Care within a veterans hospital: earlier detection of colon cancer.

BACKGROUND: In 1998 the Veterans Administration mandated an externally monitored targeted colon cancer screening rate that was expected to result in earlier cancer detection and improved patient survival. The effectiveness of the protocol was evaluated in a retrospective case series at a tertiary care Veterans Administration Hospital that included all patients with the diagnosis of colon cancer between 1991 and 2003. METHODS: Tumor stage, tumor location, and patient survival data were recorded and compared to National Cancer Data Base (NCDB) benchmarks. RESULTS: The study facility had a greater percentage of early cancers and fewer later stage cancers than the NCDB benchmark. Overall survival was better for the VA cohort compared to NCDB (all-cause 5-year survival: VA, 0.72; NCDB, 0.47. p < or = .001). CONCLUSIONS: The VA facility had a significantly greater percentage of early cancers and fewer stage III or IV cancers compared to a national benchmark and significantly improved survival compared to the national benchmark.

Ectopic prostate: case report of a presacral mass presenting with obstructive symptoms.

We report the unusual case of a 78-year-old man who presented with obstructive bowel symptoms and a 2.5-cm presacral mass. The mass was excised and found on pathologic examination to be ectopic prostate tissue complete with a muscular stroma. Review of the literature revealed a number of case reports describing variably sized fragments of ectopic prostate tissue involving a variety of organs, including spleen, uterine cervix, bowel wall, pericolic fat, anal submucosa, seminal vesicle, testis, and urinary bladder. However, to our knowledge, this case is unique in that it presented as a relatively large, isolated presacral mass causing functional bowel impairment. The ectopic location can be related to the normal embryonic development of the prostate, rectum, and bladder.

Cytokeratin staining in Merkel cell carcinoma: an immunohistochemical study of cytokeratins 5/6, 7, 17, and 20.

Merkel cell carcinoma is an aggressive cutaneous neoplasm with neuroendocrine differentiation that carries a poor prognosis. Its homogeneous morphology is easily confused with lymphoma, leukemia, metastatic small cell carcinoma, and poorly differentiated cutaneous malignancies. Histopathologic diagnosis frequently requires support by immunohistochemistry. The authors investigated cytokeratins (CKs) 5/6, 7, 17, and 20 staining in paraffin sections of 26 Merkel cell carcinomas to expand the knowledge of the CK staining profile of this entity. Reactivity with anti-CK 20 was demonstrated in 23 of 26 Merkel cell carcinomas (88%). All three CK 20-negative tumors showed punctate staining with anti-keratin CAM5.2. Six of 26 tumors (23%) were positive for CK 7, a finding not previously reported. The staining patterns for both CKs 20 and 7 ranged from punctate (perinuclear) to localized (confined to half of the cytoplasm) to diffuse. Punctate CK 20 staining was seen in 17 of 26 cases but was the predominant pattern in only 10 cases. Antibodies to CKs 5/6 and 17 were each negative in the 13 cases for which these stains were performed. Both the positive and negative elements of the CK profile of this distinctive neoplasm provide additional useful diagnostic information for the differential diagnosis between Merkel cell carcinoma and other carcinomas that may simulate it. The authors note that the classically described perinuclear dotlike keratin staining pattern is not universally seen with CK 20 and that CK 7 staining may be seen in a subset of Merkel cell carcinomas.

Spindle cell lipoma of the foot and the application of CD34 immunohistochemistry to atypical lipomatous tumors in unusual locations.

