Myelodysplastic Syndrome Associated with Bone Marrow Fibrosis

Bone marrow biopsy (BMB) in myelodysplastic syndrome (MDS) frequently reveals a slight alteration in the reticulin stroma which does not have any clinical significance. However, in a minority of cases, full-blown bone marrow fibrosis (BMF) can be found.

Primary MDS patients with BMF show distinct clinico-pathological features and an unfavourable prognosis mainly attributable to complications deriving from pancytopenia and continuous transfusions, while leukemic transformation occurs only rarely. Since BMF may characterize other hematological disorders, primary MDS with BMF should be included in the differential diagnosis particularly with malignant myelofibrosis (MM) and idiopathic myelofibrosis (IMF).

Secondary MDS with BMF represent a variety of preleukemic conditions in subjects treated for previous neoplasias. Unlike the primary forms, they do not form a clearcut clinico-pathological entity.     

Surgical implications of hepatic venocclusive disease following bone marrow transplantation

Hepatic venocclusive disease occurs with a spectrum of severity in an estimated 21% of bone marrow transplant patients. Clinical features include severe right upper quadrant pain, ascites, weight gain and initially minimal derangement of liver function. In contrast to hepatic graft versus host disease, venocclusive disease usually occurs within the first three weeks of engraftment and in autologous grafts. Urgent surgical consultation is requested when these features are prominent enough to mimic common acute processes requiring laparotomy. This condition must be included in the differential diagnosis in order to avoid an unnecessary laparotomy in this select group of patients who are usually severely thrombocytopenic and leukopenic. Clinical diagnosis alone is very reliable.     

Bone marrow infiltration as the initial presentation of gastric signet ring cell adenocarcinoma

This case report describes a 52-year-old African American man who initially presented with worsening back pain. The patient was found to have lytic lucencies in the T5 and T9 vertebral bodies and a subsequent bone marrow biopsy revealed an extensive infiltrate of signet ring cells. These findings prompted a workup for a gastrointestinal malignancy, and upper endoscopy revealed a mass in the gastric pylorus. A biopsy of this mass was positive for signet ring cell adenocarcinoma. This case is significant for two reasons. First, it highlights the importance of a broad differential diagnosis when approaching a patient with lytic bone lesions. Second, bone marrow involvement is more common in patients with diffuse type gastric cancer and occurs in particularly young patients. The increasing incidence of diffuse type gastric adenocarcinoma means bone marrow metastases will likely play a greater role in the presentation and management of gastric cancer.     

骨髓涂片、骨髓活检对弥漫性大B细胞淋巴瘤临床分期的价值

目的:探讨骨髓涂片、骨髓活检对弥漫性大B细胞淋巴瘤(DLBCL)临床分期的价值.方法:对44例累及骨髓的病例回顾性分析骨髓涂片及骨髓活检切片,分别比较细胞学形态、组织形态、增生程度、纤维组织增生程度、检出率和敏感性.结果:骨髓涂片中可见中到大型的异型细胞骨髓,切片中瘤细胞以灶型最常见.按Manoharm改良法评估,骨髓切片中网状纤维含量有不同程度增多.骨髓涂片与骨髓切片增生程度的比较,差异有统计学意义(P＜0.05),切片组增生程度高于涂片组.骨髓涂片与骨髓切片检出率的比较,差异有统计学意义(P＜0.05),切片组检出率高于涂片组.骨髓涂片与骨髓切片敏感性的比较,差异有显著统计学意义(P＜0.01),切片组敏感性明显高于涂片组.结论:骨髓涂片简单易行,骨髓切片在骨髓组织状况、优势增生细胞等方面有优势,同时开展涂片和切片的检测,提高检出率,可以修正临床分期,如能同时进行流式细胞免疫表型分析,则更能提高检出率.     

