Erdheim-Chester disease of the brain: cytological features and differential diagnosis of a challenging case

Erdheim-Chester disease (ECD) is an uncommon, systemic xanthogranulomatous disorder, with distinct clinicopathological features, that is rarely expected preoperatively. We describe a case that presented in the brain of a 26-yr-old male patient and clinically mimicked the appearance of a neoplasm. The final diagnosis was a surprise. In retrospect, the diagnosis was suggested by the intraoperative "squash" preparations, which demonstrated a mixed cellular proliferation of lymphohistiocytic elements and large, multinucleated cells with vesicular nuclei, prominent nucleoli, and abundant cytoplasm. To the best of our knowledge, this is the first report detailing the cytopathological features of ECD.     

Erdheim–Chester disease with prominent pulmonary involvement associated with eosinophilic granuloma of mandibular bone

We report a patient with eosinophilic granuloma localized to the left mandible who was subsequently shown to have Erdheim–Chester disease involving the lower extremities, omentum and lung. The diagnosis of eosinophilic granuloma was based on the presence of typical CD1a⁺ Langerhans' cell granulomas in a biopsy of mandible. The diagnosis of Erdheim–Chester disease was established on the basis of the pattern of radioisotopic uptake by long bones, seen on a technetium bone scan, and the presence of characteristic histopathological features in biopsies of lung and peritoneum. The pathological findings in lung were compatible with the abnormalities observed by tomodensitometry, but strikingly different from those seen in Langerhans' cell granulomatosis. The differences in the histological features of pulmonary involvement seen in the two diseases, and the possible relationship between Langerhans' cell granulomatosis and Erdheim–Chester disease, are discussed.     

SLE pericardial effusion clinically mimicking hypothyroidism and tuberculosis diagnosed on cytology with LE cells

The occurrence of lupus erythematosus cells (LE cells) in serous body fluids is extremely uncommon but, when present, is highly specific for systemic lupus erythematosus (SLE). LE cells are commonly reported in pleural and peritoneal effusions but very rarely documented in pericardial effusion. Here, we report a case in which pericardial fluid examination clinched the diagnosis of SLE which was clinically suspected of tuberculosis/hypothyroid effusion by striking presence of LE cells on May‐Grünwald Giemsa‐stained and Papanicolaou stained smears. Subsequent serologic studies revealed high titers of anti‐nuclear antibodies and anti‐ds‐DNA confirming the diagnosis of SLE. This case highlights the importance of careful examination of pericardial fluid or pleural or peritoneal fluid in the diagnosis of unsuspected cases of SLE in an era wherein “LE cell detection” is considered to be of historic interest.     

Intraosseous Rosai‐Dorfman disease diagnosed by touch imprint cytology evaluation: A case series

Sinus histiocytosis with massive lymphadenopathy, also known as Rosai‐Dorfman disease (RDD) is a rare benign disorder that primarily affects the lymph nodes. Localized lymphadenopathy is the most common clinical manifestation of this disorder. However, RDD has been described in several extra‐nodal sites including the head and neck region, soft tissue, skin, upper respiratory tract, gastro‐intestinal tract and central nervous system (CNS). Involvement of the bone is considered very rare, occurring in less than 10% patients. RDD is one of the histiocytoses and the differential diagnosis includes entities such as Langerhans cell histiocytosis and Erdheim‐Chester disease. In the rare intraosseous variant, the clinical and radiologic differential diagnosis is broader and includes neoplasms such as osteosarcoma and Ewing sarcoma. In this report, we describe three cases of extra‐nodal, intraosseous RDD where touch imprint cytology played a crucial role in diagnosis. Two of the cases initially presented with involvement of the head and neck region and later developed intraosseous disease; while the third patient presented with primary bone involvement. The diagnosis was established by core biopsy with touch imprints of the bone lesions. The cytologic samples showed numerous histiocytes, often with neutrophils within their cytoplasm (emperipolesis) in addition to lymphocytes and plasma cells. The diagnosis of RDD was confirmed with appropriate immunohistochemical stains. Our account of these three cases of intraosseous Rosai‐Dorfman disease highlights the role of cytology in the diagnosis of this rare entity.     

IgG4‐related disease of the paratestis with the scrotal fluid: A case report

IgG4‐related disease (IgG4‐RD) can affect various organs, and the pancreas and salivary gland are representative examples. We report a rare case of IgG4‐RD of the paratestis. A 74‐year‐old man presented with left scrotal swelling. Scrotopuncture drainage and cytology confirmed a clear, yellow retention liquid (130 mL) with many small, similar lymphocytes and a few plasmacytes. Many lymphoid cells were immunopositive for CD3 on a cell block section, indicating that a predominant type of lymphoid cells was T cell. There were also some CD20 immunopositive cells and a few IgG4 immunopositive cells. Two months later the left scrotal swelling had returned, and he underwent radical inguinal orchiectomy. Microscopically, there was considerable lymphoplasmacytic inflammatory infiltration, fibrosis and abundant IgG4 immunopositive cells in the paratesticular region. The histopathologic and immunohistochemistry findings were consistent with IgG4‐RD. However, the abundant T cells in the scrotal fluid complicated the cytological diagnosis in our case.     

