原发性骨髓纤维化误诊为脾功能亢进行脾切除1例并文献复习

目的:学习原发性骨髓纤维化(primary myelofibrosis,PMF)和脾功能亢进的诊断及鉴别诊断.方法:对1例PMF患者进行临床资料、骨髓病理及基因检测总结,并结合文献对其诊断及鉴别诊断进行学习.结果:PMF时骨髓造血功能差,肝、脾增大是身体代偿性的髓外造血,并非脾功能亢进,不可盲目行脾切除术.结论:对有原因不明的脾大患者,诊断依据要充分,需进一步行骨髓涂片、骨髓活检以及基因学检查,排除PMF.     

胰腺髓系细胞肉瘤临床病理特点

目的探讨胰腺髓系细胞肉瘤的临床病理特点,鉴别诊断要点。方法结合文献对1例胰腺髓系细胞肉瘤的临床资料、病理特征、免疫表型及治疗预后进行分析。结果胰腺髓系细胞肉瘤是一种罕见肿瘤,迄今仅查到8例报道。本例表现为胰头部浅绿色占位病灶。瘤细胞弥漫性分布或列兵式竹节样排列。细胞分化程度不等,以原始未成熟细胞为主,可找到幼稚嗜酸性粒细胞。免疫组化瘤细胞表达CIM5、CIM3、MPO、Lys、CD117、CD34及CD15等,不表达CD790t、CD3、CD30等。结论仅凭常规形态学观察,髓系细胞肉瘤易误诊为淋巴瘤,小细胞癌,ES／PNET等。细胞分化程度不等,列兵式排列,幼稚嗜酸性细胞的出现是重要的诊断线索。免疫组化是获得正确诊断的主要依据。即使病变位于局部仍需行抗自血病化疗。     

Fusarium solani infection as an initial manifestation of AML transformation in myelodysplastic syndrome: A case report

Severely immunocompromised patients are at increased risk for uncommon infectious diseases with atypical presentations. Fusarium sp., has been reported in patients with hematological malignancies and prompt diagnosis is necessary due to high mortality. We report a myelodysplastic syndrome (MDS) patient who presented Fusarium solani infection associated with granulocytic sarcoma as an initial presentation of acute myeloid leukemia (AML) transformation. We performed histological examination, immunohistochemistry analysis, culture of the biopsy tissue and DNA sequencing to make a conclusive diagnosis of F. solani and granulocytic sarcoma, reinforcing the necessity of performing complete evaluation of skin lesions in immunocompromised patients.     

A novel immunohistochemical sequential multi-labelling and erasing technique enables epitope characterization of bone marrow pericytes in primary myelofibrosis

Madelung A, Bzorek M, Bondo H, Zetterberg E, Bjerrum O W, Hasselbalch H C, Scheding S & Ralfkiaer E
(2012) Histopathology  60, 554–560
A novel immunohistochemical sequential multi‐labelling and erasing technique enables epitope characterization of bone marrow pericytes in primary myelofibrosis Aim: In Philadelphia (Ph)‐negative chronic myeloproliferative neoplasms, increased microvascular density, bizarre vessel architecture and increased number of pericytes are among the distinct histopathological features. The aim of this study was to characterize bone marrow pericytes in primary myelofibrosis (PMF) using a novel multi‐labelling immunohistochemical technique. Methods and results: Bone marrow biopsies from a normal donor (n = 1) and patients with PMF (n = 3) were subjected to an immunohistochemical sequential multi‐labelling and erasing technique (SE‐technique). Antigens of interest in the first and/or second layer were detected with an immunoperoxidase system and visualized with aminoethylcarbazole. After imaging, erasing and blocking of immunoreagents, the slides were stained with a traditional double immunolabelling procedure. In addition, we applied a Photoshop^® colour palette, creating a single composite image of the sequential staining procedures. We successfully applied four layers of antibodies on one slide using CD146, smooth muscle actin, CD34, CD271 and Ki67 in different combinations. The SE‐technique significantly improves morphological and phenotypical studies in bone marrow specimens. Conclusions: To our knowledge, the SE‐technique is the first to multi‐label antigens, identifying vessel and pericyte architecture in bone marrow by light microscopy. This technique may unravel novel aspects of the composition of the microvessel structures in patients with PMF and related neoplasms.     

