Diane Hamele-Bena

Pulmonary tumor embolism: a review of the literature

Dyspnea in a patient with cancer may have several causes, including infection, thromboembolism, metastases, and therapeutically induced cardiopulmonary disease. Pulmonary tumor embolism is an uncommon cause. Occlusion of the pulmonary microvasculature by tumor cells and associated thrombi can produce a subacute and progressive clinical picture that resembles thromboembolic disease. Unfortunately, microscopic tumor embolism is recognized rarely before death because of difficulty in establishing the diagnosis. We provide a review of the literature about the evaluation and diagnosis of this rare clinical entity.

Expression of PAX8 in normal and neoplastic renal tissues: an immunohistochemical study

Cell-lineage-specific transcription factors are a group of regulatory proteins expressed in embryonic, differentiated, or neoplastic cells of the same lineage and represent a valuable repertoire of tissue-specific markers for the diagnosis of human tumors. Together with PAX2, PAX8 is a nephric-lineage transcription factor and is required for the establishment of renal-lineage cells and the formation of the kidney. In contrast to PAX2, little is known about the expression of PAX8 in adult kidney and renal tumors. In this study, we used immunohistochemistry to investigate the expression of PAX8 in adult human kidney and renal epithelial tumors. We report here that PAX8 was detected in renal epithelial cells in all segments of renal tubules from the proximal tubules to the renal papillae and in the parietal cells of Bowmans capsule in the adult kidney. PAX8 was also present in 98% of clear cell renal cell carcinomas (RCCs), 90% of papillary RCCs, and 95% of oncocytomas, similar to PAX2. In addition, PAX8 was found in 82% of chromophobe RCCs, 71% of sarcomatoid components of RCCs, and 100% (2/2) of renal medullary carcinomas. Overall, PAX8 was detected in 85% of metastatic renal tumors. Interestingly, expression of PAX8 was noted in some urothelial cells in the renal pelvis and ureters and ∼23% of urothelial carcinomas of the renal pelvis, but not in the urothelium or urothelial carcinomas of the urinary bladder; this probably underlines the different embryonic origins of urothelial cells in the upper and lower urinary tracts. As shown in this study, PAX8 is widely expressed in normal and neoplastic renal tissues. PAX8 may be a useful additional marker for renal epithelial tumors; however, its specificity and sensitivity await further investigation.

Mammary mucocele-like lesions benign and malignant

In 1986 mucocele-like lesions (MLL) were described as benign tumors; subsequent reports identified MLL associated with ductal hyperplasia or carcinoma (CA). To characterize MLL further, we studied 53 lesions from 49 patients, in whom 25 MLL were benign and 28 were malignant (14 in situ, 14 invasive). Two had bilateral benign MLL, and two had bilateral MLL with CA. Patients ranged in age from 24 to 79 years (mean, 48 years). There were no appreciable differences in age, tumor size, or laterality between patients with benign or malignant MLL, although MLL with CA had coarse calcifications more often than benign MLL and were more likely to be detected mammographically. Intraductal carcinoma was micropapillary or cribriform, and invasive carcinoma was usually mucinous. Fewer of the benign lesions were estrogen and progesterone receptor positive. HER2/neu positivity was more common in MLL with CA. Known treatment was as follows: for benign MLL, excisional biopsy was done in 22 patients (one with axillary dissection) and total mastectomy in one patient; for MLL with CA, excisional biopsy was done in 17 patients, biopsy followed by wider excision in four patients (three of whom had axillary dissection), and mastectomy and axillary dissection in five patients (one also had radiotherapy). Follow-up ranged from less than a 1 year to 15 years (mean and median, 3.7 years). Two patients had recurrences in the breast (one benign MLL and one MLL with CA). At the time of this report, all were alive without evidence of disease. We conclude that MLL with CA is a low-grade neoplasm with few clinical differences from benign MLL except for more prominent calcifications, leading to mammographic detection. Excisional biopsy is recommended for benign MLL. Breast-conserving surgery is appropriate therapy for MLL with CA. Radiotherapy is indicated if CA involves margins or if extensive intraductal carcinoma is present.

Expression of PAX2 in papillary serous carcinoma of the ovary : immunohistochemical evidence of fallopian tube or secondary müllerian system origin?

PAX2 is a urogenital developmental transcription factor expressed in the Wolffian ducts, developing kidneys, and Müllerian ducts during embryonic stage. Its function in renal development is well documented and its clinical application in the diagnosis of lesions of renal origin has been reported recently. However, information on its role in the Müllerian-derived genital tract is sparse. In this study, we investigated the expression of PAX2 in human female genital tract using immunohistochemistry. We demonstrated that PAX2 was expressed specifically in the epithelial cells of fallopian tube, endometrial and endocervical glands, but not in the stromal tissues in these areas. PAX2 was detected in secondary Müllerian structures in the ovary, such as endometriotic and endosalpingiotic glands and rete ovarii, but not in ovarian surface epithelium, surface epithelium-derived inclusion cysts, stroma, or sex-cord-derived structures such as follicles, oocytes, and corpus luteum. In addition, PAX2 was detected in 67% of ovarian papillary serous carcinomas (N=36) but rarely in peritoneal malignant mesotheliomas, with two exceptions (N=54). Interestingly, the two PAX2-positive ‘peritoneal malignant mesotheliomas’ were from female patients and were positive for estrogen receptor. The significance of expression of PAX2 and estrogen receptor in these cases is under investigation. Taken together, we suggest that PAX2 is a novel Müllerian-specific epithelial marker when used in proper clinical settings. Identification of PAX2 in the majority of papillary serous carcinomas of the ovary but not in the ovarian surface epithelium or epithelium-derived inclusion cysts suggests that this malignant epithelial tumor may be directly derived from the primary or secondary Müllerian epithelium in or surrounding the ovary, rather than from the surface epithelium or its derivatives.