骨髓活检在诊断及鉴别诊断真性红细胞增多症中的价值

目的：探讨骨髓活检在真性红细胞增多症（PV）诊断与鉴别诊断中的价值.方法：同步观察真性红细胞增多症37例患者骨髓涂片和活检切片.并与继发性红细胞增多症20例患者作比较,以正常人20例作对照.观察骨髓增生程度、增生优势细胞系、网硬蛋白积分.结果：PV组患者骨髓造血组织在切片中的增生度明显高于涂片,两者差异有统计学意义（P〈0.05）;与继发性红细胞增多症及正常对照组比较差异亦有统计学意义（P〈0.05）.PV组切片中增生优势细胞系分为累及三系的增生,累及二系（红系和粒系、红系和巨核系）的增生,仅累及红系单系的增生;继发性红细胞增多症组仅显示红系相对增生.PV组网硬蛋白纤维积分为1＋及以上占83.8%,继发性红细胞增多症组及正常对照组均未见1＋或l＋以上,分别比较差异有统计学意义（均为P〈0.05）.结论：骨髓活检能准确反应骨髓组织的增生程度、增生优势细胞系、纤维增生程度,对PV的诊断及鉴别诊断有较高价值.     

胃癌骨髓转移的血液学特征和治疗方式探讨

目的 探讨胃癌骨髓转移患者的临床病理特征、治疗及预后.方法 回顾性分析9例胃癌骨髓转移患者的临床资料,总结其临床特点、诊断和治疗方法.结果 9例患者的年龄为18~68岁,中位年龄为51岁,病理均为低分化腺癌.患者均伴有其他部位转移,常见淋巴结和骨转移.骨痛、非感染性发热、红细胞和血小板二系下降、碱性磷酸酶和(或)乳酸脱氢酶不同程度升高、外周血涂片可见幼稚细胞是胃癌骨髓转移的常见表现.胃癌骨髓转移患者的中位生存期为34 d(11~266 d).结论 胃癌骨髓转移患者的预后差,熟悉胃癌骨髓转移的临床特点有利于早期诊断.     

继发性骨淋巴瘤的18F-FDG PET/CT影像诊断及与骨髓活检诊断效能的比较

目的:分析继发性骨淋巴瘤的PET/CT影像特点,比较骨髓活检（bone marrow biopsy,BMB）及PET/CT诊断骨淋巴瘤各自的优势,探讨如何进一步提高骨淋巴瘤的检出率。方法:回顾性分析放化疗前在我院行PET/CT检查的68例继发性骨淋巴瘤影像及骨髓活检资料。所有病例均病理确诊为淋巴瘤。骨淋巴瘤病灶的诊断标准:BMB阳性或骨局灶性FDG代谢增高且治疗后代谢减低或消失。采用SPSS 16.0统计分析不同分组的SUVmax及诊断效能差异。结果:PET/CT与BMB诊断灵敏度比较:68例中63例行BMB。PET/CT的总体诊断灵敏度及对非惰性淋巴瘤的诊断灵敏度高于BMB（P＜0.05）,而对惰性淋巴瘤,BMB灵敏度略高于PET/CT(P＞0.05)。PET/CT表现与BMB结果:根据PET/CT所见分为骨质破坏组（18例）和骨髓浸润组（50例）,骨质破坏组的SUVmax明显高于骨髓浸润组（P＜0.01）。骨质破坏组以弥漫大B细胞淋巴瘤（diffuse large B cell lymphoma,DLBCL）为主,PET/CT均阳性。骨髓浸润组PET/CT阳性41例,表现为局灶性增高、弥漫不均匀性增高和弥漫均匀性增高,弥漫均匀性增高组的SUVmax明显低于其它两组。BMB阴性21例,其中骨质破坏组8例,局灶性骨髓浸润13例。病理类型与PET/CT表现:31例DLBCL、10例其它侵袭性非霍奇金淋巴瘤（non-Hodgkin's lymphoma,NHL）及6例霍奇金淋巴瘤（Hodgkin's lymphoma,HL）均PET/CT阳性;18例惰性淋巴瘤PET/CT仅11例阳性。DLBCL的SUVmax明显高于惰性淋巴瘤（P＜0.05）。结论:继发性骨淋巴瘤骨髓浸润多于骨质破坏。骨质破坏和局灶性骨髓浸润多见于侵袭性骨淋巴瘤,而弥漫性骨髓浸润更多见于惰性淋巴瘤。PET/CT对骨质破坏、局灶性骨髓浸润的诊断优于BMB,而BMB对弥漫性骨髓浸润的诊断优于PET/CT。联合BMB和PET/CT才能更准确地诊断骨淋巴瘤。     

