José I. López

Renal angiomyolipoma: clinicopathologic study of 194 cases with emphasis on the epithelioid histology and tuberous sclerosis association.

The majority of renal angiomyolipoma (AML) is sporadic and occasionally it occurs as part of tuberous sclerosis complex (TSC). Epithelioid AML (EAML), an uncommon variant, is considered potentially malignant based on anecdotal case reports. The prognostic significance of epithelioid component in an otherwise typical AML is uncertain. We studied 194 AMLs for the clinicopathologic features of epithelioid and TSC-associated AMLs. Epithelioid component was present in 15 cases (7.7%) with an average amount of 51% (range: 10% to 100%). Histologically, the epithelioid tumor cells were categorized into small, intermediate, and large cell type based on the cell size. Worrisome histologic features were seen in many EAMLs, including coagulative tumor necrosis in 27% (4/15), nuclear atypia in 93% (14/15), mitosis in 47% (7/15), and atypical mitosis in 1 case. All 15 EAML patients had a mean follow-up time of 5.1 years and none had local recurrence or distant metastasis. Sixteen (8.2%) AMLs occurred in patients with definitive TSC. Three histologic features, namely microscopic AML foci, epithelioid component, and epithelial cysts, were present in 10 (62.5%), 4 (25%), and 44% (7/16), respectively, of TSC-associated AMLs, compared with 11 (6.2%), 11 (6.2%), and 6 (3.4%), respectively, in non–TSC-associated AMLs (P value all <0.01). In summary, all 15 cases of EAMLs in our study had benign clinical outcomes despite adverse pathologic features. Epithelioid component, epithelial cysts, and microscopic AML foci are strongly associated with TSC and the presence of all 3 features should raise strong suspicion for TSC.

Tubulocystic Carcinoma of the Kidney Clinicopathologic and Molecular Characterization

The nature of tubulocystic carcinoma, a rare renal tumor composed of tubular and cystic structures, is poorly understood. It has been suggested that it may represent a low-grade collecting duct carcinoma of the kidney despite the lack of sufficient molecular and pathologic evidence. The aim of this study was to examine the clinical and pathologic features of 13 cases of tubulocystic carcinoma of the kidney. Furthermore, using gene expression microarray analysis, we defined the molecular signature of this tumor by comparing it with other renal tumors in our previously established molecular profile database. Histologically, all 13 tumors were composed of closely packed tubules and cysts of varying sizes separated by fibrovascular septa. The epithelial lining cells of the tubules and cysts in this tumor were characterized by abundant eosinophilic cytoplasm with prominent nucleoli often showing a hobnail appearance. Clinically, one of the 13 cases showed metastasis to the pelvic lymph nodes. Five of the 13 cases coexisted with papillary renal cell carcinoma (RCC) (n=3) or papillary adenoma (n=2). In addition, the molecular profile of tubulocystic carcinoma was similar but not identical to those of papillary RCC by clustering analysis. Through comparative genomic microarray analysis, tubulocystic carcinoma showed gains of chromosome 17, but not chromosome 7, whereas most papillary RCCs showed chromosomal gains in both 7 and 17 (trisomies). Therefore, based on its unique pathologic features and molecular signature as well as its biologic behavior to develop metastasis either by itself or in association with papillary RCC, tubulocystic carcinoma of the kidney should be recognized as a distinct subtype of RCC and be distinguished from other malignant and benign cystic lesions of the kidney.

Renal tubulocystic carcinoma is closely related to papillary renal cell carcinoma: implications for pathologic classification.

