[Allogeneic hematopoietic stem cell transplantations for relapsed and refractory acute lymphoblastic leukemia following inotuzumab ozogamicin treatment].

Inotuzumab ozogamicin (InO) was administered in three cases of relapsed/refractory adult acute lymphoblastic leukemia (ALL) before allogeneic hematopoietic stem cell transplantation (allo-SCT). One case developed extremely severe sinusoidal obstruction syndrome (SOS) but recovered after receiving defibrotide therapy. A gap of 63 days in the SOS case was noted from the last administration of InO to allo-SCT, the duration was 133 and 86 days for the other two cases, and the remaining risk factors for SOS were comparable in the three cases. In contrast to gemtuzumab ozogamicin (GO), the interval between InO exposure and allo-SCT has not been reported as a risk for SOS. Nevertheless, this case suggests that the intervals should be as long as possible.

Ultrasound Findings in Three Complex Cystic Breast Carcinomas: Correlation with Intrinsic Tumor Subtype.

In ultrasound examinations, mixed mammary gland masses are divided into either intracystic masses that contain a solid component in the cyst or solid masses that contain a fluid component in the mass. The histological types and subtypes of three complex cystic masses that showed different internal compositions in ultrasound were determined using the ultrasound findings of three patients. Case 1: The mass showed a large cystic component (bleeding) inside and a broad-based solid lesion at the margin in the ultrasound finding. The histological type was encapsulated papillary carcinoma and the subtype was luminal A. Case 2: The mass was lobulated with a small cystic component at the margin. The histological type was solid papillary carcinoma and the subtype was luminal A. Case 3: The mass was lobulated with a circumscribed margin. Cystic components suspected of being hemorrhagic necrosis were observed at the margin and within the solid component. The histological type was squamous cell carcinoma and the subtype was triple negative. Case 2 was a solid mass in appearance, but a cystic component noted at the margin was possibly an intracystic mass. For Case 3, findings suggestive of necrosis were observed both at the margin and in the solid component and this suggested a mass with fluid degeneration. Complex cystic masses are usually examined with a focus on the solid component seen on ultrasound images; however, it is also important to observe the cystic composition. This can help determine the subtypes in addition to the histological types.

Pure flat epithelial atypia is uncommon in subsequent breast excisions for atypical epithelial proliferation.

The management of atypical intraductal lesions of the breast remains controversial. In the present study, the subsequent surgical excision results and follow-up data on 86 (3.65%) atypical intraductal lesions and 78 (3.31%) low-grade ductal carcinoma in situ (DCIS) from a cohort of 2358 needle biopsies were examined. There were 17 cases (0.72%) of pure flat epithelial atypia (FEA), 44 (1.87%) pure atypical ductal hyperplasia (ADH), three (0.13%) pure atypical lobular hyperplasia (ALH), 18 (0.76%) combined ADH + FEA, three (0.13%) combined ALH + FEA and one (0.04%) combined ALH + FEA + ADH. Subsequent surgical excisions were done in 53 cases and revealed the following incidences of malignancy: pure FEA (1/8); pure ADH (17/31); FEA + ADH (7/10); FEA + ALH (2/3); and FEA + ALH + ADH (0/1), with pure FEA showing significantly lower incidence of malignancy. In this cohort, there were 703 carcinomas including 155 DCIS with 78 cases (50.3%) being low-grade. FEA with ADH (and/or ALH) was present in 22 (28.2%) of these 78 cases of low-grade DCISs at surgical excisions. Pure FEA was not detected in any of the subsequently excised surgical materials of the atypical intraductal lesions nor the low-grade DCISs. Thus, pure FEA was very unusual in surgical specimens. When pure FEA is detected at needle biopsy, a wait and see approach can be adopted. However, when the FEA is associated with other concomitant atypical intraductal lesions, especially ADH, further excision should be contemplated.

Cytological features of myxomatous fibroadenoma of the breast.

Fibroadenoma (FA) is a benign tumor that must be differentiated from carcinomas. FAs often exhibit myxedematous changes (myxomatous FA, M-FA). We previously reported on the clinical significance of M-FA. M-FA and (mucinous) carcinoma share clinical findings, rapid growth and a relatively large size, a high-depth/width (D/W) ratio, a relatively round shape, and posterior echo enhancement with internal hyperechogenicity on ultrasonography (US). Next, a biopsy is required for differential diagnosis. In this study, we evaluated the diagnostic significance of the cytological findings of M-FA with US findings. Among 13 FAs that were diagnosed by cytology, we compared (i) a group of six mucinous carcinomas with acellular mucin and a D/W ratio ≥ 0.7 (a suspicious factor for malignancy) with a group with a D/W ratio of <0.7, and (ii) the frequency of metachromasia on Giemsa stain between M-FAs and non-M-FAs among eight FA cases confirmed by histology. (i) FA lesions (7 of 13) showed metachromasia with Giemsa staining significantly more frequently than did mucinous carcinoma (0/6) (Fisher's exact test, P < 0.044). FA lesions with a D/W ratio ≥ 0.7 (6/7) showed metachromasia significantly more frequently than did FA with a D/W ratio <0.7 (1/6) (Fisher's exact test, P < 0.029). Among eight FA cases confirmed by histology, M-FA cases (6/6) demonstrated metachromasia significantly more frequently than non-M-FA cases (0/2) (P < 0.036). M-FA cytologically exhibits marked metachromasia on Giemsa staining. Combining cytological examination and understanding the clinical features of M-FA may allow us to choose cytological examination as a first-line diagnostic method for tumor-forming lesions.