Immunohistochemical staining of bone marrow biopsies for detection of occult metastasis in breast cancer

Summary Immunohistochemical (IHC) techniques should allow for a greater detection of bone marrow micrometastasis in patients with breast carcinoma. We studied a series of bone marrow (BM) biopsies negative by conventional histologic techniques from 93 patients with breast carcinoma. Prior to this study, twelve BM biopsies, positive by conventional histology, were stained with a panel of monoclonal antibodies (MoAb), directed either against cytokeratin (KL1, AE1-AE3, CAM5-2) or epithelial membrane antigen (EMA, HMFG2). KL1 appeared to be the most sensitive of the markers used in the detection of metastases and is available commercially. It therefore was the only MoAb used with the series of 93 BM biopsies negative by conventional examination. Within this series, among 45 patients clinically suspected of having bone marrow metastasis but with BM biopsies negative by conventional staining, one case showing myelofibrosis stained positive with KL1 demonstrating isolated tumor cells. For the 48 patients without suspicion of bone marrow metastasis at initial diagnosis for breast carcinoma, KL1 revealed no marrow metastasis.Single bone marrow biopsy techniques whether stained by conventional or IHC methods do not appear to be useful tests to detect occult bone marrow metastasis, especially at initial diagnosis of clinically M_o breast carcinoma patients.     

Femoral marrow MRI is a non-invasive,non-irradiated and useful tool for detecting bone marrow involvement in non-Hodgkin lymphoma

Femoral marrow magnetic resonance imaging (MRI) is a non-invasive, non-irradiated and useful modality for evaluating bone marrow (BM) conditions. Human adult femoral BM is almost uniformly fatty marrow and has the largest volume of a single bone. MRI has an extremely high resolution for fat and water, which allows high-contrast imaging of cellular infiltration into fat tissue. In hematological diseases, femoral BM MRI can clearly detect cell infiltration, which is symmetrically imaged from the proximal to the distal direction of abnormal signal areas. Thus, we investigated the significance of femoral MRI for non-Hodgkin lymphoma (NHL). We analyzed the data of 69 NHL patients who received femoral MRI at diagnosis in this single-center retrospective cohort study. The median patient age was 73 years. MRI patterns were mainly classified as uniform patterns or nonuniform patterns. We also classified the range of cellular marrow as high-grade or low-grade based on whether it had spread to over half of the femur. Both overall survival (OS) and progression-free survival (PFS) were significantly influenced by abnormal femoral marrow MRI. In particular, the patients with cellular femoral marrow lesions had a worse OS and PFS based on log-rank tests. Multivariable analyses with the Cox proportional hazards model revealed that OS and PFS were significantly influenced by cellular marrow diagnosed by femoral MRI. We concluded that femoral marrow MRI is a useful tool for detecting BM involvement and an independent prognostic factor in NHL patients.     

Immunophenotype of Bone Marrow Mast Cells in Indolent Systemic Mast Cell Disease in Adults

One of the major advances in the histological diagnosis of bone marrow (BM) involvement in mastocytosis has been the specific immunohistochemical detection of tryptase on most cells (MC), which has shown to be of great diagnostic value, especially in cases of malignant mastocytosis. On the other hand, recent studies have clearly shown that bone marrow mast cells can be specifically identified and accurately enumerated using multiparametric flow cytometry, which allow a systematic analysis of the immunophenotypic characteristics of bone marrow mast cells. Once this flow cytometric approach was applied for the analysis of BMMC from mastocytosis patients clear immunophenotypical differences were found between BMMC from normal individuals and adults with mastocytosis. The most characteristic immunophenotypic feature, both in malignant and adult indolent systemic mast cell disease, being the coexpression of CD2 and CD25 antigens, never present in normal bone marrow mast cells and, which constitute an aberrant hallmark of bone marrow mast cells in adult mastocytosis. Furthermore, bone mast cells from mastocytosis display a higher reactivity for CD35, CD63, and CD69 activation-associated antigens. Based on these results it could be concluded that the use of multiparametric flow cytometric immunophenotyping of BMMC in adult patients suffering from cutaneous mastocytosis can be of great utility for the diagnosis of BM involvement; additionally, this might also help to establish the real incidence of BM involvement in cutaneous mastocytosis.     

