1. Biopsy
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01. Dysplastic features in megakaryocyte maturation: bone marrow aspirate
02. Dysplastic features in megakaryocyte maturation: bone marrow aspirate
03. Thoracoscopic examination in right-sided pleural mesothelioma
04. Chronic idiopathic myelofibrosis
05. Chronic eosinophilic leukemia/hypereosinophilic syndrome: bone marrow biopsy
06. Orientation and marking of surgical breast specimens for the pathologist
07. Chronic idiopathic myelofibrosis
08. Pseudoprogression of germ cell tumor: malignant teratoma
09. Chronic eosinophilic leukemia/hypereosinophilic syndrome: bone marrow biopsy
10. Inflammatory breast carcinoma
11. Essential thrombocythemia: peripheral blood smear
12. Essential thrombocythemia: diagnosis
13. Advanced Paget's disease of the breast
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2. Dysplastic features in megakaryocyte maturation: bone marrow aspirate
Figure 1-7. Dysplastic features in megakaryocyte maturation in bone marrow aspirate (A) and biopsy (B) include nuclei with monolobate (A) or hyposegmented forms (B), with corresponding features noted in biopsy (arrows). (Aspirate: Wright-Giemsa stain, original magnification ×100; Biopsy: Hematoxylin and eosin stain, original magnification ×100).

3. Dysplastic features in megakaryocyte maturation: bone marrow aspirate
Figure 1-7. Dysplastic features in megakaryocyte maturation in bone marrow aspirate (A) and biopsy (B) include nuclei with monolobate (A) or hyposegmented forms (B), with corresponding features noted in biopsy (arrows). (Aspirate: Wright-Giemsa stain, original magnification ×100; Biopsy: Hematoxylin and eosin stain, original magnification ×100).

4. Thoracoscopic examination in right-sided pleural mesothelioma
Figure 7-6. Thoracoscopic examination. For patients with a large effusion and no dominant mass in the lung, video-assisted thoracoscopy has become the preferred method of diagnosis. Thoracoscopic examination allows the surgeon to evaluate specific areas for guided biopsy and to assess the ability of the lung to expand. A, Thoracoscopic view of a right pleural mesothelioma. Multiple nodules on the chest wall, diaphragm, and lung are seen, as well as pleural effusion.Large biopsies can be taken that can then be analyzed with the proper pathologic markers. Extent of disease with regard to the diaphragm, pericardium, chest wall, and nodes can give further staging information. If there is no free pleural space because of previous treatment of pleural effusion and the bulk of the disease in the hemithorax is solid, open biopsy is usually required. Such a biopsy should be carefully planned such that the scar could be incorporated into the definitive incision if a major resection is considered after definitive diagnosis. If the patient refuses definitive surgical therapy, obliteration of the pleura cavity through sclerotherapy with asbestos-free talc can decrease pleural effusion if the underlying lung can expand. B, View of the pleura after talc poudrage at the time of thoracoscopy in the patient depicted in A. A success rate of 80% to 100% can be expected with success being defined as no further need for tapping after 1 month; however, the median survival after this treatment ranges from 7 to 9 months [4],[5]. References: [4]. Canto A, Guijarro R, Arnau A, et al. Videothoracoscopy in the diagnosis and treatment of malignant pleural mesothelioma with associated pleural effusions. Thorac Cardiovasc Surg [5]. Charvat JC, Brutsche M, Frey JG, Tschopp JM, [Value of thoracoscopy and talc pleurodesis in diagnosis and palliative treatment of malignant pleural mesothelioma.] Schweiz Rundsch Med Prax

5. Chronic idiopathic myelofibrosis
Figure A, Peripheral blood smear showing the classic morphologic features seen in patients with chronic idiopathic myelofibrosis (CIMF), including leukoerythroblastosis with teardrop red blood cells. The arrowheads highlight metamyelocyte, circulating nucleated red blood cell, and teardrop red blood cells (Wright-Giemsa stain, X400). B, Bone marrow biopsy from a patient with the fibrotic phase of CIMF showing hypocellularity with extensive interstitial fibrosis and osteosclerosis (hematoxylin and eosin stain, X40). The megakaryocytes are markedly increased in number with clustering and significant variation in their size and shape; some contain hyperlobulated and hyperchromatic nuclei. C, Markedly increased bone marrow interstitial reticulin fibrosis (reticulin stain, X100). D, Bone marrow biopsy from a patient with fibrotic phase of CIMF showing the presence of collagen fibers (trichrome staining, X100). E, Bone marrow biopsy from a patient with cellular phase of CIMF. The bone marrow is markedly hypercellular with hyperplastic megakaryopoiesis (hematoxylin and eosin stain, X100; special staining revealing increased interstitial reticulin fibrosis is not shown). The characteristic megakaryocytes seen usually in the fibrotic phase of CIMF are considered a key diagnostic feature for the diagnosis of cellular phase of CIMF. Typically, these megakaryocytes demonstrate marked variability in size and shape as well as hyperlobulated and hyperchromatic nuclei.