Spindle cell lipoma demonstrates a distinctive histologic appearance and characteristic clinical presentation. We recently observed two cases of solitary subcutaneous neoplasm of the foot with histologic features of spindle cell lipoma that in one case includes a minor component of the overlapping tumor, pleomorphic lipoma. Because the foot is an unusual location for these neoplasms, immunoperoxidase and cytogenetic studies were performed. In both cases, staining was strongly positive for CD34 and negative for smooth muscle actin. Cytogenetic studies from the tumor with a pleomorphic component revealed features consistent with a lipomatous neoplasm, but are otherwise diagnostically nonspecific. An analysis of the literature reveals that although CD34 immunoreactivity is characteristic of spindle cell lipoma and helps exclude nonlipomatous neoplasms, it does not clearly eliminate other well-differentiated lipomatous tumors. Accordingly, without the aid of classic tumor location, the diagnosis of the spindle cell/pleomorphic lipoma group relies primarily on histologic features, with supportive but not definitive information provided by immunoperoxidase and cytogenetic studies. Obscuring this issue, however, are the imprecise histologic distinction between these tumors and those of the atypical lipoma/atypical lipomatous tumor/ well-differentiated liposarcoma group and the nomenclature controversy that surrounds the latter group of neoplasms. Despite these obstacles, both groups of well-differentiated lipomatous tumors are clinically benign when subcutaneously located.

A critical examination of the immunophenotype of pulmonary sclerosing hemangioma.

The authors studied a series of 21 cases of pulmonary sclerosing hemangioma (SH) to address conflicting and unconfirmed reports of immunohistologic evidence of differentiation that have been made in the literature. They found the lesional cells of SH to be epithelial membrane antigen (EMA) positive (21 of 21 cases), to be keratin positive only infrequently and focally (six of 21), and to be nonreactive for carcinoembryonic antigen, S-100, smooth muscle actin, and CD34. Faint nuclear staining was seen for estrogen receptors, whereas progesterone receptors were expressed strongly in 17 cases. Neuroendocrine markers (chromogranin A, adrenocorticotrophic hormone, human growth hormone, and calcitonin) were negative uniformly on the lesional cells except for one case in which rare chromogranin-positive cells were present and another case in which rare human growth hormone-positive cells were seen. In contrast to the general EMA-positive, keratin-negative phenotype of the lesional cells, the cells lining the papillae or air spaces within the SH were typically positive for both markers. The following other lesions were identified in the cases studied: carcinoid tumorlets (n = 2), a neuroendocrine body (n = 1), and multiple meningothelial-like nodules (n = 1). All were clearly separable from the SH on morphologic grounds. The authors interpreted these to be chance occurrences of unrelated lesions. Recognition of the phenotype of SH as EMA positive, keratin weak to negative, and negative for S-100, smooth muscle actin, and neuroendocrine markers is notable in its differential diagnosis from other lesions. This phenotype does not suggest a precise lineage or type of differentiation for SH.

Utility of paraffin section immunohistochemistry for C-KIT (CD117) in the differential diagnosis of systemic mast cell disease involving the bone marrow.

Systemic mast cell disease is characterized by an abnormal infiltration of mast cells involving several parenchymal organs and the bone marrow. Its spectrum of clinical and histologic presentation is highly variable and is not necessarily correlated with prognosis. Mast cell disorders presenting as atypical infiltrates in the bone marrow may simulate or be associated with other hematolymphoid malignancies, from which they must be distinguished. The paucity of reliable histochemical and immunohistochemical markers for the detection of mast cells in paraffin sections further confounds this diagnosis. The authors have employed immunohistochemistry for the C-KIT encoded tyrosine kinase receptor protein, CD117, for detection of mast cells on paraffin sections of 89 bone marrow specimens including systemic mast cell disease and other disorders. CD117 staining was found in all cases of mast cell disorders (seven of seven), and in one case of chronic myelogenous leukemia in blast crisis. None of the other myeloid disorders tested (0 of 16), or any of the cases of Hodgkin's disease (0 of 12), B-cell lymphomas (0 of 32), T-cell lymphomas (0 of 3), or histiocytic proliferations (0 of 3) showed staining for CD117. CD117 expression is effective in the separation of mast cell disease from disorders that may simulate it histologically.

Immunoblot analysis of CD34 expression in histologically diverse neoplasms.