Tubulocystic carcinoma of the kidney (TC-RCC) is a rare renal tumor with unique gross and microscopic features unlike other types of renal cell carcinoma (RCC). Several recent studies recommend that it should be classified as a distinct RCC subtype. In this study, we provide pathologic and cytogenetic evidence supporting that TC-RCC is closely related to papillary RCC (PRCC). This study included 20 cases of renal tumors that partially or exclusively comprised a TC-RCC component. Pathologic examination documented the gross and microscopic features of TC-RCC, including multicentricity and the presence of concomitant PRCC and papillary adenoma. Formalin-fixed, paraffin-embedded sections from 12 TC-RCC and 20 PRCC were subjected to a multicolor fluorescence in situ hybridization assay containing probes for chromosomes 7, 17, and Y. One hundred nuclei were examined to enumerate the copy numbers of chromosomes in each tumor and its corresponding normal kidney tissue. A tumor with a percentage of cells harboring a chromosomal change ≥mean+3 SD of normal tissue was considered to harbor that chromosomal change, and a tumor with a percentage of cells with null Y chromosome count (loss of Y chromosome) ≥mean+3 SD of normal tissue was considered to harbor Y chromosome loss. Four of the 20 TC-RCCs were multicentric. Ten had associated PRCC or papillary adenoma within the same kidney as the TC-RCC. In 4 cases, the tubulocystic and papillary components were admixed together within the same lesion. The tumor cells lining both the tubulocystic and papillary components had similar cytologic features. Ten of 12 TC-RCCs had a chromosome 7 gain, 8 of 12 cases had a chromosome 17 gain, and 8 of 9 cases had a loss of Y chromosome. Six of 9 cases with all 3 chromosomes studied had a gain of chromosomes 7 and 17 and a loss of Y chromosome. Our study shows that TC-RCCs and PRCCs are closely related entities. With its distinctive gross and microscopic features, TC-RCC may be considered a unique “morphologic entity.” However, before it is accepted as a distinct renal cell carcinoma subtype, further studies are needed to document a characteristic molecular signature associated with this tumor.

The prognostic significance of vascular invasion in stage T1 bladder cancer

Transurethral resection specimens from 170 T1 bladder carcinomas were reviewed for the presence of vascular (blood vessel and/or lymphatic) invasion by tumour cells. Such a finding was noted in 17 cases (10%), and occurred most frequently in high grade tumours. Tumour recurrence was documented in 11 of these cases (65%), including seven patients who showed progression to more invasive disease (T2–T4) and six patients (55%) who died of disease. Five‐year survival for cases without vascular invasion was 81% versus 44% for those with. This was a statistically significant difference (log‐rank, P= 0.004). Neoplasms of high grade (grades 2 to 3), without a papillary configuration, and exceeding 5 cm were associated with vascular invasion (chi‐squared: P < 0.001, P= 0.043, and P= 0.061 respectively). In multivariate analysis vascular invasion proved to be an independent prognostic factor (Coxs regression, P= 0.015). We therefore stress the clinical relevance of a thorough evaluation of the state of vascular invasion in stage T1 bladder cancer.

Basaloid-squamous cell carcinoma of the larynx and hypopharynx. A clinicopathologic study of 7 cases.

During a 16-year period (1974-1989), a retrospective review of 468 surgical specimens of laryngectomy yielded 7 cases (0.66%) of basaloid-squamous cell carcinoma. They were all males between 42 and 63 years of age. Four cases were supraglottic and one transglottic. The other two arose in the left pyriform sinus and vallecula, respectively. At diagnostic time, 4 cases were Stage III and 2 Stage IV, only one being Stage II. Glanz index of histologic malignancy was high (> 5) in most cases (6/7). Mitotic rate was also high (22-78 mitoses/10 HPF). Lymph node metastases were documented at diagnosis in 5 cases, 3 of them presenting with extracapsular extension. One case developed liver metastases. During the follow-up, lymph nodes of the neck were again metastasized in 4 cases, and stomal recurrence was present in another one. Death of disease was confirmed in 5 cases after 10 to 35 months of follow-up. Overall survival was 28.5% after 3 years.

Primary Cisplatin, Methotrexate and Vinblastine Aiming at Bladder Preservation in Invasive Bladder Cancer: Multivariate Analysis on Prognostic Factors

