Primary Rosai-Dorfman disease of the thymus and lung: A clinicopathological and immunohistochemical study of three cases.

Three cases of primary Rosai-Dorfman disease of the thymus and lung are presented. The patients are 3 men between the ages of 42 and 47 years who presented with non-specific symptoms including cough, chest pain, and shortness of breath. Clinically, the patients did not have any other pertinent clinical history. Diagnostic imaging revealed in one patient a cystic anterior mediastinal mass, while in two other patients the imaging was that of an intrapulmonary mass, one in the right upper lobe and the other in the left lower lobe. The three patients undergo surgical resection of the mass. In the cases in which the tumor mass was in the lung, both patients had a lobectomy while in the patient with anterior mediastinal mass, surgical resection via thoracotomy was performed. The intrapulmonary tumors were described as soft and yellowish measuring 2.5 and 3.0 cm in greatest diameter, while the mediastinal mass was described as cystic measuring 4.0 cm in diameter. Histologically, all tumors show similar features in terms of a proliferation of large histiocytes admixed with an inflammatory component composed predominantly of plasma cells. Immunohistochemical stains show positive staining for CD68 and S-100 protein, while negative for keratin, CD1a, and langerin. The cases herein presented highlight the ubiquitous distribution of Rosai-Dorfman disease and the importance of keeping this entity in the differential diagnosis of histiocytic proliferation in the thymus or lung.

Thymoma: Histologically a heterogenous group of tumors.

Over the years the nomenclature of thymomas has been debated regarding the best manner in which these tumors should be grouped. In every schema presented thus far, the main issue has been the presence or lack of lymphocytes and accordingly, the tumors have been place into a specific category. However, even though this concept applies for most of the cases, there are numerous tumors that do not necessarily fit into those categories as either the thymomas show another cellular proliferation associated with the epithelial cells or the epithelial cell themselves are arranged in a pattern that departs from the conventional features of the classic thymoma. Herein we will emphasize those features, which in some circumstances, mainly with small mediastinoscopic biopsies may pose a considerable problem in interpretation. We do consider that the most important issue is to be familiar with the different growth pattern that these tumors may show in order to avoid misdiagnosis. In addition, we consider that regardless of the growth pattern or cellular composition of the tumor, it is highly recommended that these tumors just like any other be carefully sampled and properly stage. Although we are fully aware of the different growth pattern and specific cellular details that thymoma may show, the discussion of each one of those tumors is beyond the scope of this review. Therefore, we have placed more emphasis in those, which in our judgment are more commonly encountered in the daily practice.

Multilocular thymic cyst (MTC) and other tumors with MTC features: Pitfalls in diagnosis.

Cystic lesions of the anterior mediastinum represent a well-known group of benign lesions that are relatively common in the general practice, namely in the pediatric age group. In the adult population, multilocular thymic cyst (MTC) plays an important role in occurrence as it presents as a cystic anterior mediastinal mass that clinically may mimic another anterior mediastinal tumor. In general, MTC is of rather unusual occurrence and its histopathological features have been well described in the literature. However, similar histopathological features may also be associated with a gamut of other tumoral conditions that although unrelated may be encountered growing along the walls of these cystic structures. Herein a presentation of the classical MTC and the classical histopathological features of such entity in association with other tumoral conditions will be discussed. It is highly important to underscore that the final interpretation of some of these tumors is based on a thorough evaluation of the cystic lesion and a reasonable sampling for histological evaluation so that the proper interpretation can be reached. Needless to say, the radiological and clinical information of the patients with cystic anterior mediastinal lesions is very important in the final analysis of these cases.

Thymoma: Challenges and Pitfalls in Biopsy Interpretation.

The interpretation of biopsy specimens in the diagnosis of thymoma is a subject that is generally not addressed in the literature. Even though the diagnosis of thymoma may seem to be an easy step in the assessment of these tumors, in reality, it is the biopsy specimen interpretation that will be use to determine course of action in any particular patient. It may determine whether a patient is a surgical candidate or on the contrary whether a patient may be benefited the most by medical therapy. In addition, there may be conditions in which all that is required is surgical resection without any further treatment, and that the evaluation of those conditions does not necessarily required the careful pathologic staging that thymomas need. In addition, it is important to highlight that in small biopsies, there are limitations not only in terms of the cellularity and other features that may not be present in such biopsy but also the limitation in term of immunohistochemical interpretation. Herein we have attempted to highlight numerous tumoral conditions that are frequently encountered in the daily practice of mediastinal pathology, some of them pose significant problems in separating them from thymomas. Needles to say, the entire spectrum of mediastinal pathology that may at any given time mimic thymoma is well beyond the scope of this review. Furthermore, we also herein emphasize the need for proper clinical and radiologic information and correlation in order to lead to a better interpretation of the biopsy specimen. The emphasis in this review is on thymoma and their possible pitfall and shortcomings while evaluating small biopsy specimens.