6. Chronic eosinophilic leukemia/hypereosinophilic syndrome: bone marrow biopsy
Figure 6-16.A, Bone marrow biopsy from a patient with chronic eosinophilic leukemia (CEL)/hypereosinophilic syndrome (HES) demonstrating hypercellularity with markedly increased interstitially distributed eosinophils of unremarkable morphologic features (hematoxylin and eosin stain, X100). B, The bone marrow aspirate smear demonstrates marked eosinophilia with occasional left-shift. The morphologic features of the eosinophils in general are unremarkable (Wright-Giemsa stain, ×200).

7. Orientation and marking of surgical breast specimens for the pathologist
Figure 1-5. Orientation and marking of breast specimens. After an excisional biopsy, lumpectomy, or mastectomy, it is important to orient the specimen for the pathologist. In this case, silk sutures mark the edges in two places (one commonly used orientation is one short silk suture for the “superior” edge and one long silk suture for the ‘lateral” edge). It is important that the pathologist uses several different ink colors to mark the six margins (anterior, posterior, superior, inferior, medial, and lateral) so in the event that an excisional biopsy reveals ductal carcinoma in situ (DCIS) or infiltrating cancer, the distance to the margins can be measured. Failure to mark the specimen in an appropriate fashion or failure to use different colors of ink for the margins may result in more extensive surgery should a close margin (< 1 mm) be identified [5]. For example, instead of just having to reexcise a close inferior margin, if appropriate marking does not take place, then the whole cavity needs to be excised, creating the potential for more deformity of the breast. References: [5].National Comprehensive Cancer Network,
In Clinical Practice Guidelines in Oncology
vol Vol

8. Chronic idiopathic myelofibrosis
Figure A, Peripheral blood smear showing the classic morphologic features seen in patients with chronic idiopathic myelofibrosis (CIMF), including leukoerythroblastosis with teardrop red blood cells. The arrowheads highlight metamyelocyte, circulating nucleated red blood cell, and teardrop red blood cells (Wright-Giemsa stain, X400). B, Bone marrow biopsy from a patient with the fibrotic phase of CIMF showing hypocellularity with extensive interstitial fibrosis and osteosclerosis (hematoxylin and eosin stain, X40). The megakaryocytes are markedly increased in number with clustering and significant variation in their size and shape; some contain hyperlobulated and hyperchromatic nuclei. C, Markedly increased bone marrow interstitial reticulin fibrosis (reticulin stain, X100). D, Bone marrow biopsy from a patient with fibrotic phase of CIMF showing the presence of collagen fibers (trichrome staining, X100). E, Bone marrow biopsy from a patient with cellular phase of CIMF. The bone marrow is markedly hypercellular with hyperplastic megakaryopoiesis (hematoxylin and eosin stain, X100; special staining revealing increased interstitial reticulin fibrosis is not shown). The characteristic megakaryocytes seen usually in the fibrotic phase of CIMF are considered a key diagnostic feature for the diagnosis of cellular phase of CIMF. Typically, these megakaryocytes demonstrate marked variability in size and shape as well as hyperlobulated and hyperchromatic nuclei.

9. Pseudoprogression of germ cell tumor: malignant teratoma
Figure Pseudoprogression. Some patients with germ cell tumors may exhibit a pseudoprogression that may lead an investigator to inappropriately initiate salvage therapy. Common scenarios include those patients with a growing teratoma (without rise of serum markers). This growth is most often observed in patients with malignant transformation of teratoma and mediastinal germ cell tumors. A mass that was not apparent on initiation of therapy for a primary mediastinal tumor is shown here. Despite normalization of serum markers, the mass grew through the sternum. Biopsy revealed malignant transformation of teratoma.