Bone Marrow Involvement in Lymphoma: The Importance of Marrow Magnetic Resonance Imaging

Detection of bone marrow involvement is important for staging and treatment decisions in patients with lymphoma. Although routine bone marrow evaluation is based on aspirates and bone marrow biopsies, new diagnostic tools are required to improve diagnostic accuracy. Visual and quantitative assessment of the bone marrow by magnetic resonance (MR) imaging is useful for the detection of occult lymphomatous marrow involvement. MRI is also suitable for the evaluation of disease extent in the bone marrow. Furthermore, abnormal images on marrow MRI may be associated with a significantly poorer survival in patients with lymphoma, regardless of histologic findings in the marrow. Evaluation of the bone marrow by MRI is essential to assess disease status in patients with lymphoma.     

Micrometastases in bone marrow of patients with suspected pancreatic and ampullary cancer

AIMS: This prospective study aimed to evaluate the detection of micrometastases in bone marrow of patients with suspected pancreatic and ampullary cancer and to determine their predictive value on overall survival. METHODS: Between December 1997 and December 1998, 35 patients (19 male, 42-77 years) with suspected pancreatic and ampullary cancer underwent diagnostic laparoscopy as a final staging procedure before exploration. Bone marrow was aspirated from the iliac crest at the beginning of laparoscopy. Mononuclear cells were isolated and stained using the specific monoclonal antibody CAM 5.2. RESULTS: Cytokeratin-positive cells were detected in 12/35 (34%) of all patients. In the 31 patients with a final diagnosis of carcinoma, a positive staining was found in 10/31 (32%) of the bone marrow aspirates. After a median follow-up of 17 months (2-24), 15/31 (48%) patients had died: 7/10 (70%) with and 8/21 (38%) without micrometastases (* P<0.04). All four patients who turned out to have chronic pancreatitis were alive without malignancy. In two of these four patients, distinct cytokeratin-positive cells were seen. CONCLUSIONS: Micrometastases in bone marrow of patients with the final diagnosis pancreatic or ampullary carcinoma seem to predict a significantly shorter survival. However, clinical use of cytokeratin markers cannot be recommended at present, because false-positive staining was found.     

Subperiosteal aneurysmal bone cyst with associated bone marrow oedema: An unusual appearance

A case of a subperiosteal aneurysmal bone cyst with adjacent bone marrow oedema is presented. Aneurysmal bone cysts have been well documented in the published literature; however, relatively few have been observed in a subperiosteal location, and associated bone marrow oedema in the absence of a demonstrable pathological fracture is a rare finding. Aneursymal bone cyst should be considered in the differential diagnosis of subperiosteal bone lesions and may be associated with bone marrow oedema.     

Clinical significance of proliferative potential of occult metastatic cells in bone marrow of patients with breast cancer

There is increasing statistical evidence that the presence of tumour cells in bone marrow detected by immunocytochemistry represents an important prognostic indicator in breast cancer, but their individual capacity to become clinical metastases is unknown. The aim of this study was to assess the proliferative capacity of these occult metastatic cells in the bone marrow of patients with various stages of breast cancer. We obtained bone marrow aspirates from 60 patients with breast cancer before treatment with chemotherapy: 17 stage II, 12 stage III and 31 stage IV. After bone marrow culture for 6-34 days (median: 17 days) under specific cell culture conditions, viable epithelial cells were detected by cytokeratin staining in 40 patients (66%). Expansion of tumour cells was poorly correlated with tumour cell detection on primary screening (P=0.06). There was a nonsignificant correlation between the number and the presence of expanded tumour cells and the UICC stage of the patients. On primary screening, tumour cell detection was positive in 56% of patients and was correlated with clinical UICC stage (P=0.01). However, with a median follow-up of 23 months, expansion of tumour cells from bone marrow was associated with decreased patient survival (P=0.04), whereas the survival difference according to detection of CK-positive cells on primary screening was not statistically significant. In conclusion, viable tumour cells can be detected in the bone marrow of breast cancer patients. Their proliferative potential could be predictive of outcome and deserves further investigation.     