CD34 is a heavily glycosylated transmembrane protein of approximately 110 kd whose function is essentially uncharacterized. First identified in a myeloid leukemia cell line, immunohistological reactivity with anti-CD34 antibodies is also encountered in a histologically diverse subset of nonhematolymphoid neoplasms including angiosarcoma, solitary fibrous tumors, epithelioid sarcomas, spindle cell lipomas, dermatofibrosarcoma protuberans, and myofibroblastomas. Immunohistological reactivity for CD34 in hematopoietic stem cells and endothelial cells has been shown to correspond to the expression of the CD34 protein. With the exception of gastrointestinal stromal tumors, CD34 protein expression has not been investigated in other CD34 immunohistologically reactive nonhematolymphoid neoplasms. We undertook this study to examine whether the observed reactivity for anti-CD34 antibodies in apparently unrelated tumors is due to the expression of the same protein or whether shared epitopes elaborated by other proteins could account for this reactivity. Immunoblot analyses with anti-CD34 antibodies of six different CD34 immunohistologically reactive lesions show the same approximately 110-kd molecular weight protein. In addition, two cases of dermatofibrosarcoma protuberans show double bands at approximately 110 kd. Laser-capture microdissection of CD34 immunohistologically reactive epithelioid sarcoma and nonreactive epidermal cells illustrates that this reactivity is specific to tumor cells. These results show that the observed immunohistological reactivity with anti-CD34 antibodies is due to the expression of the CD34 protein and not to shared epitopes on unrelated proteins.

Basal cell carcinoma with tumor epithelial and stromal giant cells: a variant of pleomorphic basal cell carcinoma.

A case of basal cell carcinoma with giant cells of the central epithelial and surrounding stromal components is presented. The lesion was an 8-mm dome-shaped papule on the ear of a 66-year-old man. The giant cells of the epithelial component shared the immunophenotype of the more typical cells of the basal cell carcinoma (keratin, smooth muscle actin, and bcl-2 positive), whereas the stromal giant cells were positive only for bcl-2. This case represents a peculiar variant of pleomorphic basal cell carcinoma, the significance of which is unknown.

Inhibin and CD99 (MIC2) expression in uterine stromal neoplasms with sex-cord-like elements.

Uterine mesenchymal neoplasms with sex-cord-like elements are designated as endometrial stromal tumor with sex-cord-like elements (ESTSCLE) or uterine tumor resembling ovarian sex-cord tumor (UTROSCT), depending on the extent of sex-cord-like differentiation. Occasionally, sex-cord elements similar to those in ESTSCLE and UTROSCT occur in uterine adenosarcomas. To determine whether the sex-cord-like elements in these tumors show immunohistological evidence of sex-cord differentiation, we studied a series of uterine neoplasms for expression of inhibin, a peptide hormone expressed by normal ovarian granulosa cells and ovarian sex-cord neoplasms, and CD99, a protein also expressed by granulosa cells, Sertoli cells, and some ovarian sex-cord tumors. Thirty uterine mesenchymal neoplasms (five epithelioid or plexiform smooth muscle tumors, three endometrial stromal tumors, two mixed endometrial stromal and smooth muscle tumors, 10 ESTSCLE, five UTROSCT, and five miscellaneous stromal processes) and five epithelial neoplasms were evaluated for expression of CD99 (clone 12E7) and inhibin (clone R1) in formalin-fixed, paraffin-embedded tissue. Three of 10 (30%) ESTSCLE and five of five (100%) UTROSCT were inhibin and CD99 immunoreactive. Inhibin staining was confined to the areas with sex-cord-like differentiation, and staining was generally much stronger and more extensive in areas featuring prominent foam cells. There were no differences in the degree or intensity of staining for inhibin in premenopausal and postmenopausal women. CD99 expression tended to correlate with inhibin and was typically confined to similar cell types in the individual neoplasms. Weak CD99 immunoreactivity was seen in one additional epithelioid smooth muscle tumor, whereas all other mesenchymal and epithelial neoplasms studied for inhibin and CD99 were negative. These results provide further immunohistological support for true sex-cord differentiation within uterine mesenchymal proliferations and suggest that the degree of sex-cord differentiation may correlate with the expression of these markers.

Intraepidermal cytokeratin 7 expression is not restricted to Paget cells but is also seen in Toker cells and Merkel cells.

