PU.1 is a useful nuclear marker to distinguish between histiocytosis and histiocyte-rich tumours.

AIMS: The aim was to test the expression of PU.1 on different types of histiocytoses and to test the utility of PU.1 in confirming or excluding a histiocytic origin in tumour samples with suspicion of histiocytosis. METHODS AND RESULTS: We analysed 66 biopsies of nonmalignant histiocytoses represented by Langerhans-cell histiocytosis (n = 13), Erdheim-Chester disease (ECD) (n = 19), Rosai-Dorfman disease (RDD) (n = 14), mixed ECD-RDD (n = 3), ALK-positive histiocytosis (n = 6), and juvenile xanthogranuloma (n = 11). All cases were positive for PU.1 in reactive and neoplastic histiocytes. In addition, 39 cases of tumours with high-grade cytological atypia were referred to our center as suspicion of malignant histiocytosis/histiocytic sarcoma and only 18 were confirmed. Indeed, more than half of these tumours (21/39) were either undifferentiated malignant tumours with a stroma rich in histiocytes, diffuse large B-cell lymphoma, or high-grade dedifferentiated liposarcoma. PU.1 was useful to distinguish between the negativity of large atypical nuclei and the positivity of stromal reactive histiocytes. CONCLUSION: PU.1 is expressed by all types of histiocytosis. It distinguishes histiocytosis from histiocyte-rich tumours with an easy interpretation due to its sharp nuclear staining. Its negativity in lesional/tumour cells in histiocyte-like lesions is useful to eliminate a histiocytosis.

[Myoepithelial tumors of soft tissue: A case of mixed tumor]. / Tumeurs myoépithéliales des tissus mous : à propos d'un cas de tumeur mixte.

Myoepithelial neoplasms of soft tissue represent a rare entity which has been described only recently when compared to salivary gland tumors with whom they share histopathological and molecular features. The most common locations are the superficial soft tissues of the limbs and limb girdles. However, they can rarely occur in the mediastinum, abdomen, bone, skin and visceral organs. Benign forms (myoepithelioma and mixed tumor) are more frequent than myoepithelial carcinoma and the latter mostly affects children and young adults. Diagnosis is mainly based on histology, which shows a proliferation of myoepithelial cells of variable morphology with or without glandular structures in a myxoid background, and immunohistochemistry, which shows co-expression of epithelial and myoepithelial markers. Molecular tests are not mandatory, but in selected cases FISH analysis can prove useful as about 50% of myoepitheliomas show EWSR1 (or rarely FUS) rearrangements and mixed tumors show PLAG1 rearrangements. Here, we present a case of a mixed tumor of the soft tissue occuring in the hand with expression of PLAG1 in immunohistochemistry.

OCT2 expression in histiocytoses.

Diagnosis of histiocytosis can be difficult and one of the biggest challenges is to distinguish between reactive and neoplastic histiocytes on histology alone. Recently, OCT2 nuclear expression was reported in Rosai-Dorfman disease (RDD). Our purpose was to expand the testing of OCT2 on a broader variety of sporadic or H syndrome-related histiocytoses. Cases of histiocytoses were retrieved from the files of Ambroise Paré Pathology Department. All slides and molecular analyses were reviewed, and staining was completed with immunohistochemistry for OCT2. A total of 156 samples from different localizations were tested. Among sporadic cases, 52 patients had RDD, and 10 patients had mixed histiocytosis combining RDD with Erdheim Chester disease (ECD, n = 8), Langerhans cell histiocytosis (LCH, n = 2) or juvenile xanthogranuloma (JXG, n = 1). All these patients were positive for OCT2 in RDD characteristic histiocytes. Twenty-three patients had ECD and all but two (91% - 21/23) were negative for OCT2. By contrast, OCT2 was positive in 11/27 (41%) LCH and 6/16 (38%) JXG. Among the 10 samples of H syndrome-associated histiocytosis, 3 had typical RDD histology, 6 had unclassified histiocytosis, and one had mixed RDD-LCH; all were positive for OCT2. On 16 samples of granulomatous lymphadenitis, OCT2 was negative in epithelioid histiocytes. Our study shows that OCT2 has a sensitivity of 100% for RDD cases and mixed histiocytoses with an RDD component. It is negative in 92% of ECD but expressed in at least 38% of LCH, JXG, and C group histiocytoses. Finally, OCT2 is positive in all H syndrome-related histiocytoses, independent of their histology.