Histopathological characterization of aortic intimal sarcoma with multiple tumor emboli

A case of aortic intimal sarcoma with multiple tumor emboli and distal metastasis is reported. All metastasis (adrenal, spleen) were via the arteries. This case also had independent lung cancer. Macroscopically, the aortic tumor did not form a bulged mass, but had linear ulceration with abundant mural thrombi. Poorly cohesive large atypical cells were seen in the intima of the abdominal aorta without invasion into the media. Tumor cells were disseminated into the mural thrombi on the aorta and embolized its branches. In the metastatic tumor or tumor emboli of the distal artery, there were not only large atypical cells, but also the foci of spindle-shaped cells or epithelioid differentiation. Tumor cells in the aorta were immunohistochemically positive for only vimentin. Muscle-specific actin was positive focally for spindle-shaped cells of tumor emboli and metastatic tumors. Furthermore, cytokeratin-positive cells were scatteredly seen. All tumor cells were negative for factor VIII and did not have a histologic or phenotypic analogy with lung cancer. The primary intimal sarcoma in the present case was of undifferentiated non-endothelial intimal stromal cell origin, and may have had multipotential for differentiation. Investigation of the metastatic site was useful for recognizing the features of this tumor.     

Ovarian granulocytic sarcoma as the primary manifestation of acute myelogenous leukemia

Granulocytic sarcoma (GS) usually occurs concomitantly with or after the onset of acute myeloid leukemia (AML) or other myeloproliferative disorders, however, GS of the ovary as the primary manifestation of AML is exceedingly rare. To the best of our knowledge, eight cases of ovarian GS as the first sign of AML have been reported in the literature. Here, we report the ninth case: a 27-year-old female who presented with an ovarian mass without any underlying hematologic disorder. A high index of suspicion aided by immunohistochemistry established the correct diagnosis of undifferentiated GS that involved the ovary. Simultaneously, laboratory findings indicated that the blood counts continually increased after surgery. Five days after the surgery, bone marrow biopsy confirmed the presence of AML. After establishing the diagnosis, the patient was sent to the hematology department to receive cytosine arabinoside and idarubicin chemotherapy. This report outlines an exceedingly rare case of AML that initially manifested as an ovarian GS. Awareness of this entity will enable earlier diagnosis and appropriate treatment.     

An isolated sacral promyelocytic sarcoma in a child: A rare case report with emphasis on cytomorphology

Myeloid sarcoma (MS) is an uncommon localized extramedullary tumor composed of immature myeloid precursor cells that can affect any organ. Promyelocytic sarcoma (PS), an extremely rare subtype of MS, is characterized by immature myeloid cells with features of acute promyelocytic leukemia (APL). We describe a case of pediatric PS that presented as a solitary sacral mass without any evidence of systemic or bone marrow involvement. The cytopathologic evaluation using touch imprint demonstrated numerous blasts with bilobed nuclei, cytoplasmic hyper-granularity, and aggregates of Auer rods, which are typical cytomorphologic features of APL. Herein, we report an extremely rare case of isolated PS in a child, emphasizing the importance of cytomorphologic evaluation, which is complemented by the findings from a comprehensive work-up.     

Extra-medullary myeloid tumour (granulocytic sarcoma) is often misdiagnosed: a study of 26 cases

AIMS: To describe the clinicopathological and immunophenotypic features of 26 cases of extra-medullary myeloid tumour (EMMT)/granulocytic sarcoma, which remains poorly recognized and is frequently confused with malignant lymphoma, and to discuss the main diagnostic problems experienced by the referring pathologist. METHODS AND RESULTS: Haematoxylin and eosin (H & E) sections of 26 cases of EMMT were re-examined. Immunostains for myeloperoxidase, lysozyme, neutrophil elastase, LCA, CD79a, CD20, CD43, CD45RO, CD3, CD30, CD15, CD68, MAC387, VS38C, MIC2, and the Leder stain for naphthol-ASD-chloroacetate esterase were performed on all cases. Clinical and follow-up data were obtained through a questionnaire to the referring pathologist or from the notes of the patients where available. In the 10 cases with known myeloproliferative disease, the initial diagnosis was correct in 10 whereas all cases presenting with EMMT without a previous history of myeloproliferative disorder had an initial incorrect diagnosis. The most common suggested diagnosis was that of a non-Hodgkin's lymphoma. The morphology of the tumours varied from well differentiated which included all stages of myeloid differentiation to poorly differentiated or blastic showing little or no evidence of myeloid differentiation. The proportion of positive cells for each stain varied. Chloroacetate esterase, myeloperoxidase and CD15 stained a large proportion of cells of the majority of the well differentiated tumours and a smaller proportion of the poorly differentiated/blastic tumours with very focal staining of some of the cases. Lysozyme and CD43 were the most sensitive of the markers staining a large proportion of cells of the majority of the tumours in both groups. Neutrophil elastase was the least sensitive of the markers of myeloid differentiation. CD79a, CD20, CD3 and CD30 were negative in all cases. CD43 was positive in all cases. CD68 stained a substantial number of cells in the majority of tumours. A smaller proportion of the tumours stained with MAC387. Four of the tumours showed positivity for MIC2. One tumour was positive for VS38C. CONCLUSION: This series documents continuing difficulties in the diagnosis of EMMT. Even well differentiated tumours are frequently mistakenly diagnosed as malignant lymphomas when they present without any history of antecedent myeloproliferative disorder. Careful evaluation of morphology for evidence of myeloid differentiation and a high index of suspicion when confronted with a less differentiated neoplasm are required to avoid this important diagnostic error. We suggest that a panel which includes chloroacetate-esterase, myeloperoxidase, lysozyme and CD43, together with other B- and T-lineage markers, in particular CD79a and CD3 should be used to confirm the diagnosis.     

