Morphological and immunohistochemical characteristics associated with metastatic and recurrent progression in pheochromocytoma/paraganglioma: A cohort study.

This study aimed to evaluate immunohistochemical markers of pheochromocytoma/paraganglioma (PPGL) and the relationships between the grading system for adrenal pheochromocytoma and paraganglioma (GAPP) and the prognosis of PPGL in a Chinese population. A retrospective analysis was conducted on a cohort of 102 PPGL cases, from January 2012 to December 2019, with complete clinicopathological and follow-up data. Surgical pathology slides were re-reviewed. All histological parameters involved in GAPP were summarized. The relationship between clinical characteristics, expression of SDHB (succinate dehydrogenase), S-100 and Ki-67 as well as GAPP classifications and prognosis of PPGL was statistically analyzed. The 102 cases included 51 males (50%) and 51 females (50%) with a median age of 48.7 years. The median tumor size was 6.8 cm. Metastases or relapse developed in 23 (22.5%) cases. Larger tumor size, extra-adrenal location, and poorly differentiated PPGL according to GAPP were associated with metastases or relapse (P < 0.05). Histological parameters, including the appearance of large or fused cell nests, necrosis, vascular invasion, and capsular invasion, were more common in the cases with metastases or relapse (P < 0.01). Loss of SDHB or S-100 expression was more common in poorly differentiated PPGL and associated with metastases or relapse (P < 0.01). However, no significant difference in the Ki-67 index between the clinically malignant and benign group was observed. GAPP is thus helpful for evaluations of the biological behavior of PPGL.

Aberrant phenotypes in Kikuchi's disease.

Initial reports emphasized the immunophenotypic similarities between benign and malignant T cell populations, while some previous studies indicating that aberrant T-cell antigen loss is a good marker for detecting malignant T-cell proliferation. Recently, we found a very interesting and thought-provoking phenomenon: In benign disease-28 of 38 (73.7%) cases of Kikuchi's disease also showed aberrant phenotypes with loss of pan-T cell antigens, which makes the differential diagnosis between Kikuchi's disease and T cell lymphoma more challenging. In our study, 38 cases of Kikuchi's disease and 30 cases of reactive lymphoid hyperplasia (RLH) were studied by EliVision immunohistochemical staining. As well as TCR gene rearrangement using PCR was negative in 10 tested cases of the Kikuchi's disease. Among these cases, the most common antigen deficiency was CD5 (22 cases), then CD7 (11 cases), CD2 (8 cases) and CD3 (2 cases). Compared with proliferative and xanthomatous types of Kikuchi's disease, antigens tended to be lost in necrotizing type. Based on follow-up data, a correlation was not found between the occurrence of aberrant phenotypes and prognosis. In RLH, obvious pan-T cell antigen loss was also not found. In conclusion, this is the first study to demonstrate distinct patterns of antigen loss in Kikuchi's disease, suggesting that T cell antigen loss is not reliable as an auxiliary diagnostic standard for T cell lymphoma.

[Clinicopathologic analysis of intestinal follicular lymphoma first presenting with gastrointestinal symptoms].

OBJECTIVE: To study the clinical features, endoscopic findings, pathologic diagnosis and treatment options of intestinal follicular lymphoma first presenting with gastrointestinal symptoms. METHODS: The clinical features, pathologic findings and follow-up data were retrospectively studied in 9 cases of intestinal follicular lymphoma. Immunohistochemical study for CD3, CD5, CD20, CD21, Ki-67, bcl-2, bcl-6, CD10 and cyclin D1 was carried out. RESULTS: Seven of the 9 patients were females and two were males. The age of patients ranged from 5 to 60 years (mean = 44 years). The clinical manifestations included abdominal pain (5 cases), blood in stool (3 cases) and abdominal distension (1 case). The commonest site of involvement was ileocecal region (6/9). Endoscopic examination had been carried out in 6 patients and all showed the presence of multiple polyps. Five cases had undergone endoscopic biopsy. Histologic examination of the endoscopic biopsies showed lymphoma cells located mainly in mucosal layer, forming vague nodules with ill-defined boundaries. Plasma cells and eosinophils were not conspicuous. Immunohistochemically, the tumor cells in all cases diffusely expressed CD20, CD10 and bcl-2. The staining for CD3, CD5 and cyclin D1 was negative. Lymphoid cells with weak CD10-positivity were identified in the interfollicular regions. Four cases were treated with surgical resection and chemotherapy. The other 3 cases received chemotherapy only and the remaining cases were treated conservatively. All of them were still alive on follow up. CONCLUSIONS: Primary intestinal follicular lymphoma affects predominantly elderly patients and has a female predilection. The commonest site of involvement is ileocecal region. Endoscopic examination shows polypoid changes. The disease often runs a relatively indolent clinical course. The prognosis is better than that of primary nodal follicular lymphoma.