Histologically, extramammary Paget's disease and mammary Paget's disease (MPD) are characterized by large atypical cells distributed throughout the epidermis. Although classic examples of these disorders are easily diagnosed on morphologic grounds, some cases may cause differential diagnostic problems. Immunohistology with a wide variety of antibodies has been used as an aid for the identification of Paget cells, for their distinction from other entities, and for investigation of the origin or nature of the disorder. Recently, cytokeratin 7 has been proposed as a specific and 100% sensitive marker for Paget's disease. We studied 22 cases of mammary Paget's disease and 22 cases of extramammary Paget's disease with and without an underlying malignancy for their reactivity with monoclonal antibodies to cytokeratin 7 (CK7) and cytokeratin 20 (CK20). Our studies show that anti-CK7 is an effective but not 100% sensitive marker for Paget cells, staining 21 of 22 cases of mammary Paget's disease and 19 of 22 cases of extramammary Paget's disease, whereas CK20 stained 0 of 17 cases of mammary Paget's disease and 6 of 19 cases of extramammary Paget's disease. We also demonstrate that CK7, but not CK20, highlights intraepidermal clear cells with bland nuclear features (Toker cells) that have been reported in 11% of normal nipples. By using CK7 as a marker, however, we were able to identify Toker cells in most of the nipples we studied: 8 of 15 nipples from mastectomy patients without Paget's disease, and 15 of 18 autopsy cases (both male and female) with normal breasts and nipples. It also permitted us to perform more extensive phenotyping on them, showing that Toker cells share similar antigens with Paget cells and with cells lining the underlying normal lactiferous ducts. In 7 of 15 cases containing CK20-positive Merkel cells, CK7 was also seen to stain Merkel cells. In infrequent cases, Toker cells or Merkel cells may be so numerous focally that a CK7 stain may raise the possibility of involvement of the nipple by Paget's disease. An awareness of the CK7 reactivity of Toker cells and Merkel cells as well as attention to the cytologic features of the case should avoid this problem.

The differential diagnosis of pagetoid cells in the epidermis.

In addition to Paget's disease, a heterogeneous group of processes with diverse histogeneses can give rise to intraepidermal pagetoid cells. These diseases share as their common denominator the presence of discrete non-Malpighian or abnormal Malpighian cells occurring singly or in nests within the epidermis. Either Pagetoid cells can represent the only histologic change, as in pagetoid squamous cell carcinoma in situ or superficial spreading malignant melanoma in situ, or they can be an expression of an associated dermal or internal malignancy, as in sebaceous carcinoma or breast carcinoma. The histologic appearance of the pagetoid cells in these diverse disorders can be quite similar, rendering the differential diagnosis difficult. A review of the entities that enter into the differential diagnosis of intraepidermal pagetoid cells is presented, emphasizing their distinguishing histologic and immunophenotypic features and differential diagnosis.

Menetrier's disease: report of a transient case associated with chylous ascites.

We present a case of transient Menetrier's disease (MD) that was associated with chylous ascites. Using immunohistochemistry, we studied the expression of transforming growth factor alpha in this patient's gastric mucosa biopsy over time; a growth factor that has previously been shown to play an active role in the pathogenesis of MD. Excessive expression and altered localization of transforming growth factor alpha was observed while the patient had active disease with return to the normal pattern after resolution of the disease. This case is the first one reported of transient MD associated with chylous ascites; it lends further credible evidence to the concept that altered transforming growth factor alpha expression may play an important role in the pathogenesis of MD.

Value of inhibin in the identification of granulosa cell tumors of the ovary.