骨髓涂片和流式细胞术在神经母细胞瘤骨髓转移微小病灶检测中的临床应用

目的:探讨骨髓涂片和流式细胞术在神经母细胞瘤骨髓转移微小病灶检测中的临床应用价值.方法:回顾性分析2019年01月至2020年10月我院收治的经病理确诊为神经母细胞瘤患者126例,收集患者临床资料,特别是在治疗期间同时同部位进行骨髓穿刺行骨髓涂片和流式细胞术(flow cytometry,FCM)检测,分析两种方法在神...     

EB病毒感染相关性噬血细胞综合征的骨髓细胞学特点分析

目的:探讨分析EB病毒感染相关性噬血细胞综合征的骨髓细胞学特点。方法:选择我院收治的EB病毒感染相关性噬血细胞综合征患者47例作为观察组,50例健康人群作为对照组,分析噬血细胞综合征患者临床表现、EB病毒检测情况以及骨髓细胞学特征,并比较两组受试者实验室相关指标差异。结果:47例EB病毒感染相关性噬血细胞综合征患者中,均出现发热、脾肿大以及血清铁蛋白增高。47例患者平均EBV-DNA定量为（8.23±2.33）×105 copies/ml,患者EBV-DNA检测结果均为阳性。两组受试者血常规指标WBC、PLT、Hb以及凝血功能指标APTT、PT、TT、FIB比较均具有显著差异（P<0.05）。47例EB病毒感染相关性噬血细胞综合征患者中,其中33例出现骨髓增生活跃,14例出现骨髓增生减低,47例患者骨髓图片中均可见噬血细胞。结论:EB病毒感染相关性噬血细胞综合征患者临床诊断应结合临床表现、EB病毒抗体检测、临床生化指标分析以及骨髓细胞学检查等综合手段进行分析,其中骨髓细胞学形态变化是临床诊断的要点。     

评价全身FDG-PET/CT在诊断淋巴瘤患者骨髓浸润中的价值

目的:本研究旨在评价PET-CT和骨髓涂片、骨髓活检、免疫分型结果诊断淋巴瘤的一致性和相关性。方法:收集临床确诊淋巴瘤患者的详细临床信息,包括姓名、性别、年龄、淋巴瘤细胞起源、病理分型、临床分期、行为状态、有无B症状、血LDH水平、血β2微球蛋白水平、骨髓涂片结果、免疫分型结果、骨髓活检结果以及详细的PET-CT影像学描述等。根据不同临床信息为患者进行详细分层,评价影响PET-CT中骨髓摄取葡萄糖的因素、影响淋巴瘤骨髓浸润的因素。设定骨髓涂片、骨髓活检、免疫分型阳性为对照,探究PET-CT在诊断淋巴瘤患者骨髓浸润中的价值。分别探讨PET-CT对于诊断不同病理类型淋巴瘤患者骨髓浸润的差异。结果:在性别、病理类型、细胞起源、有无B症状及骨髓浸润等不同分层中,只有淋巴瘤骨髓浸润与PET-CT中骨髓葡萄糖摄取有密切相关性(P=0.002)。而骨髓浸润与年龄(P=0.017)密切相关。设定骨髓涂片、骨髓活检、免疫分型阳性为对照,PET-CT检测淋巴瘤总体骨髓浸润的敏感度为54.3％、特异度为80.5％、准确度为74.5％,并且在不同病理类型中差异显著。PET-CT可以与骨髓涂片、骨髓活检、免疫分型共同指导淋巴瘤临床分期。结论:PET-CT中的骨髓葡萄糖摄取对淋巴瘤骨髓浸润及临床分期有一定的指导意义。不同病理类型的淋巴瘤中,PET-CT与骨髓涂片、骨髓活检、免疫分型的一致性不尽相同。PET仍不能完全取代骨髓涂片、骨髓活检、免疫分型。     

Prostatic carcinoma metastatic to bone: sensitivity and specificity of prostate-specific antigen and prostatic acid phosphatase in decalcified material

