Dedifferentiation in Breast Metastasis of Endometrial Carcinoma: A Diagnostic Dilemma.

Most breast tumors are primary to this site; breast metastasis of endometrial origin is extremely rare. Low-grade endometrioid endometrial carcinomas can undergo dedifferentiation to undifferentiated carcinoma but such transformation at a metastatic site has been reported previously in only 2 cases. We report a case of dedifferentiation occurring in an isolated solitary breast metastasis of a low-grade endometrioid endometrial carcinoma. A 64-yr-old woman presented with a breast mass 2 yr after initial diagnosis of a grade 1 FIGO stage IIIA endometrioid endometrial carcinoma. Ultrasound guided biopsy of the breast mass showed a grade 1 endometrioid carcinoma which was diffusely estrogen receptor and PAX8-positive, consistent with metastasis from the previous endometrial carcinoma. The tumor initially responded to Letrozole therapy but then abruptly increased in size. Mastectomy revealed a poorly differentiated malignant tumor with morphology and immunophenotype (including loss of ARID1A and ARID1B immunoreactivity) consistent with undifferentiated endometrial carcinoma with no residual low-grade component. Awareness of the phenomenon of dedifferentiation of endometrial carcinoma in a metastatic site is important to avoid misdiagnosis as a primary breast cancer or metastasis from another primary site.

Unusual Manifestations of Vulval Paget Disease.

Vulval extramammary Paget disease (vEMPD) is an uncommon epithelial malignancy that may arise within the vulva (primary vEMPD) or represent vulval skin involvement by a noncutaneous carcinoma (secondary vEMPD). Primary vEMPD is most often an in situ carcinoma arising within the epidermis but may be associated with dermal invasion (invasive vEMPD) or represent intraepidermal spread of an adenocarcinoma originating in vulval skin adnexa or anogenital mammary-like glands. The latter, termed mammary gland-like adenocarcinoma (MGLA), exhibits morphologic, immunohistochemical, and molecular features of various breast carcinomas but, as far as we are aware, the metaplastic variant of MGLA has not been reported on the vulva. We report 2 cases of metaplastic MGLA of the vulva with associated Paget disease and postulate that some cases of vulval MGLA may arise from Paget disease rather than originating in mammary-like glands. We also report a unique case of secondary vEMPD resulting from spread of urothelial carcinoma in situ that subsequently progressed to invasive urothelial carcinoma within the vulva.

Primary Angiosarcoma of the Cervix: Case Report of a Rare Lesion.

Angiosarcomas of the female genital tract are rare and primary angiosarcoma of the cervix is extremely rare with only one prior case report. We report a case of a primary cervical angiosarcoma in a 43-yr-old woman who presented with heavy vaginal bleeding. Cervical biopsy and subsequent radical hysterectomy showed a malignant vascular tumor which was composed of spindled and epithelioid cells and formed abortive vascular channels. Immunohistochemically, the tumor cells were diffusely positive for CD31, CD34, ERG, and cyclin D1 and focally positive for D2-40. A reverse transcription polymerase chain reaction test for YWHAE-NUTM2 genetic fusion was negative excluding a YWHAE-translocated high-grade endometrial stromal sarcoma. The tumor formed a 5 cm mass within the cervix with microscopic involvement of the endometrium, superficial myometrium, and vagina. Metastatic microscopic tumor deposits were present in both ovaries, left fallopian tube, one paracervical lymph node, and one pelvic lymph node. In reporting this unusual case we discuss the differential diagnosis.

The clinical significance of lymph node micrometastasis in stage I and stage II colorectal cancer.

AIM: Recent advances in immunohistochemical techniques have made it possible to identify micrometastasis using antibodies to cytokeratins (CK). The aim of the study was to determine the prevalence and prognostic significance of immunohistochemically detected micrometastasis (IHM) in patients with localised colorectal cancer (CRC) (Dukes' A and B). A further aim was to study the prognostic role of histopathological factors such as vascular invasion. METHODS: The original histology of 168 consecutive patients with Dukes' A or B tumours who had undergone curative resection was reviewed. Immunohistochemical staining was performed using CK antibodies, AE1/AE3 and MNF116 on all (n=898) lymph nodes. Survival analysis was performed on 105 cases that had been followed up until death or for at least 5 years. RESULTS: IHM were detected in 17.3% of lymph nodes analysed. Adverse outcome (death/local recurrence) was recorded in 8/49 (16%) patients with IHD-positive nodes and in 10/56 (18%) patients negative for IHM. IHM was not associated with adverse outcome on either univariate (p=0.540) or multivariate analyses (p=0.673). There was no correlation of IHM with age, gender, site, size and grade of tumour, depth of tumour invasion or perineural and vascular invasion. Vascular invasion was the only independent prognostic factor identified. DISCUSSION: We have shown that isolated CK-positive epithelioid cells are commonly found in morphologically benign pericolic lymph nodes of patients with localised (Dukes' A or B) CRC. These cells may represent occult micrometastasis but are not clinically significant. Vascular invasion identifies patients with localised CRC likely to develop recurrences or die of disease.

False-negative core needle biopsies of the breast: an analysis of clinical, radiologic, and pathologic findings in 27 concecutive cases of missed breast cancer.

BACKGROUND: A benign diagnosis in a core needle biopsy (CNBx) of the breast performed for a clinically and/or radiologically suspicious abnormality is often due to a nonrepresentative sample. However, the discordance may not be recognized, resulting in a logistic delay in the diagnosis. METHODS: Twenty-seven false-negative CNBxs were identified in 952 consecutive CNBxs of the breast (653 benign, 266 malignant, and 33 atypical) performed during a 1-year period. Biopsies were analyzed with respect to clinical and radiologic findings, biopsy type, type of malignancy, and interval between the original CNBx and final diagnosis. Four hundred thirty-eight (67%) of the patients with a benign CNBx diagnosis either underwent excision or had a minimum of 1-year follow-up (mean, 35.6 months; median, 36 months). RESULTS: The cancers missed on CNBx included 6 ductal carcinomas in situ, 17 invasive ductal carcinomas, 3 invasive lobular carcinomas, and 1 non-Hodgkin lymphoma. The overall false-negative rate was 9.1%. For palpable lesions, ultrasound-guided CNBx had a lower rate of missed cancer (3.6%) compared with CNBx without image guidance (13.3%). The false-negative rate for vacuum assisted CNBx biopsy was 7.6% (3.3% for the 11-gauge needle, 22.2% for the 14-gauge needle; 5.6% for nonpalpable mass lesions, 8.2% for microcalcifications). In all seven false-negative CNBxs performed by radiologists, the discordance between the radiologic and pathologic findings was promptly recognized due to their standard follow-up protocol. The discordance between the degree of clinical suspicion, radiologic impression, and the pathologic findings was not immediately recognized in 5 of 20 false-negative CNBxs performed by surgeons (4 without radiologic guidance and 1 with ultrasound guidance), resulting in a delay in the diagnosis ranging from 112-336 days. CONCLUSIONS: A false-negative diagnosis of breast carcinoma was found to be more common in CNBx performed without image guidance but occurred to a lesser degree in image-guided biopsies. A delay in diagnosis can be avoided by establishing a standard post-CNBx follow-up protocol.