D. Garth Perkins

Glomus tumor of the trachea.

Extracutaneous glomus tumors are uncommon and rarely occur in the trachea. We describe a 73-year-old man with a glomus tumor of the trachea who presented with cough, dyspnea, chest pain, and hemoptysis. A curative segmental tracheal resection with primary reconstruction was performed with no recurrence at 6-year follow-up. The clinicopathologic features of this unusual neoplasm are discussed with a review of the literature.

Incidental Prostatic Adenocarcinomas and Putative Premalignant Lesions in TURP Specimens Collected Before and After the Introduction of Prostrate-Specific Antigen Screening

BACKGROUND Since the introduction of prostate-specific antigen (PSA) screening for the detection of prostatic adenocarcinoma (PCA), there has been an increase in the incidence of stage T1c PCA. The purpose of this study was to compare the frequency of incidental PCA found in transurethral resection of prostate (TURP) specimens for a 14-month period during 1989-1990 (before PSA screening was available) with the incidence of PCA for a 32-month period during 1997-1999 (after PSA screening became available). DESIGN Consecutive TURP specimens from the 2 time periods were reviewed to identify incidental PCA, prostatic intraepithelial neoplasia (PIN), and atypical adenomatous hyperplasia (AAH). Cases of TURP for palliative treatment of known advanced PCA were excluded from the study. All TURP specimens were fixed in 10% buffered formalin and were processed according to the same protocol. RESULTS We reviewed 533 and 449 TURP specimens for the time periods 1989-1990 and 1997-1999, respectively. Comparison of the results for these 2 time periods revealed that the combined prevalence of T1a and T1b PCA decreased over time from 12.9% to 8.0% (P =.06) with the introduction of PSA screening. A new group of T1c PCA was established in the post-PSA screening period of 1997-1999. There were no statistically significant differences in the incidences of T1a PCA, PIN, and AAH in TURP specimens for the 2 time periods. CONCLUSION The decreased incidence of T1b PCA in TURP specimens for the 1997-1999 period represents a shift in PCA staging. Some PCAs previously staged as T1b are now staged as T2 carcinomas, as a result of PSA screening and earlier clinical detection. The introduction of PSA screening has had no influence on the incidence of T1a PCA, PIN, or AAH in TURP specimens.

Fine needle aspiration biopsy of epithelioid angiomyolipoma. A case report.

BACKGROUND Epithelioid angiomyolipoma (AMYL) is a variant of angiomyolipoma characterized by sheets of epithelioid cells that may mimic renal cell carcinoma. This is the first report describing the fine needle aspiration biopsy features of this lesion. CASE A 47-year-old man with a history of epithelioid angiomyolipoma of the kidney treated with nephrectomy nine months previously presented with a recurrent retroperitoneal mass and multiple nodular liver lesions. Fine needle aspiration biopsy of one of the liver lesions showed fragments and sheets of noncohesive epithelioid cells with thin cytoplasm, markedly atypical nuclei, and scattered bizarre and multinucleated forms. The epithelioid cells focally expressed HMB-45 and were nonimmunoreactive, with epithelial markers. CONCLUSION Epithelioid AMYL may pose differential diagnostic problems with high grade carcinoma, especially renal cell, hepatocellular and metastatic carcinoma. An awareness of this entity and its characteristic cytologic features and immunoreactivity with HMB-45 is helpful in its identification.

ADENOMATOID TUMOR OF THE GENITAL TRACT : EVIDENCE OF MESENCHYMAL CELL ORIGIN

The objective of this study was to re-examine the histogenesis of adenomatoid tumors. This benign neoplasm is characterized by gland-like structures with a pseudodinfiltrative pattern, usually involving fibromuscular tissue at a certain distance from an overlying surface mesothelium. Twenty cases of adenomatoid tumors and four cases of reactive submesothelial lesions, characterized by marked proliferation of subserosal mesenchymal cells, were reviewed. Nineteen of twenty adenomatoid tumors, including lesions with ill-defined borders, showed no connection with surface mesothelium. At the periphery of small tumors, isolated glands, clusters of epithelioid cells and single epithelioid, and spindled cells showing no connection to adjacent glands or cell clusters were identified. The tumor cells shared features with reactive subserosal stromal cells including an infiltrative pattern and histochemical and immunohistochemical properties. The differences between adenomatoid tumors and reactive submesothelial tissue are quantitative in nature: predominant amount of spindled cells in reactive submesothelial lesions, and predominant amount of gland-like structures in adenomatoid tumors. It is proposed that adenomatoid tumors arise from pluripotent mesenchymal cells that differentiate toward submesothelial cells and eventually mesothelial cells. This differentiation is probably induced by the adjacent submesothelial cells.