Incidentally discovered myelolipomatous adrenal adenomas, including six cases presenting with hypercortisolism.

Most adrenal incidentalomas are non-functioning adenomas that require no treatment. The presence of a myelolipomatous component of adrenal incidentalomas is a rare, but well-known occurrence in both hyperplastic and neoplastic lesions of the adrenal cortex. Although the improvements in abdominal imaging have increased identification of myelolipomatous adrenal cortical adenomas radiologically, due to the rarity of this lesion, the clinical pathological features of these lesions are unclear and can sometimes cause diagnostic difficulty. Eleven patients had surgeries at The University of Texas MD Anderson Cancer Center. Four additional cases were provided from an external collaborator. Of the 15 cases, there were 5 male and 10 female patients, with a median age of 52 years (mean 54 years, range 28-84 years). Clinical presentation included adrenal incidentaloma (n = 9), Cushing syndrome (n = 4, including 1 as a part of Carney complex), and subclinical Cushing syndrome (n = 2, including 1 with bilateral macronodular adrenal hyperplasia). In this study, we present the clinicopathologic features of fifteen myelolipomatous adrenal adenomas, the largest series published thus far.

Sarcomatoid Mesothelioma: A Clinicopathological and Immunohistochemical Study of 64 Cases.

Sixty-four cases of sarcomatoid pleural mesothelioma represent the basis of this study. The patients are 51 men and 13 women between the ages of 42 and 79 years, who presented with symptoms of chest pain, cough, and weight loss. Diagnostic imaging showed the presence of diffuse pleural thickening with encasement of the lung parenchyma in all the cases. All patients had surgical resection via extrapleural pneumonectomy. By immunohistochemistry, all cases were positive for cytokeratin AE1/AE3; however, reactivity with other markers including keratin 5/6, calretinin, and D2-40 was seen in different proportions, whereas a few cases showed positive staining for GATA3, WT1, and p40. All tumors were negative for carcinomatous epitopes (carcinoembryonic antigen, CD15, and TTF1). Our findings show that even though the use of immunohistochemical stains plays an important role in the final interpretation, the best results are accomplished by a global interpretation of clinical, radiographical, and immunohistochemical findings. It is also important to highlight that it does not seem to be a single immunohistochemical stain that is pathognomonic of sarcomatoid mesothelioma and that some other stains that are commonly used for other tumors may also show positive staining in a small percentage of sarcomatoid mesotheliomas.

Primary Giant Cell Tumors of the Lung: A Clinicopathologic and Immunohistochemical Study of 3 Cases.

Three cases of primary giant cell tumors of the lung akin to those described in the soft tissues are presented. The patients are 3 men between the ages of 43 and 54 years who presented with nonspecific symptoms of cough, chest pain, and shortness of breath. None of the patients had any prior history of malignancy anywhere else. Diagnostic imaging disclosed the presence of an intrapulmonary mass. All the patients underwent lobectomy. Grossly, the tumors were described as solid, slightly hemorrhagic, and measuring between 1.8 and 2.4 cm in greatest diameter. Histologically, the tumors were characterized by a dual population of multinucleated giant cells admixed with a mononuclear proliferation. Nuclear atypia was mild to moderate, and mitotic activity varied but was under 5 mitotic figures per 10 high power fields. Immunohistochemical stains showed positive staining for vimentin, CD68, and cathepsin K, whereas the tumors were negative for keratin, TTF-1, p40, S-100 protein, and SABT-2. Clinical follow-up was obtained in 2 patients who have remained alive and without evidence of recurrence or metastasis up to 12 months after surgery. One patient was lost to follow-up. The current neoplasms represent a tumor that to the best of our knowledge has not been reported as a primary neoplasm of the lung. The cases herein described represent an unusual occurrence and should be maintained in the differential diagnosis of primary pulmonary tumors rich in multinucleated giant cells.

Primary pulmonary hyalinizing spindle cell tumor with giant rosettes: A clinicopathological and immunohistochemical study of 2 cases.