Granulomatous splenic mass with necrosis revealing an EBV-positive inflammatory follicular dendritic cell sarcoma.

Epstein-Barr virus-positive inflammatory follicular dendritic cell sarcoma is a variant of follicular dendritic cell neoplasm most often arising in the liver or spleen. Two histological patterns can be identified in this variant, namely a granulomatous and an eosinophil-rich one. We present the case of a 69-year-old woman with a splenic mass. After being removed, the mass was gray-whitish with an area of necrosis. Histology showed a diffuse distribution of epithelioid granulomas in a background of a dense lymphoplasmacytic infiltrate. Rare atypical cells EBV+ and CD21+ were present in the intergranulomatous areas. Differential diagnosis for the granulomatous type EBV+ inflammatory follicular dendritic cell sarcoma includes infection, sarcoidosis, inflammatory myofibroblastic tumor, T cell lymphoma and vasculitis. The origin of this neoplasm is the follicular dendritic cell, and, due to its similarities with a myofibroblast, differential diagnosis can be challenging. Immunohistochemistry for dendritic markers and in situ hybridization for EBER remain diagnostic keys.

Peritoneal or mesenteric tumours revealing histiocytosis.

OBJECTIVE: Peritoneal or mesenteric tumours may correspond to several tumour types or tumour-like conditions, some of them being represented by histiocytosis. This rare condition often poses diagnostic difficulties that can lead to important time delay in targeted therapies. Our aim was to describe main features of histiocytoses with mesenteric localisation that can improve the diagnostic process. DESIGN: We performed a retrospective study on 22 patients, whose peritoneal/mesenteric biopsies were infiltrated by histiocytes. RESULTS: Abdominal pain was the revealing symptom in 10 cases, and 19 patients underwent surgical biopsies. The diagnosis of histiocytosis was proposed by initial pathologists in 41% of patients. The other initial diagnoses were inflammation (n=7), sclerosing mesenteritis (n=4) and liposarcoma (n=1). The CD163/CD68+CD1a- histiocytes infiltrated subserosa and/or deeper adipose tissues in 16 and 14 cases, respectively. A BRAFV600E mutation was detected within the biopsies in 11 cases, and two others were MAP2K1 mutated. The final diagnosis was histiocytosis in 18 patients, 15 of whom had Erdheim-Chester disease. The median diagnostic delay of histiocytosis was 9 months. Patients treated with BRAF or MEK inhibitors showed a partial response or a stable disease. One patient died soon after surgery, and five died by the progression of the disease. CONCLUSION: Diagnosis of masses arising in the mesentery should be carefully explored as one of the possibilities in histiocytosis. This diagnosis is frequently missed on mesenteric biopsies. Molecular biology for detecting the mutations in BRAF or in genes of the MAP kinase pathway is a critical diagnostic tool.

Paraganglioma presenting as a mesenteric cystic mass: A case report.

The present study aims to raise awareness about the necessity of a thorough differential diagnosis process when diagnosing paraganglioma as it is an extremely rare entity with a high malignant potential. A 64-year-old female patient was admitted to the hospital with symptoms of bowel obstruction and a palpable abdominal mass. Abdominal and pelvic computed tomography revealed a cystic heterogeneously enhanced mass. The tumor was surgically removed and then microscopically analysed. Microscopically, the mass was composed of nests of small polygonal and round cells with central vesicular nuclei, consistent with the diagnosis of mesenteric paraganglioma which was later confirmed by immunohistochemistry. The critical markers for paragangliomas, namely chromogranin A and S100, should be used as the first step in diagnosis, followed by other valuable immunohistochemical markers. A long-term follow-up is extremely important following the diagnosis of paraganglioma as all these tumors have a malignant potential.

A rare case of clear-cell carcinoid of appendix.

The carcinoids are the most frequent type of tumors arising from the appendix. In the majority of cases, these tumors are asymptomatic and usually are discovered after appendectomy. Definitive diagnosis relies on pathological examination of the resected appendix, size of the tumor being critical for the further management. Clear-cell change in neuroendocrine tumors (NETs) has rarely been described in the appendix. We choose to present a clear-cell carcinoid subtype of appendiceal NET to raise awareness on this potentially curable and rare condition that can be overlooked. We highlight the importance of the pathological exam and the morphological and immunohistochemical behavior of the tumor in confirming the diagnosis and aiding in the treatment decision making. Also, important entities should be considered in the process of differential diagnosis such as goblet-cell carcinoid or renal-cell÷ovarian carcinoma.