10. Chronic eosinophilic leukemia/hypereosinophilic syndrome: bone marrow biopsy
Figure 6-16.A, Bone marrow biopsy from a patient with chronic eosinophilic leukemia (CEL)/hypereosinophilic syndrome (HES) demonstrating hypercellularity with markedly increased interstitially distributed eosinophils of unremarkable morphologic features (hematoxylin and eosin stain, X100). B, The bone marrow aspirate smear demonstrates marked eosinophilia with occasional left-shift. The morphologic features of the eosinophils in general are unremarkable (Wright-Giemsa stain, ×200).

11. Inflammatory breast carcinoma
Figure 1-3. Inflammatory carcinoma. Inflammatory carcinoma represents 1% to 3% of all patients diagnosed with breast cancer. The diagnosis is based on the clinical presentation of erythema and edema of the skin (peau d’orange). Whereas in some cases a dominant mass may be present, in most situations, there is diffuse infiltration of the breast with tumor and no discrete tumor. The diagnosis is confirmed by core biopsy; however, in the past, as pictured here, excision biopsy with skin was used to confirm the diagnosis but is no longer necessary. Dermal lymphatic invasion is commonly seen when the skin is biopsied, but this feature may be absent and is not necessary to make the diagnosis of inflammatory cancer if the clinical features listed above are present. Mammography may or may not reveal a distinct mass and instead may only demonstrate skin thickening and edema. The treatment is multi-modal with initial primary systemic chemotherapy followed by modified radical mastectomy (and the option for immediate reconstruction) and chest wall radiation. Five-year survival rates and local control have improved markedly with the introduction of this approach [3]. References: [3]. Hortobagyi GN, Singletary SE, Strom EA, : Treatment of locally advanced and inflammatory breast cancer. In Diseases of the Breast, edn 3. Edited by Harris JR, Lippman ME, Morrow M, Osborne CK. Philadelphia: Lippincott, Williams & Wilkins; 2004

12. Essential thrombocythemia: peripheral blood smear
Figure 6-5. A, By definition, the platelet count is more than 600,000/μL in the peripheral blood from essential thrombocythemia (ET) patients. B, Bone marrow biopsy from a patient with ET. The bone marrow is markedly hypercellular with a remarkable increase in megakaryocytes. Large megakaryocytes with hyperlobulated nuclei are a common finding in ET. Evidence of bone marrow fibrosis is not seen (hematoxylin and eosin stain, ×40).

13. Essential thrombocythemia: diagnosis
Figure 6-3. Essential thrombocythemia (ET) is a clonal disorder of unknown etiology involving a multipotent hematopoietic progenitor cell characterized by pronounced megakaryocytic hyperplasia in the bone marrow and striking peripheral thrombocytosis [7]. ET is a diagnosis of exclusion. Therefore, reactive and secondary causes (ie, other disease) for thrombocytosis must first be excluded (by checking, for example, serum ferritin and C-reactive protein levels, and peripheral blood smear). Bone marrow biopsy is required next (practical ET diagnostic algorithm incorporating pertinent tests is shown). The diagnosis of ET can be made if platelet count is persistently at least 600 ×109/L; there is no cause for reactive thrombocytosis found; hematocrit is less than 40% or red cell mass (mL/kg) is less than 36 for males and 32 for females; red cell mean corpuscular volume, or serum ferritin or marrow iron stain are normal; fibrosis in bone marrow is absent or less than one third of biopsy area without splenomegaly and leukoerythroblastic reaction in blood; no myelodysplastic changes on bone marrow smear are found; no BCR-ABL gene rearrangement is present. References: [7]. Gisslinger H, Update on diagnosis and management of essential thrombocythemia. Semin Thromb Hemost

14. Advanced Paget's disease of the breast
Figure 1-2. Advanced Paget’s disease. The entire areolar complex is replaced with the disease process described by Sir James Paget in 1874 [1]. Patients classically present with eczematous changes of the nipple that can progress to bleeding and ulceration as pictured in this case. The vast majority of patients, more than 90%, have an underlying carcinoma (in situ or invasive), and a mammogram is warranted to assess for deeper disease in the breast. Traditionally, surgical treatment has been mastectomy with or without axillary dissection; however, if patients do not have evidence of deeper disease on clinical examination or mammography then breast conservation with radiation results in similar local control and survival rates. Axillary sampling, with sentinel node biopsy, is based on whether the patient has invasive or in situ disease [2]. References: [1]. Paget J, On disease of the mammary areola preceding cancer of the mammary gland. St Bartholomews Hosp J [2]. Kawase K, DiMaio DJ, Tucker SL, et al. Paget’s disease of the breast: there is a role for breast-conserving therapy. Ann Surg Oncol