Two cases of primary intrapulmonary hyalinizing spindle cell tumor with giant rosettes are presented. The patients are one woman and one man ages 37 and 42 years respectively. Both patients presented with non-specific symptoms of cough, dyspnea, and chest pain. Imaging revealed the presence of an intrapulmonary mass. One tumor was located in the left lower lobe while the other tumor was in the right upper lobe. Both patients underwent lobectomy. The tumors ranged from 2.4 to 3.0 cm in greatest dimension and were characterized by the presence of a bland spindle cell proliferation with areas of hyalinization and the presence of the so-called giant rosettes. Immunohistochemical stains were performed and the spindle cell component show positive staining for vimentin and negative staining for Bcl-2, CD34, STAT6, p40. Keratin immunohistochemical stain highlighted the entrapped alveolar epithelium while S-100 protein showed weak focal staining in the spindle cells. Both patients have remained alive and well without evidence of recurrence or metastasis for a period of 6 to 14 months post-surgical resection. The cases herein presented highlight the ubiquitous distribution of this tumor and underscores the importance of keeping this particular tumor in the differential diagnosis of spindle cell tumors of the lung.

Major Pathologic Response in Patients Treated for Non-small Cell Carcinoma of the Lung: Is There a Magic Number in the Histologic Sections to Be Evaluated?

Over the last years, great advancements have taken place in the medical approach to lung non-small cell carcinomas. Currently, with the use of biomarkers and diagnostic molecular pathology, tumors that in the past were treated with conventional chemotherapy, radiation therapy, or both, now similar patients afflicted by non-small cell carcinoma may have other alternative treatments. More importantly, because of those advancements in treatment options, it has become imperative that pathologists not only become familiar with the pathologic response to those treatments but also attempt to provide a pathologic assessment of the different changes that may be present as a result of a particular treatment. Even though for pathologists the demonstration of tumor necrosis and other inflammatory responses because of therapy as well as residual tumor does not represent a difficult task to accomplish, the issue is not in the diagnostic histopathologic assessment but in providing an adequate assessment of tumor viability as well as tumor necrosis and other histopathologic changes. More interesting is to acknowledge that it is in this particular area in which there may be differences in the approach because of the lack of a universal approach regarding how much of a particular tumor needs to be examined. Needless to say, the number of histologic sections examined may at the end be used as a specific parameter for tumor response to a particular treatment. The current review, will highlight, the different methodologies that over the years have been used or employed in the assessment of what is now referred as major pathologic response.

Micronodular Thymomas With Prominent Cystic Changes: A Clinicopathological and Immunohistochemical Study of 25 Cases.

Twenty-five cases of micronodular thymomas with prominent cystic changes are presented. The patients are 13 men and 12 women between the ages of 38 and 69 years. Clinically, the majority of patients presented with nonspecific symptoms of cough, chest pain, and dyspnea. Four patients were asymptomatic. Diagnostic imaging showed the presence of an anterior mediastinal mass and surgical resection of the tumor mass was performed in all the patients. Histologically, all the tumors were characterized by the presence of cystic structures of varying sizes lined by different types of epithelium. In addition, the tumors were characterized by nodules of epithelial cells embedded in a lymphocyte-rich stroma with germinal centers. Twenty-one tumors were encapsulated while 4 tumors were minimally invasive. Immunohistochemical stains were positive for keratin in the nodular epithelial component while CD45 and CD20 were positive in the lymphoid component. Clinical follow-up ranging from 12 to 24 months was obtained in 19 patients. All the patients were alive and well without disease. No clinical follow-up was available in 6 patients. The cases presented in this article highlight the existence of cystic micronodular thymomas, which can be easily misdiagnosed as a multilocular thymic cyst.

Sinonasal analogue HPV related breast multiphenotypic carcinoma, a report of a case with the first description in the breast.

BACKGROUND: High grade basal-like breast carcinomas are triple negative, express basal cytokeratins, and are known for the overall poor prognosis and aggressive behavior. HPV related multiphenotypic sino-nasal carcinoma has overlapping histology with basal-like breast carcinomas, but carry the defining feature of association with high risk HPV. CASE PRESENTATION: We present a case of a perimenopausal woman with a non-healing ulcerated lesion involving the nipple and breast following a trauma. Biopsy performed showed an HPV-positive basal-like carcinoma with squamous differentiation involving the breast, analogous to multiphenotypic carcinoma previously described in the sinonasal tract. CONCLUSION: This is the first report of a case of a high- risk HPV related basal-like carcinoma with squamous differentiation, described in the literature. We highlight the morphology and immunophenotype of this lesion and its recognition when compared to other multiphenotypic lesions of the breast, and suggest that pathologists should consider HPV evaluation when encountering similar basal-like tumors involving the breast.