Location and Extent of Positive Resection Margins and Ductal Carcinoma in Situ in Lumpectomy Specimens of Ductal Breast Carcinoma Examined with a Microscopic Three-Dimensional View

Abstract: The location of positive margins in lumpectomy specimens for ductal carcinoma could be predicted due to the common pattern of the geographic relationship between the intraductal and invasive carcinomas. To test this hypothesis, 62 lumpectomy specimens for ductal carcinoma of the breast were submitted for this study. The specimens were microscopically examined by serially sectioning them into giant sections in a plane parallel to the chest wall (frontal plane). The margins were identified as proximal (closest to the nipple), distal (opposite to proximal), and peripheral (nonproximal or distal). We found that the location of positive or close margins was proximal in 6 cases, peripheral in 13 cases, and none were found to be distal. Ductal carcinoma in situ (DCIS) was found to be located in the area adjacent to the invasive carcinoma. The invasive carcinoma was located at the periphery of the intraductal carcinoma. All six specimens with invasive carcinoma without DCIS had free margins. Nine of 16 specimens (56%) with extensive intraductal carcinoma (EIC) component and 7 of 40 (18%) with DCIS but negative EIC contained positive or close margins involved by DCIS. One case with multifocal invasive carcinoma measuring 3.5 cm in diameter and with DCIS but EIC negative had margins involved by both DCIS and invasive carcinoma. In conclusion, in ductal carcinoma, invasive carcinoma arose at the peripheral areas of the DCIS. DCIS tends to spread toward the nipple and the peripheral margins of the resected specimens. Incomplete excision of the ductal carcinoma and the wide positive margins are most likely caused by the failure to estimate the extent and location of DCIS. 

Differentiated thyroid carcinomas with vascular invasion: a comparative study of follicular, Hürthle cell and papillary thyroid carcinoma

Aim: Non‐medullary thyroid carcinomas arise from follicular cells. The purpose of this study is to correlate clinical and pathological properties of these tumours with the rate of distant metastasis from a series of thyroid tumours excised at one institution. Methods: A total of 311 non‐medullary thyroid tumours were identified and divided into: 29 follicular carcinoma (FC), 12 Hürthle cell carcinoma (HC), 13 Hürthle cell papillary thyroid carcinoma (HPTC) with vascular invasion (VI), 32 papillary thyroid carcinoma (PTC) with VI and 225 PTC without VI. The mean follow‐up was 6.5 years with a range of 1‐17 years. The tumours were histologically subdivided into minimal or wide invasion for FC and HC and focal or extensive invasion for PTC and HPTC, and stratified according to status of VI. Results: The rate of distant metastasis was similar for FC, malignant Hürthle cell tumours and PTC with VI, and increased with extent of invasion. VI was seen in 12% of all PTC and 0% of HPTC in this study. PTC without VI were associated with a much lower potential of distant metastasis, were smaller in size and occurred in patients of younger age than PTC with VI. In addition, there was a tendency for increased potential for distant metastases with increased tumour size and patient age for all groups of tumours in the study. Patient age and tumour size appeared to play a smaller role than that of VI in predicting distant metastasis. Conclusions: Our study suggests that the rate of distant metastasis relates to VI, patient age and tumour size, regardless of Hürthle cell, FC or PTC differentiation. PTC of large size, and in patients older than 45 years, have a high propensity for vascular invasion.

Composite renal cell carcinoma and angiomyolipoma: a study of the histogenetic relationship of the two lesions.

The purpose of the present study was to investigate the possible histogenetic relationship of renal cell carcinoma (RCC) and angiomyolipoma (AMYL) occurring in the same renal nodule by examining two cases of composite RCC and AMYL in patients without stigmata of tuberous sclerosis and by reviewing the medical literature of similar cases. Case 1 represents an epithelioid variant of AMYL with multiple additional nodules of typical AMYL in a surgically removed kidney. The patient subsequently developed a lesion consisting of a mixture of epithelioid variant of AMYL and RCC 24 months later in the retroperitoneum and, an additional 4 months later, in the liver. The RCC cells resembled mononucleated epithelioid cells of the epithelioid AMYL except that they were focally reactive with epithelial membrane antigen (EMA) in the retroperitoneum and focally reactive with both EMA and cytokeratin (CK) in the liver. Case 2 consisted of a typical AMYL admixed with a chromophil cell RCC. A review of the medical literature revealed seven additional cases with histopathological findings similar to this case. All cases had multiple foci of typical AMYL. Immunostaining results are available in five tumors. Chromophil RCC showed variable reactivity with CK and EMA. In addition, RCC in the two cases in the present study also displayed a positive reaction with mucin staining and a positive reactivity with carcinoembryonic antigen. There appears to be a spectrum of histopathological and immunohistochemical changes from the epithelioid variant of AMYL through a mixed epithelioid AMYL/RCC to chromophil RCC in three successive specimens in case 1. Moreover, the intimate admixture of AMYL and RCC and the similar expression of epithelial markers of RCC in the two cases in the present study, as well as other cases in the literature, suggest that some RCC develop from the same precursor cell as AMYL or from a component of AMYL.

