved with the restriction of the term “hemangioendothelioma” to soft tissue lesions with a low degree of malignancy only1, 3. The term “epithelioid hemangioendothelioma”, which was first introduced by Weiss and Enzinger to denote a group of soft tissue tumors, has been used many times since to incorrectly categorize bone tumors1. The correct pathological diagnosis of these neoplasms is a priority because it is essential to the rapid selection of an effective management plan. We here describe a case of a primary vertebral angiosarcoma and present a concise review of the more relevant diagnostic aspects.

Diagnostic performance of CMR and transthoracic echocardiography in clinical evaluation of cardiac masses with histopathological correlation

Echocardiography is the preferred initial imaging method for assessment of cardiac masses. However, CMR, with its excellent tissue characterization and wide field of view, can provide unique information in the evaluation of cardiac masses. Our objective was to identify CMR and echocardiographic parameters that predict the presence of tumor or malignancy in biopsy proven cardiac masses and to assess the potential added value of CMR to echocardiography in the evaluation of cardiac masses. Methods We retrospectively identified 50 patients (50% male, mean age 46 ± 17 years) referred for CMR evaluation of cardiac mass who underwent biopsy or resection with histopathological diagnosis. Echocardiography was performed prior to CMR in 44/50 (88%) of the cases. Echocardiographic and CMR characteristics of the mass were evaluated for their predictive value in distinguishing tumor versus non-tumor and malignant versus non-malignant masses based on histopathology as the gold standard. Tumors were classified as any benign or malignant (primary or metastatic) neoplasm found in or around the heart while non-tumors were classified as any other mass (eg, thrombus) found in this area.Binary logistic regression and ROC curves were used to assess the diagnostic utility of these imaging characteristics alone and in combination for prediction of tumor or malignancy. Wilcoxon rank-sum test was used to compare the number of times a correct pathologic diagnosis was provided by each imaging study.

Endoscopic Resection. Aspects of Technique and Optimization of Outcomes. Current Indications to PDD-Guided Resection

Trans-Urethral Resection (TUR) of bladder tumors is the gold standard to make the correct diagnosis and remove all visible lesions. The strategy of resection depends on the size of the lesion. Small tumors can be resected en bloc, while larger tumors should be resected separately in fractions to obtain a correct pathological diagnosis. Random biopsies from normal-looking mucosa should be performed in patients with positive urinary cytology and absence of visible tumor in the bladder. As a standard procedure, cystoscopy and TUR are performed using white light. Photodynamic diagnosis (PDD) is most useful for detecting CIS, and therefore should be restricted to those patients with a suspected high-grade tumor.

What is New in Rhabdomyosarcoma Management in Children?

Optimal management of rhabdomyosarcoma requires establishing the correct pathologic diagnosis, histologic sub-type, primary site, extent of disease (Stage), and extent of resection (Group). Based on these features, cooperative groups in North America and Europe have defined risk-adapted treatments that include surgery, chemotherapy, and usually radiotherapy. This article focuses on recent findings that can impact or have already impacted rhabdomyosarcoma treatment guidelines and highlights controversies that should be addressed in order to improve outcome for children with rhabdomyosarcoma. Rhabdomyosarcoma is currently sub-classified in children based on histology into the favorable embryonal/botryoid/spindle cell types and the unfavorable alveolar form. Risk group assignment depends in part on histologic sub-type. Alveolar rhabdomyosarcoma is sometimes associated with chromosomal translocations, which impact clinical behavior. An important ongoing debate is whether molecular diagnostic tools to identify chromosomal translocations and/or define gene expression profiles should be used to sub-classify rhabdomyosarcoma rather than histology. Clinical trials continue to evaluate retrospective as well as prospective cohorts in order to carefully determine the impact of histology versus biologic features on outcome in the context of specific therapeutic regimens. Most rhabdomyosarcoma recurrences involve the primary site or adjacent region. Cooperative groups continue to investigate new approaches to local control in order to reduce local recurrences and sequelae associated with local therapy. Delaying primary resection until after chemotherapy has started appears to increase the number of tumors that can be completely resected with acceptable morbidity in some primary sites. Radiation dose reductions following delayed primary resection have been investigated. Although outcomes appear similar to the conventional approach of full-dose radiotherapy without delayed primary resection, long-term effects of the two approaches have not been rigorously compared. Early evidence suggests that newer methods of delivering radiotherapy, including intensity-modulated radiotherapy (IMRT), proton beam radiotherapy, and brachytherapy maintain efficacy but may reduce long-term sequelae compared with 3-dimensional conformal radiotherapy. Chemotherapy regimens defined by the cooperative groups vary by risk group. The most commonly used regimens include vincristine and dactinomycin in combination with an alkylating agent, either cyclophosphamide or ifosfamide. In order to improve outcomes, recent clinical trials have introduced new chemotherapeutic agents (e.g. topotecan, carboplatin, or epirubicin) into the treatment regimens. However, outcomes have not been significantly impacted. Novel chemotherapy administration schedules have been tested in patients with metastatic rhabdomyosarcoma, including interval compressed dosing or maintenance therapy, and may be promising. Molecularly targeted agents are currently under investigation in combination with chemotherapy for patients with recurrent or metastatic rhabdomyosarcoma. It is hoped that these novel agents will benefit all patients with rhabdomyosarcoma in the future.