Cerebrospinal fluid examination in a case of childhood orbital granulocytic sarcoma

The diagnosis of a case of childhood orbital granulocytic sarcoma, initially classified as a poorly-differentiated malignant tumor, was finally considered at the time of relapse following primary treatment with chemotherapy and local irradiation. At this time, systematic cerebrospinal fluid examination showed numerous blast cells with Auer rods, consistent with the diagnosis of meningeal acute myeloid leukemia of M2 type, and concomitant biopsy of the tumor indicated the diagnosis of chloroma. Reevaluation of the primary biopsy confirmed this diagnosis. Diagn Cytopathol 1996;15:237–240. © 1996 Wiley-Liss, Inc.     

Sclerosing extramedullary hematopoietic tumor presenting as an inguinal mass in a patient with primary myelofibrosis: a diagnostic pitfall

Sclerosing extramedullary hematopoietic tumor (SEMHT) is a rare lesion and presented as retroperitoneal or serosal-based mass. A 53-year-old man with a long history of primary myelofibrosis, presented with abdominal distension and inguinal mass. Pathologic examination of inguinal mass revealed a prominent sclerotic background with thick collagen deposits and mono, bi, or tri-lineage hematopoietic tissue containing atypical megakaryocytes and variable proportions of myeloid and erythroid series. The atypical megakaryocytes were positive for Factor VIII and CD61. SEMHT may be misdiagnosed as lymphocyte depleted Hodgkin’s disease, as a mesenchymal neoplasm, or as carcinoma, because of the presence of large atypical cells and marked fibrosis when clinical information regarding PMF is unknown. Awareness of the bizarre atypical megakaryocyte morphology with immature hematopoietic cells and of clinical history is essential to prevent misdiagnosis.     

Pulmonary manifestation of a Langerhans cell sarcoma: case report and review of the literature

In the following, we describe the very rare case of Langerhans cell sarcoma (LCS) in the lung. Throughout the medical literature, only a few cases have been published, and, to the best of our knowledge, this is the first case to be reported in Germany. The patient was an 81-year-old man who showed symptoms such as chronic cough and weight loss. Clinical examination including needle biopsy indicated a high possibility of carcinoma in the right lung and in the mediastinum; however, the final histopathological diagnosis after immunohistochemistry gave evidence of LCS. LCS is a neoplastic proliferation of Langerhans cells with malignant cytological features exhibiting a very aggressive behaviour. LCS can be distinguished from other carcinomas, lymphomas and sarcomas by the typical morphological features of Langerhans cells and the immunophenotype with a consistent expression of S-100 protein and CD1a. In contrast to Langerhans cell histiocytosis, the LCS consists of Langerhans cells with high atypia and a very high mitotic rate.     

Ganglion cells in Ewing's sarcoma following chemotherapy: A case report

A case of Ewing's sarcoma of the bone, arising in the right radius of a 12-year-old girl, which showed unique histologic features after pre-operative treatment, is reported. The light microscopic features of a biopsy sample were those of a small round cell tumor showing positive immunoreaction with antibodies against the product of the MIC 2 gene (O13), neuron-specific enolase, neurofilament, and synaptophysin, but no morphological differentiation. The patient received combined intensive multi drug chemotherapy and radiation before surgery. Examination of the surgical specimen showed that the tumor was less cellular than that in the biopsy specimen, and was composed mainly of loosely textured large cells mimicking ganglion cells, occasionally forming Homer-Wright rosettes. An lmmunohistochemical study revealed that neural differentiation was enhanced. Immunoreactivity for Leu-7 also became positive. Although the patient underwent postoperative chemotherapy, she died of multiple lung and bone metastases 30 months alter the diagnosis. Autopsy showed that metastatic foci were made up of densely packed small round cells like those seen In the biopsy samples, but associated with prominent Homer-Wright rosettes. To the authors' knowledge, this is the first report of a tumor being replaced almost entirely by ganglion cells after preoperative chemotherapy and radiotherapy.     