Primary Liver Diffuse Large B-Cell Lymphoma following Complete Response for Hepatitis C Infection after Direct Antiviral Therapy.

INTRODUCTION: Hepatitis C infection is highly prevalent worldwide and has a well-known association with B-cell lymphoid malignancies. Antiviral therapy has successfully decreased the rate of liver cirrhosis and improved the outcome in patients with hepatitis C-associated lymphomas. However, although there are a few case reports of aggressive lymphomas after successful hepatitis C therapy, the mechanism behind this association remains unclear. CASE PRESENTATION: We present the case of a 55-year-old man with chronic hepatitis C infection and liver cirrhosis who received antiviral therapy with sofosbuvir and ribavirin and achieved a sustained complete virological response. One year after successful therapy, there was an unexplained decline of his liver function and atypical liver nodularity, which led to the diagnosis of a primary liver diffuse large B-cell lymphoma. DISCUSSION: We review the evidence supporting possible mechanisms of lymphomagenesis after successful hepatitis C therapy, particularly involving late "second-hit" mutations after viral-induced DNA damage and antiviral therapy facilitating the emergence of latent malignant B-cell clones by decreasing local inflammation and immune surveillance. More reports may help elucidate any association between hepatitis C antiviral therapy and late lymphoid malignancies.

Validation of a Patient-Completed Caprini Risk Assessment Tool for Spanish, Arabic, and Polish Speakers.

Targeted prophylaxis for venous thromboembolism (VTE) using the Caprini risk score (CRS) is effective reducing postoperative VTE. Despite its availability as preventive strategy, risk scoring remains underutilized. Critics to the CRS contend the time it takes to complete, and its limitation to English language. Aim is to create and validate patient-completed CRS tools for Spanish, Arabic, and Polish speakers. We translated the first patient-completed CRS to Spanish, Arabic, and Polish. We conducted a pilot study followed by the validation study. Using PASS version 11, we determined that a sample size of 37 achieved a power of 80%, to detect a difference of 0.1 between the null hypothesis correlation of 0.5 and the alternative hypothesis correlation of 0.7 using a 2-sided hypothesis test, significance level of .05. We tabulated and categorized scores using SPSS version 23 to estimate κ, linear correlation, and Bland Altman test. κ value >0.8 was defined as "almost perfect agreement." From 129 recruited patients, 50 (39%) spoke Spanish, 40 (31%) spoke Arabic, and 39 (30%) spoke Polish; average age 51 (16.69) years, 58 (45%) were men, with less than college education (67%). Mean (standard deviation) CRS was 5 (3.90), the majority (63%) above moderate VTE risk. We report excellent agreement comparing physician and patient results (κ = 0.93) and high correlation 0.97 ( P < .01) for the overall score. Bland Altman did not show trend for extreme values. We created and validated the first Spanish, Arabic, and Polish versions of the patient-completed CRS, with excellent correlation and agreement when compared to CRS-trained physician-completed form. Based on these results, the physician needs to calculate the body mass index. Completing the form was not time-consuming.

A Case Report of Parvovirus B19 Infection in a Renal Allograft.

Parvovirus B19 infection is undiagnosed in recipients undergoing solid organ transplantation. It is usually responsible for unexplained acute and chronic red blood cell aplasia that does not respond to erythropoietin therapy. Cases of parvovirus B19 infection associated with pancytopenia, solid organ dysfunction, and allograft rejection have been described in the literature. The deterioration of the immune system as a result of severe immunotherapy favors the reactivation of a previous infection or the acquisition of a new one. We present a case of a 32-year-old woman with a 1-year history of renal allograft transplant and previous cytomegalovirus (CMV) infection who presented with chest pain, polyarthritis, pancytopenia, and renal dysfunction. A serum sample using polymerase chain reaction showed a parvovirus titer of 13.8 trillion IU/mL and a CMV titer of 800 IU/mL. The renal biopsy revealed nucleomegaly with focal viral inclusions, along with changes associated with immunotherapy toxicity. Electron microscopy demonstrated capillary and tubular epithelial cells with "viral factories," thereby confirming the diagnosis. Thus, screening for parvovirus B19 is advised in high-risk patients who present with refractory anemia to avoid the complications of a chronic infection associated with the fatal rejection of the transplanted organ.