Pancreatic Cysts Fluid Analysis: CEA, Cytology, and K-Ras

Purpose: Accurate diagnosis of a pancreatic cyst is often difficult. A number of methods have been employed utilizing EUS/FNA, including analysis of cyst fluid for CEA, cytology, and more recently K-Ras gene mutation. K-Ras mutation has been shown to be the most specific of these, but not very sensitive. Often, a cyst aspirate can only be sent for one or two of these three markers due to limited amount of fluid within the cyst. The purpose of this study is to identify the combination of markers which would provide the best chance for the correct diagnosis. Methods: After obtaining IRB approval, we obtained the medical record numbers of all patients seen at UMMHC from October 2003 through December 2011 who were coded with ICD-9 code 577.2, which represents the diagnosis of pancreatic cyst or pseudocyst. Of these, we included in our study those cases that had K-Ras analysis and/or came to a definitive diagnosis (surgical pathology). We then compared the utility of different cyst fluid markers (and their combinations) in making the correct pathological diagnosis. Results: We identified 111 unique cases, and 61 cases which were repeat EUS/FNA procedures, for a total of 172 cases. The Table below summarizes the results. Our results revealed that the combination of K-Ras gene analysis and cytology has the best sensitivity and accuracy, and is tied for the best specificity, positive predictive value, and negative predictive value.Table: No Caption available.Conclusion: Our results suggest that analyzing the cyst fluid for the K-Ras mutation and cytology gives the best chance of making the correct diagnosis. One of the problems with cytology is that the aspirate is often non-diagnostic due to the acellular nature of the cyst. Before abandoning CEA testing, a larger study needs to be performed to confirm these results. Additionally, improving cytology yields can further enhance the utility of combining these two markers.

Rosai-Dorfman Disease with Isolated Laryngeal Involvement

Rosai-Dorfman disease is a rare histiocyte disorder that is typically characterized by massive cervical lymphadenopathy. Isolated extranodal involvement is uncommon, and isolated laryngeal involvement is extremely rare. We report an unusual case of Rosai-Dorfman disease with isolated laryngeal involvement that led to recurrent dysphonia and airway obstruction. We discuss the challenges we faced in reaching a correct pathologic diagnosis and in deciding on an appropriate treatment regimen. Based on our experience, we believe that Rosai-Dorfman disease should be considered as a differential diagnosis in patients who present with a recurrent inflammatory (histiocytic) mass lesion of the larynx.

Desmin and CD34 positivity in cellular fibrous histiocytoma: an immunohistochemical analysis of 100 cases

Cellular benign fibrous histiocytoma (CBFH) represents a morphologic variant of cutaneous fibrous histiocytoma (FH). Because of its relative monomorphism and frequent fascicularity, CBFH can easily be mistaken for a malignancy. In fact, CD34, often used to distinguish CBFH from dermatofibrosarcoma protuberans (DFSP), can also be positive. To add to the confusion, desmin positivity may also be observed in a subset of CBFH. Desmin and CD34 expression often cause interpretative difficulty which may lead to misdiagnosis. Our aim was to examine the incidence of desmin and CD34 expression in CBFH. One hundred consecutive cases of morphologically typical CBFH were retrieved from consultation files. Clinicopathologic and immunohistochemical features were evaluated. SMA positivity was found in tumor cells in 93 of 100 cases (93%). Desmin positivity was found in 32 of 100 cases (32%). CD34 was positive in 6 of 100 cases (6%). There was no evident correlation between immunophenotype and anatomic site or other clinical variables. Frequent desmin (32%) and occasional CD34 (6%) expression are encountered in CBFH. Desmin positivity can be explained on the basis of myofibroblastic differentiation. The occasional CD34 positivity in a subset of CBFH should not be a deterrent from making the correct pathologic diagnosis, based on characteristic morphologic features.