Expression of PAX8 in nephrogenic adenoma and clear cell adenocarcinoma of the lower urinary tract: evidence of related histogenesis?

Recent evidence has showed that nephrogenic adenoma is a true “nephrogenic” lesion derived from the proliferation of exfoliated and implanted renal tubular cells in the urinary tract, a process that closely resembles the formation of endometriosis. This new concept has led to the identification of renal transcription factor PAX2 as a diagnostic marker for nephrogenic adenoma. PAX8 is another transcription factor structurally and functionally related to PAX2. Both are cell lineage restricted transcription factors expressed in normal and neoplastic tissues of related origin, including renal tubular cells in both fetal and adult kidneys. In this study, we investigated the expression of PAX8 in nephrogenic adenoma and its mimics. We report here that PAX8 was detected in all nephrogenic adenomas (N=35) and clear cell adenocarcinoma of the lower urinary tract (N=7), but not in prostate adenocarcinoma (N=100), adenocarcinoma (N=9), squamous cell carcinoma (N=5), or urothelial carcinoma (N=48) of the urinary bladder and its variants. PAX8 was neither detected in normal urothelium of the urinary bladder nor in prostate glands and stroma. PAX2 was also detected in 2 of the 7 clear cell adenocarcinomas of the lower urinary tract. We suggest that PAX8 is an additional marker for identifying nephrogenic adenoma. Expression of PAX8 or PAX2 in both nephrogenic adenoma and clear cell adenocarcinoma of the lower urinary tract may indicate a possible related tissue origin for these 2 lesions; both may be derived from proliferating renal tubular cells in the urinary tract. In addition, detection of PAX8 or PAX2 in clear cell adenocarcinoma of the lower urinary tract is helpful in differentiating it from urothelial carcinoma and its variants and adenocarcinomas of the urinary bladder or of the prostate.

Pax8: A marker for carcinoma of Müllerian origin in serous effusions

PAX8 is a nuclear transcription factor with limited expression in normal and neoplastic tissues in a cell lineage‐dependent manner. PAX8 has been detected in embryonic Müllerian ducts, human fallopian tubes, and ovarian carcinomas. However, little is known about its expression in other areas of the female genital tract. In this study, we used immunohistochemistry (IHC) to examine PAX8 expression in the normal uterine corpus and cervix, malignant tumors arising from these sites, and malignant effusions. We reported here that PAX8 was also detected in endometrial epithelial cells and endocervical glands, with a lower expression level in the latter, but not in the stromal cells of these areas. All endometrial carcinomas (N = 52) were positive for PAX8, whereas endocervical adenocarcinomas (N = 5) and uterine leiomyosarcomas (N = 3) were negative for PAX8. PAX8 was detected in 70% (22/31) and 68.8% (11/16) of metastatic carcinomas of the ovary and endometrium in serous effusions, respectively. No PAX8 was detected in carcinomas of nongynecologic origin or noncarcinomas (N = 71) in serous effusions except in one renal‐cell carcinoma and one carcinoma of unknown primary in a woman. In addition, papillary serous carcinomas of the peritoneum (N = 10) were diffusely positive for PAX8, implying a Müllerian origin similar to malignant tumors in the female genital tract. Our findings suggest that PAX8 is an additional IHC marker for carcinomas of Müllerian origin hence we recommend including PAX8 for evaluation of malignant serous effusions in women, especially when tumors of Müllerian origin are in the differential diagnosis. Diagn. Cytopathol. 2011.

Pseudoangiomatous stromal hyperplasia of the breast: sonographic features with histopathologic correlation.

Abstract:  The objective of this study was to evaluate the spectrum of sonographic findings in pseudoangiomatous stromal hyperplasia (PASH) of the breast when it presents as a tumoral mass with pathologic correlation. Breast sonogram studies of 13 patients with 13 pathologically proven PASH lesions were retrospectively reviewed. The morphologic characteristics of the lesions as seen on ultrasound were evaluated and correlated with histopathologic findings. Sonography demonstrated most lesions, 11 of 13, to be hypoechoic in echotexture. One lesion was isoechoic in echotexture, also demonstrating small internal cysts, and one was predominantly hyperechoic. Two of the 11 hypoechoic lesions also demonstrated a complex heterogeneous pattern with a central hypoechoic area and a peripheral echogenic rim. All lesions were oval in shape with the long axis of the lesion parallel to the chest wall. None of the lesions demonstrated posterior acoustic shadowing. PASH lesions of the breast have a varied sonographic appearance. Knowledge of the spectrum of morphologic features shown on sonography can be helpful in the diagnosis of this entity. 