Inhibins are peptide hormones that participate in the regulation of the pituitary-gonadal feedback system and are selectively expressed by cells of sex cord-stromal derivation. To determine the efficacy of this marker for distinguishing granulosa cell tumors, 134 primary and metastatic lesions of the ovary were evaluated for expression of the alpha-subunit of inhibin in routinely processed formalin-fixed, paraffin-embedded tissue. A variety of sex cord-stromal tumors (SCST), including 35 adult and juvenile granulosa cell tumors, 14 fibroma-thecomas, and 18 other sex cord-stromal proliferations, were studied. In addition, 33 surface epithelial neoplasms, 12 germ cell tumors, 11 metastases, and 11 miscellaneous ovarian neoplastic proliferations were evaluated. Among the non-granulosa cell neoplasms, special emphasis was placed on primary neoplasms and metastases that histologically simulated granulosa cell tumors. Thirty-three of 35 (94%) granulosa cell tumors were immunoreactive compared with 2 of 12 (17%) primary ovarian endometrioid tumors, one of nine (11%) primary ovarian transitional cell (Brenner) proliferations, and 3 of 17 (18%) other primary and metastatic poorly differentiated (undifferentiated) carcinomas. In 31 of the 35 granulosa cell tumors, inhibin staining was of moderate to strong intensity or was present in at least half of the constituent cells, whereas only 2 of 33 primary surface epithelial neoplasms fulfilled the same criteria, showing weak staining of 70% to 80% of the cells. In contrast, 10 of 14 (71%) ovarian fibroma-thecomas and 17 of 18 (94%) other sex cord-stromal proliferations were positive for inhibin. Nonneoplastic luteinized stromal cells stained for inhibin in 29 of 85 cases in which they could be evaluated. The results of this study show that although it is not completely specific and cannot reliably distinguish granulosa cell tumors from fibroma-thecomas or other ovarian sex cord-stromal proliferations, inhibin can be used to help distinguish sex cord-stromal neoplasms from most primary and metastatic non-SCST. Caution should be exercised in the interpretation of inhibin-positive cells, because a wide variety of primary and metastatic ovarian tumors may contain significant numbers of positively staining luteinized cells.

Desmoplastic and spindle-cell malignant melanoma. An immunohistochemical study.

The clinical, histologic, and immunohistologic features of 22 desmoplastic melanomas (DMM), 10 mixed desmoplastic and spindle-cell melanomas (DMM/SMM), and two cellular spindle-cell melanomas (SMM) were studied. Patients ranged in age from 35 to 91 years (mean, 67) and included 23 men and 11 women. Seventeen cases occurred in sun-damaged skin of the head and neck. 11 were on the extremities, and six on the trunk. Except for two cases, all were Clark's level IV or V. Twenty-two (65%) cases were associated with a recognizable overlying pigmented lesion. Thirty of 32 (94%) DMM and DMM/SMM were clearly positive for S100. S100 staining was limited to < 5% of the spindle cells in two DMM/SMM. All DMM were negative when stained with HMB45. Three DMM/ SMM were immunoreactive with HMB45, as were both SMM. CD68 staining was limited to < 5% of the spindle cells in two of 32 DMM and DMM/SMM and 20% of the cells in one of two SMM. Nine (32%) DMM and DMM/SMM contained significant numbers of spindle cells immunoreactive for SMA but not desmin. In five cases, the number of actin-positive spindle cells. Two color stains for SMA and S100 demonstrated that these smooth-muscle actin positive cells constituted a separate spindle-cell population, consistent with reactive myofibroblasts. This study indicates that the immunohistologic features of desmoplastic melanoma differ from those of conventional melanoma. If a problematic spindle-cell skin lesion is a suspected melanocytic process, HMB45 is unlikely to provide confirmatory (or exclusionary) evidence for the diagnosis of DMM. Similarly, because of the variability in S100 expression in this neoplasm, the absence of S100 staining should not be relied on too heavily to exclude DMM if the clinical and histologic features favor that diagnosis. Caution should be exercised in the interpretation of numerous actin-positive spindle cells in isolation of additional confirmatory or exclusionary data as desmoplastic melanomas may contain significant numbers of these cells.

Atypical polypoid adenomyofibroma (APA) versus well-differentiated endometrial carcinoma with prominent stromal matrix: an immunohistochemical study.