PURPOSE Although radical cystectomy is the standard therapy for invasive bladder cancer, cisplatin based multi-drug chemotherapy has proved to be effective for advanced transitional cell urothelial carcinoma. The potential for bladder preservation with neoadjuvant chemotherapy is currently under investigation. MATERIALS AND METHODS A phase 2 protocol is presented for conservative treatment of muscle invasive transitional cell carcinoma of the bladder consisting of primary cisplatin, methotrexate and vinblastine chemotherapy followed by reevaluation for bladder sparing surgery and surveillance. A total of 61 patients completed the protocol with a mean followup of 41.4 months. RESULTS Initial complete response to chemotherapy associated with tumor stage, size and configuration was noted in 20 patients (33%). Bladder preservation, intended only for the complete response group, was achieved in 16 patients (26%) but only 11 (18%) were alive with the bladder intact at study closure. Disease-free 5-year survival rate was 47% (95% confidence interval 65 to 26%). Tumor stage (p = 0.0007), size (p = 0.0003), response to chemotherapy (p = 0.002), patient age (p = 0.039) and tumor grade (p = 0.048) influenced survival. Multivariate analysis revealed response to chemotherapy (beta = 0.988, p = 0.034) and tumor size (beta = 0.978, p = 0.042) to be the only independent predictors. CONCLUSIONS Induction of cisplatin, methotrexate and vinblastine chemotherapy is helpful in identifying patients with a greater chance for survival among those with locally advanced bladder cancer. However, a bladder preservation strategy based on this therapy is only of limited success.

Pseudosarcomatous Myofibroblastic Proliferation of the Bladder: Report of 2 Cases and Literature Review

We report 2 cases of pseudosarcomatous myofibroblastic proliferations of the bladder unrelated to urological trauma. To our knowledge, these cases represent the longest followup (12 and 19 years, respectively) reported in the literature, which confirms the long-term benign nature of an entity that may be clinically and even pathologically mistaken as malignancy. A review of the literature revealed a female predominance (3:1), 50% of the cases manifested in the first 2 decades of life and mean age was significantly lower in male patients (p < 0.005). These facts suggest the existence of a hormonal factor in the pathogenesis of this entity. A predilection for fundus, and the posterior and lateral walls also is demonstrated. In light of the complex embryogenesis of the cloacal territory, it could be hypothesized that this lesion arises from embryonal mesenchymal remnants of the endodermally derived urinary tract.

Burned-out Tumour of the Testis Presenting as Retroperitoneal Choriocarcinoma

A case of “burned-out” tumour of the testis in a 20-year-old man is reported. The tumour presented as widespread retroperitoneal metastases. Orchiectomy displayed a subalbugineal fibrous scar close to the rete testis. Diagnostic biopsy of the unresectable retroperitoneal tumour showed a choriocarcinoma. Although appropriate chemotherapy was promptly started, the patient died 7 months after the initial complaints.

Significance of granulomas in bone marrow: A study of 40 cases

Granulomas in bone marrow are an infrequent finding related to diverse disease. We reviewed 8057 bone marrow studies made over a period of 10.5 years, confirming the presence of granulomas in 40 patients. Global incidence was 0.50% and annual incidence 3.80 cases/yr. Because of the non‐specificity of the morphological data, the diagnostic significance of the finding is limited, but it does serve to narrow the field of etiological possibilities. Associated disease was demonstrated in 82.5%, infectious diseases being the most common (tuberculosis, brucellosis, typhoid fever and kalaazar). Two previously unpublished entities are introduced: refractory anemia with excess blast cells (dysmyelopoietic syndrome) and malignant histiocytosis. 3 patients presented human immunodeficiency virus infection, the etiopathogenic role of this retrovirus in the generation of granulomas being unknown. The efficacy of bone marrow study in demonstrating granulomas increases if both the aspirate clot and bone cylinder are examined.

Histopathology of Diaphragm Disease of the Small Intestine A Study of 10 Cases From a Single Institution

Diaphragm disease (DD) is an uncommon gastrointestinal abnormality typical of nonsteroidal anti-inflammatory drug (NSAID)-induced injury. DD of the small intestine is well defined in its gross appearance (multiple circumferential stenosing lesions); however, its histologic features have been studied in few cases. To better define and update the histologic features of DD, we describe 10 cases in which patients underwent resection of portions of small intestine for DD. Selected gross features and 12 microscopic features were assessed. The typical gross appearance of DD was associated with focal chronic injury of the mucosa with mild to moderate inflammatory infiltrate. A wide array of additional abnormalities was found: eosinophilic enteritis (3 cases), inflammatory fibroid polyp (1 case), enteritis cystica profunda (1 case), villous atrophy (1 case), and neuromuscular and vascular hamartoma-like changes (9 cases). DD and, therefore, NSAID-related injury, should be considered in the differential diagnosis of several conditions affecting the small intestine.