Fine-needle aspiration biopsy findings in marginal zone B cell lymphoma.

Marginal zone B cell lymphomas (MZBCLs) represent a category of non‐Hodgkins lymphoma which may arise in a wide variety of extranodal organs where they are termed low grade B cell lymphomas of mucosa‐associated lymphoid tissue (MALT). MZBCLs may involve primarily lymph nodes and or spleen where they are designated monocytoid B cell lymphoma or splenic marginal zone lymphoma, respectively. Recognition of this category of lymphoma, in particular, extranodal MALT lymphoma, is clinically significant in determining optimal therapy. Although there have been recent case reports describing the cytologic findings in low grade MALT lymphoma in various extranodal organs, this category of lymphoma has not been widely recognized or discussed in the cytology literature. The cytologic findings in seven fine‐needle aspirations and two bronchial washings of histologically confirmed marginal zone lymphoma (five extranodal MALT lymphomas and four nodal marginal zone lymphomas) are described. In all of the cases, the cytologic specimens showed a polymorphous proliferation comprising a predominant population of intermediate sized lymphoid cells with centrocyte‐like or monocytoid features, transformed cells, and variable numbers of plasma cells. These findings, while highly suggestive of MALT lymphoma in extranodal proliferations, may be more difficult to distinguish from reactive conditions in lymph nodes. Diagn. Cytopathol. 1999;20:190–198.

PAX8 and PAX2 immunostaining facilitates the diagnosis of primary epithelial neoplasms of the male genital tract

PAX8 and PAX2 are cell-lineage-specific transcription factors that are essential for the development of Wolffian and Müllerian ducts and have recently emerged as specific diagnostic markers for tumors of renal or Müllerian origin. Little is known about their expression in the Wolffian duct-derived human male genital tract. We report our findings of PAX8 and PAX2 expression in the epithelium of the normal male genital tract and in epithelial tumors derived therefrom using immunohistochemistry (IHC). We found that PAX8 and PAX2 were expressed in the epithelium of the male genital tract from the rete testis to the ejaculatory duct. Rare glands in the prostatic central zone, a tissue of purported Wolffian duct origin, were focally positive for PAX2, but no PAX8 was detected in this area, a finding that may warrant further study. We found diffuse expression of PAX8 and PAX2 in 1 case each of serous cystadenoma of the epididymis, carcinoma of the rete testis, Wolffian adnexal tumor of the seminal vesicle, and endometrioid carcinoma of the seminal vesicle. Neither PAX8 nor PAX2 was detected in the seminiferous tubules and interstitium of the normal testis, nor in Leydig cell tumors (n=6), Sertoli cell tumors (n=2), or 48 of 49 germ cell tumors. One pediatric yolk sac tumor showed focal and weak staining for PAX8. Tumors of mesothelial origin, that is, adenomatoid tumors (n=3) and peritoneal malignant mesotheliomas (n=37) in men, were negative for PAX2 and PAX8. Neither PAX2 nor PAX8 was present in other areas of the prostate. Expression of PAX8 and PAX2 in these primary epithelial neoplasms of the male genital tract is due to their histogenetic relationship with Wolffian or Müllerian ducts. PAX8 and PAX2 IHC may facilitate the diagnosis of these tumors and should be included in the differential diagnostic IHC panel.

Fine-needle aspiration biopsy of primary osteosarcoma of the thyroid: Report of a case and review of the literature

Primary osteosarcoma of the thyroid is an extremely rare tumor, with only 27 well‐documented cases reported in the literature, including only one in the cytology literature. We describe here an additional case with fine‐needle aspiration biopsy findings. A 60‐year‐old woman presented with a 1‐month history of progressive midline neck swelling. CT and ultrasound demonstrated a large thyroid mass with tracheal compression. Fine‐needle aspiration biopsies were performed and showed pleomorphic spindle and epithelioid neoplastic cells, multinucleated giant cells, and scant metachromatic extracellular matrix material. Cell block sections contained minute tissue fragments with neoplastic spindle cells. Immunohistochemical stains showed the tumor cells to be positive for vimentin and negative for cytokeratins, TTF‐1, calcitonin, synatophysin, chromogranin, and S‐100 protein, suggesting a sarcoma; however, the differential diagnosis also included anaplastic thyroid carcinoma and medullary thyroid carcinoma. Tissue biopsy revealed a high‐grade spindle cell neoplasm with osteoid production, consistent with osteosarcoma of the thyroid. The patient developed a large pulmonary embolus and superior vena cava syndrome and no further surgical intervention was performed. She died 5 weeks after the initial diagnosis. Upon retrospective review, the cytologic features resemble osteosarcoma in other areas. Although cytologic features on fine‐needle aspiration biopsy may suggest a diagnosis of this rare entity, definitive diagnosis should be deferred to histologic examination. Diagn. Cytopathol. 2008; 36: 589–594.