Uterine sarcomas: a multidisciplinary challenge

With an incidence lower than 1/100,000/year, uterine sarcomas are a rare subgroup within the rare family of sarcomas, giving rise to 1% of female malignancies. However, they are a variegated set of malignancies, encompassing leiomyosarcomas, endometrial stromal sarcomas, undifferentiated endometrial sarcomas and adenosarcomas [1]. Another group, malignant mixed mesodermal tumours, are currently regarded as metaplastic (aggressive) endometrial carcinomas, i.e. epithelial tumours in nature, not sarcomas [2]. Both the low incidence and the heterogeneity of uterine sarcomas pose their first multidisciplinary challenge, inasmuch as a correct pathological diagnosis is crucial to proper management. Even the differential diagnosis between benign and malignant tumours can be problematic. One may recall the existence of a distinct entity among smooth muscle tumours, i.e. smooth muscle tumours of uncertain malignant potential (STUMP), whose behaviour is by definition unpredictable pathologically, and of benign metastasising leiomyoma and disseminated peritoneal leiomyomatosis, i.e. benign smooth muscle tumours presenting with metastatic dissemination [3]. Improvements in the pathological classification, and grading systems, for all these tumours are highly necessary. Endometrial stromal sarcomas are low-grade malignancies, although the relapse rate after surgery of localised disease is relatively high, possibly amounting to one third of cases, although over a long period. Pathologically, these tumours are marked by their positivity for oestrogen and progesterone receptors. This underlies the efficacy in the advanced disease setting of progestins, aromatase inhibitors and gondadotropin-releasing hormone analogues [4]. Responses are frequent and long-lasting, also owing to the natural history of these tumours, even when metastatic. For this reason, surgery of lung metastases is an option to consider within a multidisciplinary approach. The usefulness of adjuvant hormonal therapies is still an open issue, given the relapse rate and the hormonal sensitivity of these tumours [5]. Bilateral oophorectomy, in addition to total abdominal hysterectomy for local treatment, also has an adjuvant intent. Currently, endometrial stromal sarcomas are conceptually separated from undifferentiated endometrial sarcomas, although a de-differentiation process of some endometrial stromal sarcomas into high-grade sarcomas may occasionally take place [6]. Undifferentiated endometrial sarcomas are inherently high-grade malignancies (pathologically marked by a high mitotic rate, cellular pleomorphism and necrosis), which are insensitive to hormonal therapy and clinically aggressive. This considered, an aggressive, multidisciplinary approach to this rare entity is logical. Medical therapy must resort to standard agents for high-grade softtissue sarcomas. On the contrary, adenosarcomas are low-grade malignancies encompassing a benign epithelial component and a low-malignant mesenchymal one. Their good prognosis is unfavourably affected when a truly sarcomatous overgrowth or myometrial invasion is present [7]. Uterine leiomyosarcomas are cured in less than one half of cases by total abdominal hysterectomy, with size and pelvic extent as the main prognostic factors. Improvements in grading systems would be required, in order to refine the prognostic value of pathological assessment. Radiation therapy did not add to surgery alone in a large randomised trial [8], in spite of positive evidence provided by uncontrolled and retrospective studies as far as the local regional relapse rate is concerned [9]. This may leave room for individualised decision-making on radiation therapy in some cases, depending on the surgical outcome and anatomical considerations. Of course, radiation therapy can be useful in local regional relapses. The efficacy of adjuvant chemotherapy is an open issue in soft-tissue sarcomas, and therefore in uterine leiomyosarcomas as well. These are essentially insensitive to hormonal therapies, although hormonal receptors are found in the tumour tissue in a proportion of cases and there is anecdotal evidence of hormonal sensitivity in occasional patients. Medical therapy in the advanced disease resorts to agents active in