Fine-needle aspiration cytology of Castleman disease: case report with review of the literature

Organs involved by Castleman disease (CD) may be investigated by fine-needle aspiration cytology. No specific cytomorphological criteria are currently described for a definitive diagnosis. The cytological features of three fine-needle aspirations from three different lymph nodes of a patient with histologically confirmed CD of the hyaline-vascular type are herein reported, with a review of the literature. The fine-needle aspirations showed branching capillaries associated with fragments of germinal center. Review of the literature yielded 12 other case reports with over half describing similar findings. Because branching hyalinized small blood vessels penetrating follicular germinal center are characteristic of CD of the hyaline-vascular type on histology, this finding in fine-needle aspirates should raise that diagnostic possibility.     

Tumoral calcium pyrophosphate dihydrate crystal deposition disease: A rare diagnosis by fine‐needle aspiration

Calcium pyrophosphate dihydrate crystal deposition disease (CPPD) is a well‐recognized inflammatory joint disorder characterized by presence of calcium pyrophosphate dihydrate crystals in intraarticular and periarticular tissue. We report here a case of a 48‐year‐old male who presented with painless right hand swelling. Clinical suspicion was that of malignant soft tissue tumor. Fine‐needle aspiration (FNA) yielded chalky white gritty material. Microscopic examination showed large areas of basophilic calcified material, histiocytes, giant cells and characteristic rhomboid shaped crystals. At places, chondroid material was also identified, hence, diagnosis of CPPD was made. This was confirmed on histopathological examination. Tophaceous/ tumoral pseudogout is a rare form of CPPD and it is important to recognize that this form can be diagnosed in FNA cytology (FNAC) and misdiagnosis of benign or malignant cartilaginous lesions can be avoided. Diagn. Cytopathol. 2010. © 2009 Wiley‐Liss, Inc.     

Kikuchi‐fujimoto disease in fine‐needle aspiration smears: A clinico‐cytologic study of 76 cases of KFD and 684 cases of reactive hyperplasia of the lymph node

Kikuchi‐Fujimoto disease (KFD) is cytologically characterized by a polymorphous lymphoid cell population, abundant karyorrhectic debris and histiocytes, many of which are crescentic (Kikuchi histiocytes). As per reviewed literature, KFD may be confused with tuberculosis, lymphoma, and reactive hyperplasia of lymph nodes (RHLN). Since RHLN was found to be a major challenging factor during routine cytodiagnosis of KFD in our material, we tried to find out the differentiating clinico‐cytologic features between 76 KFD and 684 RHLN cases seen in Kuwait. 63.2% of KFD were in 3rd and 4th decades of life as compared to 40.2% of RHLN (P = 0.0002). Male to female ratio was 1: 2.45 for KFD and 1:1.09 for RHLN (P = 0.0022). Kuwaiti:non‐Kuwaiti ratio was 1:2.04 for KFD and 1.31:1 for RHLN (P < 0.0001). Capillary networks was present in 71.1% of KFD smears and 52.6% of RHLN (P = 0.0023). Tingible body macrophages and dendritic reticulum cells were detected in 17.1% and 22.4%, respectively, in KFD as opposed to 50.1% and 58.8%, respectively, in RHLN (P < 0.0001). Kikuchi histiocyte count ranged from 2 to 36% in KFD and was ≥10% in 31 (40.8%). Rare Kikuchi histiocytes were detected in 16 (2.3%) of RHLN cases but in none of them the count exceeded 1%, whereas their count was >1% in all KFD cases (P < 0.0001). Thus, KFD cases differed significantly from RHLN in respect of age and sex distribution, Kuwaiti:non‐Kuwaiti ratio, and cytomorphologic features such as capillary networks, Kikuchi histiocyte count, dendritic reticulum cells, and tingible body macrophages. Diagn. Cytopathol. 2013;41:288–295. © 2011 Wiley Periodicals, Inc.     

Replication study of genome‐wide associated SNPs with late‐onset Alzheimer's disease

Late‐onset Alzheimer's disease (LOAD) is a multifactorial disease with the potential involvement of multiple genes. Four recent genome‐wide association studies (GWAS) have found variants showing significant association with LOAD on chromosomes 6, 10, 11, 12, 14, 18, 19, and on the X chromosome. We examined a total of 12 significant SNPs from these studies to determine if the results could be replicated in an independent large case–control sample. We genotyped these 12 SNPs as well the E2/E3/E4 APOE polymorphisms in up to 993 Caucasian Americans with LOAD and up to 976 age‐matched healthy Caucasian Americans. We found no statistically significant associations between the 12 SNPs and the risk of AD. Stratification by APOE*4 carrier status also failed to reveal statistically significant associations. Additional analyses were performed to examine potential associations between the 12 SNPs and age‐at‐onset (AAO) and disease duration among AD cases. Significant associations were observed between AAO and ZNF224/rs3746319 (P = 0.002) and KCNMA1/rs16934131 (P = 0.0066). KCNMA1/rs16934131 also demonstrated statistically significant association with disease duration (P = 0.0002). Although we have been unable to replicate the reported GWAS association with AD risk in our sample, we have identified two new associations with AAO and disease duration that need to be confirmed in additional studies. © 2011 Wiley‐Liss, Inc.     