It can be extremely difficult in some cases to distinguish atypical polypoid adenomyomas (APAs) from invasive adenocarcinoma in an endometrial curettage or biopsy specimen. In order to determine if immunophenotypic features can be exploited to differentiate between these two entities in problematic cases, a series of APAs and myoinvasive well-differentiated endometrial carcinomas (WDCAs) were studied with a panel of standard immunohistochemical markers. All 23 APAs had stromal smooth muscle actin (SMA) reactivity, 12 of 23 had variable degrees of stromal desmin reactivity, and nine of 22 had CD34-positive stromal cells. All epithelial components of the APAs were cytokeratin (AE1 and CAM5.2) positive, whereas 22 of 23 were positive for estrogen receptor (ER) and progesterone receptor (PR). Among the 10 myoinvasive WDCAs, all contained at least some SMA-positive stromal cells, seven of 10 desmin-positive stromal cells, and four of eight CD34-positive stromal cells. All carcinomas studied demonstrated CAM5.2 and PR-positive epithelia; nine of 10 were ER positive. We conclude that the immunophenotype of APAs does not differ significantly from well-differentiated endometrial adenocarcinoma and that immunophenotyping is of little value in distinguishing APA from carcinoma. Because the stroma in APAs histologically and immunophenotypically more closely resembles a hybrid myofibromatous stroma, we prefer to refer to these lesions with the modified designation "atypical polypoid adenomyofibroma," although "APA" may be retained for clinical use.

Transitional cell neoplasms of the ovary and urinary bladder: a comparative immunohistochemical analysis.

Walthard cell nests, the Brenner tumor (benign, proliferating, low malignant potential, and malignant), and primary ovarian transitional cell carcinoma are considered to be primary female genital tract proliferations of transitional-type (urothelial) epithelium on conventional light microscopic grounds. In order to further investigate the similarities (or dissimilarities) of proliferations of female genital tract transitional epithelium and urothelium, we compared transitional cell proliferations (TCPs) of the female genital tract (n = 25) and urinary bladder (n = 15) using antibodies to carcinoembryonic antigen (CEA; clone 0062), carbohydrate determinant 19-9 (CA19-9; clone 1116-NS-19-9), cytokeratin 7 (CK-7; clone OV-TL 12/30), and cytokeratin 20 (CK-20; clone Ks 20.8), four monoclonal antibodies that have been shown to stain transitional cell urothelial proliferations. Both groups of tumors exhibited significant staining for CEA, CA19-9, and CK-7, and the difference in numbers of cases staining was not significant. CA19-9 was present in 15 of 25 female genital tract TCPs as compared with 12 of 15 bladder TCPs; CEA was present in 17 of 25 female genital tract TCPs and nine of 15 comparable bladder TCPs. CK-7 was present in all cases studied with the exception of one Walthard cell nest and a malignant Brenner tumor that was not immunoreactive with the other antibodies tested. In contrast, 13 of 15 bladder TCPs were CK-20 positive, whereas only one of 25 female genital tract TCPs was positive (< 5% of cells). Walthard cell nests and benign Brenner tumors were more likely to be CA19-9 positive than were Brenner tumors of low malignant potential, malignant Brenner tumors, and primary transitional cell carcinoma of the ovary. We conclude that despite their apparent morphologic and immunologic similarity to TCPs of the urinary bladder (particularly at the histologically low-grade end of the transitional cells spectrum), Walthard cell nests and ovarian Brenner tumors constitute an immunophenotypically distinct form of TCP.

Atypical polypoid adenomyofibromas (atypical polypoid adenomyomas) of the uterus. A clinicopathologic study of 55 cases.