"High-grade" central acellular carcinoma and matrix-producing carcinoma of the breast: correlation between ultrasonographic findings and pathological features.

High-grade carcinoma with a large central acellular zone (central acellular carcinoma, CAC) and matrixproducing carcinoma (MPC) are aggressive tumors that both have a central myxomatous acellular zone. Their characteristic morphology may be useful in diagnostic imaging. Ultrasonographic findings based on the Breast Imaging Recording and Data System (BI-RADS) and detailed histological features were evaluated in 11 cases of CAC and 2 cases of MPC to characterize their features. Safranin-O staining was undertaken for the evaluation of central acellular zones in these tumors. Overall, ultrasonography demonstrated heterogeneous hyperechoic lesions in the center of the hypoechoic mass. Posterior echo enhancement was observed in all but 1 case. One case was classified as malignant and the others as "borderline." Histologically, cancer tissue was located in the periphery of the tumor with a ring-like structure and fewer cellular central areas comprising hyaline cartilage myxoid material such as those stained by safranin-O. The present study showed that the pathological findings of CACs and MPCs accurately reflect the ultrasonographic findings. Tumors that showed hyperechoic areas in the center of the hypoechoic mass, with posterior echo enhancement indicating acellular zones composed by myxochondroid material, and that were also relatively round on ultrasonography may be benign, but evaluation is required to exclude CAC and MPC.

Myxomatous fibroadenoma of the breast: correlation with clinicopathologic and radiologic features.

Fibroadenoma is a frequently encountered benign tumor that must be differentiated from carcinoma. Fibroadenomas often exhibit myxedematous changes (myxomatous fibroadenoma). We focused on myxomatous fibroadenomas and evaluated their diagnostic imaging and clinicopathologic findings. We examined the (1) clinicopathologic findings of myxomatous fibroadenomas out of 113 fibroadenomas among 592 needle biopsy cases and (2) clinical findings of 27 patients with fibroadenoma who underwent surgical resection. One hundred thirteen (19%) of 592 cases were fibroadenoma, of which 45 cases (40%) were myxomatous fibroadenoma. Based on ultrasonography findings, the depth to width ratio was significantly higher in the myxomatous fibroadenoma group (0.79 ± 0.26) compared with the non-myxomatous fibroadenoma group (0.64 ± 0.26) (P < .01). Forty-two patients were subjected to needle biopsy to differentiate fibroadenoma from carcinomas based on ultrasonography and clinical findings, of which 13 cases (31%) were myxomatous fibroadenoma. These lesions showed a relatively round shape and increased posterior echo enhancement with internal hyperechogenicity on ultrasonography. Among 17 resected cases suspected of malignancy that showed rapid growth and/or size greater than 3 cm, 16 cases were myxomatous fibroadenoma. Tumors showing rapid growth and a relatively large size, a high depth to width ratio, a relatively round shape, and posterior echo enhancement with internal hyperechogenicity on ultrasonography require differentiation from (mucinous) carcinoma but are histologically more likely to be myxomatous fibroadenoma. Understanding the histologic features and combining the ultrasonography findings of myxomatous fibroadenomas may permit reduction in the number of unnecessary needle biopsies for tumor-forming lesions.

Recurrence of invasive micropapillary carcinoma of the breast with different ultrasound features according to lesion site: case report.

Invasive micropapillary carcinoma (IMPC) of the breast is a distinct variant of breast cancer. Extensive lymphatic penetration, lymph node metastasis, and local recurrence are seen at a relatively high frequency. On ultrasound (US) findings, IMPC has been reported to be an irregular or lobulated mass with hypoechoic internal areas, but as yet there is no consensus regarding typical findings. A 52-year-old female noticed a mass less than 3 cm in diameter in her left upper breast. US findings indicated an irregularly shaped, hypoechoic tumor with indistinct margins. The diagnosis according to fine-needle aspiration cytology was invasive ductal carcinoma. She underwent lymph node dissection with mastectomy of the left breast. Histological examination revealed mixed-type IMPC. Three years and three months after surgery, IMPC recurred under the skin of the surgical scar. US findings indicated a hyperechoic tumor in this region. Eight months after further surgery, a tumor in the anterior chest wall was observed. US findings indicated an oval hypoechoic tumor with posterior acoustic enhancement. US findings differed between primary and recurrent IMPC because of differences in the occupancy and distribution of IMPC. We describe here a comparison between US and histological findings, as well as differences in IMPC between primary, secondary and tertiary sites.