Metastatic squamous-cell carcinoma in pericardial effusion: Report of four cases,two with cardiac tamponade

For reasons unknown, metastatic squamous-cell carcinoma is a rare cause of pleural effusions and is even less common in pericardial effusions. A review of all pericardial effusions examined in the Cytology Service at Montefiore Medical Center over a 15-year (1980–1994) period was undertaken (N = 251). Four cases with metastatic squamous-cell carcinoma were identified among 39 malignant effusions. Two patients with metastatic squamous-cell carcinoma presented with cardiac tamponade, and the other two cases had progressive cardiac failure. The diagnostic cells on cytology evaluation were scant in all four cases but exhibited classical features of metastatic squamous carcinoma, such as cytoplasmic keratinization, intercellular bridges, and occasional “pearl” formation. Pericardial biopsies available in three patients, two with cardiac failure and one with cardiac tamponade, were negative. In all four cases the primary tumor was a bronchogenic carcinoma. Metastatic squamous-cell carcinoma is an uncommon cause of pericardial effusion and usually indicates the presence of a bronchogenic carcinoma with a rapidly fatal outcome. Cytologic examination of pericardial fluid is essential in the evaluation of such patients. Diagn. Cytopathol. 1998;18:422–424. © 1998 Wiley-Liss, Inc.     

Cytological features of lung adenocarcinoma with micropapillary pattern in the pleural or pericardial effusion: analysis of 5 cases

Micropapillary pattern is a distinct histopathological pattern, and usually shows a high frequency of lymphatic invasion and lymph node metastases. This pattern is also reported in lung adenocarcinoma, however, only one cytological report of lung adenocarcinoma with micropapillary pattern has been reported. In this study, we analyzed the cytological features of this type of carcinoma in the pleural or pericardial effusion. This study was comprised of 5 consecutive cases of lung adenocarcinoma with micropapillary pattern, in which the tumor cells were present in the pleural or pericardial effusion and whose diagnoses were histopathologically confirmed. The characteristic cytological findings in the pleural or pericardial effusion were as follows: i) tightly cohesive small nests of tumor cells showing papillary structure without fibrovascular core, ii) these nests were comprised of approximately 5-20 tumor cells, iii) cauliflower-like and acinar-like structures were also observed, iv) intracytoplasmic vacuoles were observed in 40% of the cases, and v) the neoplastic cells had large round to oval nuclei containing coarse chromatin and occasional conspicuous nucleoli. It has been reported that the presence of micropapillary structure and intracytoplasmic vacuolation are also characteristic cytological features of micropapillary carcinoma of the urinary bladder, therefore, they are thought to be common cytological features of carcinomas with micropapillary pattern. Consequently, detection of these features can lead to a cytodiagnosis of lung adenocarcinoma with micropapillary pattern in the pleural or pericardial effusion. Recognition of these features is important because this type of tumor shows an aggressive clinical course.     

Donor and host B cell‐derived IL‐10 contributes to suppression of graft‐versus‐host disease

Graft‐versus‐host disease (GvHD) is a frequent life‐threatening complication following allogeneic HSC transplantation (HSCT). IL‐10 is a regulatory cytokine with important roles during GvHD, yet its relevant sources, and mode of action, remain incompletely defined in this disease. Using IL‐10‐deficient donor or host mice (BALB/c or C57BL/6, respectively) in a MHC‐mismatched model for acute GvHD, we found a strongly aggravated course of the disease with increased mortality when either donor or host cells could not produce this cytokine. A lack of IL‐10 resulted in increased allogeneic T‐cell responses and enhanced activation of host DCs in spleen and MLNs. Remarkably, IL‐10 was prominently produced by host‐ and donor‐derived CD5^intCD1d^intTIM‐1^int B cells in this disease, and consistent with this, allogeneic HSCT resulted in exacerbated GvHD when mice lacking IL‐10 expression in B cells were used as donor or host, compared with controls. Taken together, this study demonstrates that host and donor B cell‐derived IL‐10 provides a unique mechanism of suppression of acute GvHD, and suggests that DCs are the targets of this B cell‐mediated suppressive effect. These findings open novel therapeutic possibilities based on the use of B cells to increase the feasibility of allogeneic HSCT.