[Langerhans cell sarcoma: a case report and literature review].

OBJECTIVE: To explorer the clinical features, diagnosis and therapy of Langerhans cell sarcoma (LCS). METHODS: The clinical data of a case of LCS originated from cervical lymph nodes was analyzed. The pathological biopsy was studied by cell morphology, immunohistochemistry and electron microscopy, and the related literature was reviewed. RESULTS: The giant tumor cells were characterized by markedly malignant proliferation, irregular nuclei and obviously chromatin abnormality, the positive S-100, CD1a and Langerin (CD207) tumor cells were revealed by immunohistochemistry, and Birbeck granules could be found by electron microscopy. All of them supported the diagnosis of LCS. The patient's condition progressed rapidly and died of multiple organ failure in a short time. CONCLUSION: LCS is an extremely rare neoplastic proliferation of Langerhans cells with overtly malignant cytologic features and spreads aggressively. The diagnosis of LCS mainly relies on pathological cell morphology, immunohistochemistry and electron microscopy if necessary. The treatment includes chemotherapy, surgery and radiotherapy, etc, but lack of generally accepted optimal treatment regimen currently. In short, LCS has intensive invasiveness and poor prognosis.

[Clinicopathologic features of systemic EBV-positive T/NK-cell lymphoproliferative disease in adults].

OBJECTIVE: To study the clinicopathologic features, immunophenotype, clonality and Epstein-Barr virus (EBV) status of systemic EBV-positive T/NK-cell lymphoproliferative disease in adults (ASEBV(+)T/NK-LPD). METHODS: Twenty cases of ASEBV(+)T/NK-LPD were analyzed retrospectively with histopathologic review, immunohistochemistry and in-situ hybridization for EBV-encoded RNA (EBER). The follow-up data were collected. RESULTS: There were altogether 15 males and 5 females. The median age of the patients was 34 years. The average duration from onset of symptoms to diagnosis was 8.7 months. Fever (18/20), hepatosplenomegaly (18/20) and lymphadenopathy (17/20) were the main clinical manifestations. Eleven of the 17 patients died during follow-up, with a mean survival of 2.9 months. Histologically, there was obvious expansion of T zone of the involved lymph nodes, associated with diminished lymphoid follicles. The interfollicular areas were widened and infiltrated by small to median-sized lymphoid cells which showed only mild atypia. Scattered large lymphoid cells were not uncommon. The nodal capsule was thickened in 6 cases. Focal necrosis was seen in 9 cases. Sinus histiocytic proliferation with erythrophagocytosis was observed in 3 cases. In addition, there were mild atypical lymphoid cells infiltrate into the liver, spleen, intestinal mucosa and bone marrow. Immunohistochemical study and in-situ hybridization showed that the EBER-positive cells were of T-cell lineage, with CD3 expression. They were also positive for cytotoxic molecules (granzyme B or TIA-1). Only 1 case was CD56 positive. A predominance of CD8-positive cells was demonstrated in 8 of the 14 cases studied, while CD4-positive cells predominated in the remaining 5 cases. One case showed similar proportion of CD8 and CD4-positive cells. The number of EBER-positive cells ranged from 30 to more than 300 per high-power fields. These EBER-positive cells were of small to large size and located mainly in the expanded T zone and occasionally in the germinal centers. Three of the 7 cases exhibited clonal rearrangement of T-cell receptor gamma gene, while the other 4 cases exhibited polyclonal rearrangement of T-cell receptor gamma gene. CONCLUSIONS: ASEBV(+)T/NK-LPD is a systemic disease with a subacute or chronic clinical course. Most patients suffer from relapsing fever, lymphadenopathy and hepatosplenomegaly. The disease is characterized by proliferation of EBV-infected cytotoxic T cells. The T zone of the involved lymph nodes shows expansion by mildly atypical lymphoid cells. The disease is associated with poor clinical outcome and can be life-threatening. The patients often die of multiorgan failure and bleeding.