Infantile Melanoma—A Triple Threat

Cases of infantile melanoma are very rare, and only a few have been presented in the literature. Pediatric melanoma can present to the clinician as a "triple threat" of delayed diagnosis resulting in thick lesions at risk for metastasis, histologic uncertainty of diagnosis, and a lack of data guiding regional node management and adjuvant therapy. Melanoma in childhood is an uncommon condition, and it is even more atypical in infants. There is evidence however that it is increasing in frequency. We present 2 cases of infantile melanoma diagnosed before age 1 and multidisciplinary management performed at our institution. One child was diagnosed with melanoma arising within a congenital melanocytic nevus, and the other presented with melanoma from a de novo acquired scalp lesion. The ambiguity surrounding correct pathologic diagnosis of melanoma in this age group, and the tendency for late diagnosis with thicker lesions presents special staging and treatment challenges to the team of specialists involved in the care of these children.

Electromagnetic Navigational Bronchoscopy

The purpose of this study was to investigate the diagnostic yield and safety of electromagnetic navigation bronchoscopy (ENB) on peripheral lung lesions deemed otherwise unreachable using conventional bronchoscopy in high-risk patients. This was a retrospective chart review involving adults (age, 18 y and older) who underwent ENB for pulmonary lesions located at the fourth order of bronchi or beyond, including subpleural lesions, at the University of Chicago Medical Center. Forty-eight patients underwent ENB by 3 different trained operators from January 2006 to September 2008. There was a short period of inactivity when the device was withdrawn from the market. ENB was reserved for use only in lesions at the fourth order of bronchi or beyond, including subpleural lesions, in patients who are considered high risk for other invasive procedures. Pathologic, cytologic, and microbiologic studies were carried out on recovered samples. Postprocedural chest radiographs were obtained on all patients to detect the presence of procedure-associated complications. ENB led to the diagnosis of 37 of 48 (77%) lesions not amenable to conventional bronchoscopic biopsy in high-risk patients. Of the 37 successful procedures, malignancy was identified in 18 patients (49%). Nonsmall cell lung cancer (NSCLC) was diagnosed 16 times, whereas both small cell lung cancer and carcinoid tumor were diagnosed once. In addition, 4 lesions (11%) were found to be infectious, 1 lesion (3%) was found to be granulomatous (noncaseating), and 1 lesion (3%) was diagnosed as organizing pneumonia. Of the 37 successful diagnoses, 13 lesions (35%) were determined to be nonpathologic, benign lesions. Eleven procedures (22%) were unsuccessful in yielding the correct pathologic diagnosis. Nine of the 11 unsuccessful ENB cases (82%) were found to be malignant, 9 of which were identified as NSCLC. Other than NSCLC, 1 neuroendocrine tumor (9%) and 1 metastatic transitional cell carcinoma of the kidney (9%) were identified by alternative, invasive testing methods. The 2 other lesions unsuccessfully diagnosed by ENB were not malignant. One was determined to be infection (histoplasmosis) and the other was diagnosed as an organizing pneumonia. The most common complication noted by all modalities was pneumothorax. ENB carried a pneumothorax rate of 5 of 49 (10%), 2 of which required chest tube insertion for treatment. In the ENB success group, 4 cases (11%) were complicated by pneumothoraces. In the ENB failure group, 1 case (9%) was complicated by a pneumothorax. ENB is an effective and low-risk modality for diagnosing pulmonary lesions that are difficult to reach in patients deemed to be at high risk for invasive procedures. Although no clear criteria for the use of ENB currently exist, our study shows that diagnostic sampling can be obtained in 77% of lesions at the fourth order of bronchi or beyond, including subpleural lesions. ENB is an effective, minimally invasive method for the diagnosis of pulmonary nodules previously deemed unreachable by conventional bronchoscopy in high-risk patients and harbors a low complication rate.

Hodgkin's Lymphomas: A Tumor Recognized by Its Microenvironment

Thomas Hodgkin's and Samuel Wilks first recognized Hodgkin disease in the first half of the 19th century. Initially described as lymphogranulomatosis, it was later recognized to be a lymphoid neoplasm derived from B cells and was classified on the basis of its histopathological features. Hodgkin lymphomas are now regarded as encompassing two clearly defined entities according to the WHO classification: nodular lymphocyte-predominant Hodgkin Lymphoma (NLPHL) and classical Hodgkin Lymphoma (CHL). This paper focuses on the current knowledge about the biological features that characterize both NLPHL and CHL, highlighting those relevant to correct pathological diagnosis and those that might be associated with patient outcome.