Nonhealing ulcer--a rare initial presentation of chronic myeloid leukemia diagnosed on aspiration cytology

Involvement of skin in hematologic malignancies is rare phenomena as majority of the dermatologic lesions in leukemia patients are nonleukemic. In the absence of preceding history of leukemia, the diagnosis is often a surprise. Chronic nonhealing ulcer on the back of a 65-years-old male prompted a fine needle aspiration from its base. Smears showed an unexpected picture comprising of leukocytes in various stages of maturation against a hemorrhagic background. A cytologic diagnosis of leukemia cutis was given. Subsequent hematologic investigations revealed chronic myeloid leukemia in chronic phase. Cutaneous involvement is a rare initial presentation of leukemia in an otherwise asymptomatic patient and also an uncommon cause of nonhealing ulcer. Aspiration cytology scores over biopsy in not only being a rapid and easy diagnostic tool but also allows better appreciation of cellular details like cytoplasmic granules.     

Diagnosis of myeloid sarcoma involving salivary glands by fine-needle aspiration cytology and flow cytometry: report of four cases

Myeloid sarcoma involving salivary glands is extremely rare. Here, we report four cases of this rare occurrence, diagnosed by fine-needle aspiration biopsy. All of four patients had previous diagnoses of myeloid neoplasms. They presented with a solitary mass in the parotid or submandibular salivary gland. The cytological evaluation of the aspirates revealed scattered salivary gland acini admixed with dispersed atypical cells. In three cases, the atypical cells appeared to be heterogeneous, intermediate to large in size, and have folded nuclei with fine chromatin. In another case the atypical cells were monotonous and had round nuclei with fine chromatin. The myeloid lineage of the atypical cells was demonstrated by flow cytometric analysis. High clinical suspicion, careful cytological evaluation, and concurrent ancillary studies are essential for establishing a diagnosis of myeloid sarcoma.     

Autopsy in the time of COVID

Whilst much literature has been published since the start of the COVID-19 pandemic, there remains limited knowledge of the autopsy findings following death from SARS-CoV-2 infection. The practicalities of triaging and examining bodies with suspected COVID-19 are complex and the need for full post-mortem must be balanced with the potential risks to mortuary staff. This brief case report describes the features of a COVID-19 autopsy performed at the start of the first phase of the pandemic and highlights some important learning points for trainees engaged in autopsy practice.     

Clinical management of primary odontogenic sarcoma in the mandible: a case report after WHO nomination

Ameloblastic fibro-odontosarcoma(AFOS)now designated as odontogenic sarcoma is an extremely rare odontogenic tumor,which histologically presents as a biphasic neoplasm with a malignant mesenchymal component plus ameloblastic epithelium.Here we report a 27-year-old Chinese female with the complaint of a painful swelling for half a month in the right mandible.A segmental mandibulectomy,with an immediate mandibular reconstruction using a free vascularized osteocutaneous fibular flap was performed using surgical guide models.Histological analysis revealed a primary odontogenic sarcoma.The postoperative period was uneventful,and no clinical indication of recurrence or metastasis was observed during the 3-year follow-up.No adjuvant therapy was proposed.This is the first odontogenic sarcoma case reported in China after the new World Health Organization classification of odontogenic lesions.     

Impaired NK cell differentiation of blood-derived CD34+ progenitors from patients with myeloid metaplasia with myelofibrosis

Cultured blood CD34(+) progenitors from patients with myeloid metaplasia with myelofibrosis (MMM) failed to differentiate into natural killer (NK) cells with recombinant interleukin (IL)-15. No NK cells either could be induced in coculture with IL-15-expressing fibroblasts from MMM patients' spleens. The impaired NK differentiation could be circumvented by using normal blood CD34(+) cells in the coculture. In this case, cell-to-cell contact and IL-15 interaction were crucial for NK cell differentiation. Pretreatment of normal CD34(+) progenitors with anti-IL-15 monoclonal antibody markedly reduced NK cell production while MMM fibroblast pretreatment did not. Both normal and MMM progenitors constitutively expressed IL-15. Analysis of endogenous IL-15 signaling pathway revealed a constitutive gammac/Jak3 association and STAT3 activation in the two types of progenitors. Anti-IL-15 monoclonal antibody treatment caused a downregulation of IL-15 signaling in normal but not MMM blood cells. The impaired NK differentiation in MMM may thus arise from a deregulated control of an endogenous IL-15 involved in hematopoietic progenitors' lymphoid differentiation.