We present the clinicopathological and immunohistochemical features of 55 atypical polypoid adenomyofibromas, a definitional expansion of an entity previously reported as "atypical polypoid adenomyoma" (APA) of the uterus. Patients ranged in age from 25 to 73 (mean, 39.9) years. All but two of the patients were premenopausal, and 14 were undergoing evaluation for infertility. Histologically, the lesions featured a biphasic proliferation of architecturally complex and cytologically atypical endometrial glands within a myofibromatous stroma. The histologic pattern ranged from widely separated and loosely clustered irregular but branched glands embedded in broad zones of cellular myofibromatous stroma to those possessing crowded, markedly complex, branching glands separated by sparse intersecting fascicles of fibromuscular tissue. The stroma in all cases was actin or desmin positive or both. Morular/squamous metaplasia was present in all but two cases and florid in most. All cases exhibited architecturally complex glands, and in 25 cases the architectural complexity was indistinguishable from that of well-differentiated endometrial adenocarcinoma, as we have defined it; that is, they had a high architectural index. Twenty-nine patients were initially treated with polypectomy or curettage followed by hormonal therapy; persistent or recurrent APA developed in 45% of the patients in this group (33% with low architectural index vs. 60% with high architectural index). Five patients had successful pregnancies despite persistent disease. Superficial myoinvasion was identified in the hysterectomy specimen in two of 12 APAs with a high architectural index but not in 21 APAs with a low architectural index. All patients are alive and well 1 to 112 months after diagnosis (mean, 25.2 months). On the basis of this study, we propose that APAs with markedly complex glands (high architectural index) be designated "atypical polypoid adenomyofibromas of low malignant potential" (APA-LMP) to emphasize the potential risk for myometrial invasion. A treatment program featuring local excision accompanied by close follow-up is warranted for APA despite the presence of recurrent or persistent disease. Patients with APA-LMP may also, in selected cases, be managed with less than hysterectomy, although (as with the usual well-differentiated carcinoma) there is a small but definite risk associated with this approach.

Esophageal submucosal gland duct adenoma.

An 81-year-old man with a 3-year history of dysphagia underwent endoscopic resection of a 1-cm-diameter distal esophageal mass. Examination revealed a submucosal neoplasm with a circumscribed growth pattern composed of tubules, cysts, and papillae in association with a marked interstitial lymphoid infiltrate. The cyst lumens and papillae were lined by two to six layers of cytologically bland cuboidal to columnar cells with rare mitotic figures. The basal layer of cells was uniformly positive for smooth-muscle actin. Mucin-positive intracytoplasmic lumens were focally present, but cytoplasmic mucin was not seen. There was no evidence of Barrett's metaplastic epithelium. These features are similar to those in two, possibly three, previously reported cases of esophageal adenomas and bear a resemblance to sialadenoma papilliferum, a rare neoplasm of the minor salivary glands. Their clinicopathologic and immunohistologic features suggest that these neoplasms derive from the submucosal gland ducts. Comparison with the previously reported cases indicates that although the proportions of the various components (tubules, cysts, and papillae) may vary, all cases appear to pursue a slowly growing, clinically indolent course with no evidence of recurrence after complete resection.

L-selectin and alpha 4 beta 7 integrin homing receptor pathways mediate peripheral lymphocyte traffic to AKR mouse hyperplastic thymus.

Before the development of thymic lymphoma, AKR mice undergo a striking lymphoid hyperplasia of the thymic medulla. We have previously shown that there is a marked increase in traffic of B and T lymphocytes from the periphery into the preneoplastic, hyperplastic thymuses of these mice, in contrast to the scant traffic of such cells to normal thymuses. The traffic of lymphocytes to lymph nodes and Peyer's patches is controlled in part by the interaction of lymphocyte adhesion molecules called homing receptors with their tissue-selective endothelial ligands known as vascular addressins. We have investigated the roles of homing receptors and vascular addressins in the traffic of lymphocytes to the AKR hyperplastic thymus. We demonstrate that development of hyperplasia is accompanied by an increase in the number of thymic medullary blood vessels with high endothelial venule morphology and expression of the peripheral node addressin (PNAd) and the mucosal addressin (MAdCAM-1). In vitro and in vivo functional assays show that the addressin/homing receptor pairs PNAd/L-selectin and MAdCAM-1/alpha 4 beta 7 are involved in lymphocyte traffic to the hyperplastic thymus. These results indicate that molecular adhesion mechanisms involved in tissue-selective migration of lymphocytes to peripheral lymph node and to mucosal lymphoid tissues play a role in the recruitment of B and T lymphocytes to the AKR thymus and thus in the pathogenesis of thymic hyperplasia.