Decalcified bone marrow biopsies containing metastatic tumor from 36 patients were stained for prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) using the avidin biotin complex (ABC) immunoperoxidase technique. Of these patients, 22 had known prostate primaries, ten had known nonprostatic, and four female patients had unknown primaries. Prostate-specific antigen was identified in 86% (19/22) of the metastatic prostatic carcinomas. Prostatic acid phosphatase was present in only 36% (8/22). None of the patients with nonprostatic primaries or unknown primaries showed positive staining for either antigen (0/14). This study indicates that immunoperoxidase staining for PSA is very sensitive and specific in the diagnosis of metastatic prostate carcinoma, while PAP was less sensitive using decalcified bone marrow specimens. We believe that immunostaining with PSA should be of great value in diagnosis of prostatic carcinoma metastatic to the bone.     

Magnetic resonance imaging of bone marrow versus bone marrow biopsy in malignant lymphoma

Bone marrow involvement is a frequent finding in malignant lymphoma. Bone marrow biopsy of the posterior iliac crest is routinely performed for staging. Abnormal magnetic resonance imaging (MRI) signals of bone marrow was also reported to be indicative of bone marrow involvement. This study included 60 patients with malignant lymphoma. Unilateral bone marrow biopsy of the posterior iliac crest was performed. MRI of lumbar spine was studied within 24 hours of bone marrow biopsy. 22 healthy controls were used for the detection of MRI objectivity during visual evaluation. In 83% of patients (50/60), biopsy and MRI results agreed completely. In two patients, histologic sections failed to show any evidence of bone marrow involvement despite abnormal MRI signals suggestive of involvement. In three patients, MRI was completely normal despite biopsy proven bone marrow infiltration. False negativity (3/60) and false positivity (2/60) rates were very low. Negative biopsy findings with positive or equivocal MRI results should not exclude bone marrow involvement and needs further evaluation with bilateral or guided biopsy. Thus, we conclude that MRI of bone marrow is a fairly sensitive, noninvasive modality and might be of potential value in detecting bone marrow infiltration in malignant lymphoid neoplasms which can be utilized as a useful adjunct to standard staging procedures.     

Comparison of monoclonal antibodies for the detection of occult breast carcinoma metastases in bone marrow

Summary Twenty percent (n = 6) of Stage III or IV breast cancer patients (n = 30) had bone marrow metastases detected in bilateral bone marrow biopsy/aspiration preparations using standard histologic preparations. Each metastasis was also detected by four separate monoclonal antibodies (MAbs) which recognize breast carcinoma associated antigens (DF3, anti-EMA, HMFG-2, and CAM5.2). These MAbs were then utilized to stain other bone marrow preparations (n = 81) to determine their utility for the detection of micrometastatic breast carcinoma. MAbs HMFG-2, anti-EMA, and DF3 were each strongly reactive with bone marrows containing histologically-evident metastatic breast carcinoma (18/18). These anti-epithelial membrane antigen MAbs, however, were also reactive with rare plasma cells and immature cells (as well as cell clusters) in some of the control bone marrow samples tested, including those from normal patients and patients with hematologic disorders. They also reacted with some of the preparations from patients with leukemia and lymphoma, and with uninvolved marrows from patients with non-epithelial malignancies. The anti-keratin MAb CAM5.2, in contrast, reacted with 83% (15/18) breast cancer metastases and failed to stain any cells in the various categories of control marrow preparations. These data suggested that MAb CAM5.2 might be utilized to immunohistochemically differentiate micrometastatic breast carcinoma from immature myeloid or erythroid elements.Each MAb was then reacted with histologically uninvolved marrow preparations from the remaining 24 of 30 breast cancer patients in an attempt to identify occult breast carcinoma metastases. While MAbs HMFG-2, DF3, and anti-EMA demonstrated reactive cells in some of these marrows, this reactivity was similar to that seen with control preparations. MAb CAM5.2, in contrast, was negative with all specimens. These data suggest that MAb CAM5.2 may be a useful immunologic probe for the detection and confirmation of metastatic breast carcinoma in bone marrow, while more caution must be employed in the interpretation of results obtained using MAbs anti-EMA, DF3, and HMFG-2.