[Loss of pan-T cell antigens CD2, CD3, CD5 and CD7 in Kikuchi's disease].

OBJECTIVE: To study the possible loss of pan-T cell antigens CD2, CD3, CD5 and CD7 in Kikuchi's disease and to evaluate the role of T cell antigen loss in distinguishing benign from malignant T-cell lymphoid lesions. METHODS: Formalin-fixed and paraffin-embedded tissues of 33 cases of Kikuchi's disease and 15 cases of reactive lymphoid hyperplasia were studied by EliVision immunohistochemical staining for CD2, CD3, CD5 and CD7. RESULTS: Twenty-four of the 33 (72.7%) cases of Kikuchi's disease lost one or more of the pan-T cell antigens, including the loss of CD5 only (13 cases), CD7 only (1 case), CD2 only (1 case), CD2 and CD7 (2 cases), CD5 and CD7 (4 cases), CD2 and CD5 (2 cases), and CD2, CD7 and CD5 (1 case). Amongst these cases, the commonest antigen loss was CD5 (20 cases, 60.6%), followed by CD7 (8 cases, 24.2%) and CD2 (6 cases, 18.2%). Compared with the xanthomatous subtype of Kikuchi's disease, the loss of antigens was more commonly seen in the proliferative and necrotizing subtypes. Analysis of follow-up data showed that the loss of antigens in Kikuchi's disease was not significantly associated with the prognosis. In reactive lymphoid hyperplasia, the expression of CD2, CD3, CD5 and CD7 was seen in all cases with similar intensity, with no obvious pan-T cell antigen loss. CONCLUSION: Loss of one or more pan-T cell antigens in Kikuchi's disease is demonstrated in present study, suggesting that the immunophenotypic pattern is not unique in T cell lymphoma.

[Intralymphatic accumulation of lymphocytes mimicking intravascular lymphomatosis].

OBJECTIVE: To study the significance and differential diagnosis of intralymphatic accumulation of lymphocytes. METHODS: The clinical and pathologic features of 4 cases of intralymphatic accumulation of lymphocytes were reviewed retrospectively. Immunohistochemical study was carried out and follow-up data were analyzed. RESULTS: The sites of involvement included tonsil (2 cases), pharynx (1 case) and appendix (1 case). The duration of disease ranged from 1 week to 3 months. Follow up of the patients (from 3 to 84 months) showed no evidence of disease recurrence. Gross examination of the tissues (except in the case of appendiceal involvement) showed polypoid changes. Histologically, the lymphatic channels were filled up with small lymphocytes and associated with fibrosis in the vicinity. Immunohistochemical study revealed a T-cell phenotype of the intralymphatic lymphoid cells. CONCLUSIONS: The accumulation of lymphocytes in lymphatic channels is associated with a benign clinical course. This phenomenon may be due to retention of lymphocytes secondary to the perilymphatic chronic inflammation and fibrosis. Although the lesion simulates intravascular lymphomatosis morphologically and shows a uniform T-cell phenotype, the lymphoid cells lack obvious cellular pleomorphism and mitotic activity. The solitary nature of the lesion, when coupled with the indolent clinical behavior, is also helpful in the differential diagnosis.