Immunohistochemical Study of Papillary Thyroid Carcinoma and Possible Papillary Thyroid Carcinoma-related Benign Thyroid Nodules

Recent immunohistochemical studies have identified different antisera that have various degrees of sensitivity and specificity for papillary thyroid carcinoma (PTC). In this study, we performed immunostaining for CK, EMA, HBME, CD57 and CD15 in PTC, and benign thyroid nodular lesions to compare the sensitivity and the specificity of these antisera for PTC. In addition, we studied the patterns of immunostaining of these antisera in benign nodular thyroid lesions displaying a fine chromatin pattern, foci of cells with nuclear grooves, and optically clear nuclei. Fifty-five PTC (composed of 30 papillary variants and 25 follicular variants), 5 follicular carcinomas, 30 follicular adenomas, and 20 thyroid nodular lesions (5 papillary variants and 15 follicular variants) were submitted for immunostaining with CK, EMA, HBME, CD57, and CD15. CK and HBME showed the highest sensitivity and specificity for PTC when an arbitrary cutoff of more than 10% positive cells was considered as positive diagnostic immunostaining for these sera. The other antisera were less sensitive and less specific. One case of PTC showed negative HBME but positive CD15, whereas three papillary variants and two follicular variants of benign thyroid nodules revealed a positive diagnostic HBME immunostaining for PTC and negative CK immunostaining. Any combination of positive diagnostic immunostaining with CK+ HBME, CK+ CD57 or CK+ CD15 has a sensitivity of 95% and specificity of 90% for PTC. Thyroid nodules with a diffuse or focal fine chromatin pattern and focal areas with nuclear grooves or optically clear nuclei displayed immunoreactivity ranging from 0% to 50% of cells. Three of five follicular carcinomas showed negative reactivity for HBME, CD57, and CD15. A combination of immunostaining with CK, HBME and CD57 (or CD15) is a sensitive and specific test for PTC. This panel can be used to rule out thyroid nodules posing a diagnostic problem with PTC. Follicular adenoma and nodules of the thyroid, with a fine chromatin pattern and focal nuclear grooves or optically clear nuclei, displayed an intermediate range of reactivity between reactive thyroid tissue and PTC.

Mammary Paget’s disease: Evidence of diverse origin of the disease with a subgroup of Paget’s disease developing from the superficial portion of lactiferous duct and a discontinuous pattern of tumor spread

The pattern of spread of intraductal carcinoma associated with mammary Paget’s disease has not been well studied. The purpose of this study was to examine the site of origin and the pattern of tumor spread with a three‐dimensional view by serial sectioning of the tissue blocks from 19 cases of Paget’s disease. Intraductal carcinoma in the superficial portion of the lactiferous ducts was seen in continuity with the overlying epidermis with Paget’s disease in all 19 cases. In seven cases that had adequate tissue sampling, five showed a continuous pattern of the intraductal carcinoma within the superficial as well as the deep breast tissue. In the remaining two cases, a portion of benign duct was identified between the intraductal carcinoma in the superficial lactiferous duct and the deep breast tissue. This discontinuous pattern of spread of the intraductal carcinoma was also identified in the foci of carcinoma in deep tissue. In the five cases in which the tumor involved the skin and only the superficial portions of the lactiferous duct, the leading edge of the intraductal carcinoma was seen orientated in the direction of the nipple towards the deep breast tissue. Our study of Paget’s disease demonstrated that in addition to tumor spread along the lactiferous ducts from intraductal carcinoma in the deep tissue towards the nipple, there was a group of Paget’s disease arising from the nipple. These lesions included: (i) lesions limited to the areolar tissue; and (ii) lesions with intraductal carcinoma involving the duct system in both superficial and deep breast tissue with and, possibly, without skip areas pattern of spread. Although certain cases of Paget’s disease may appear superficial, an independent associated carcinoma in deep breast tissue has to be ruled out.

Development of endometriosis from embryonic duct remnants

Among 18 cases of endometriosis involving ovaries and fallopian tubes, we identified three cases with foci of endometriosis adjacent to the embryonic duct remnants in the fallopian tube. The serial sections of the blocks of tissue containing areas of interest showed segments of embryonic duct remnants with changes suggestive of gradual transformation to endometrial glands. The early changes consisted of replacement of the muscular coat surrounding the epithelium of embryonic duct remnants by the endometrial stroma with positive immunoreactivities for estrogen receptor. Subsequently there were changes of the embryonic duct remnant epithelium into endometrial epithelium with diffuse immunoreactivities for estrogen receptor. The significance of this transformation as a mechanism of development of endometriosis is discussed.