Walid A. Mourad

Fine-needle aspiration biopsy diagnosis of small round cell tumors of childhood: A comprehensive approach

Fine‐needle aspiration biopsy findings in small round cell malignant tumors of children are briefly reviewed. All of these tumors usually have characteristic cytomorphology which, when recognized, may lead to a definitive diagnosis. However, when these tumors are undifferentiated, morphologic criteria may not be sufficient for arriving at a correct diagnosis. A variety of ancillary studies including electron microscopy, immunohistochemistry and DNA ploidy, cytogenetics, and fluorescent in situ hybridization may provide valuable additional information for precise characterization of these neoplasms. Some of the ancillary studies may also be used for assigning these cases to prognostically significant subgroups. This information may also help in defining the most suitable chemotherapeutic regimens for these tumors. Since most of these special studies require only a small amount of cellular material, fine‐needle aspiration biopsy is ideally suited for obtaining samples for these procedures. It is hoped that as cytogenetic and molecular techniques become available in many diagnostic laboratories, a comprehensive evaluation of aspiration biopsies from round cell malignant tumors, encompassing a precise pathologic diagnosis, determination of prognosis, and prediction of response to therapy, will be possible in a majority of cases. Diagn. Cytopathol. 1999;21:81–91.

Stevens-Johnson syndrome in patients on phenytoin and cranial radiotherapy.

The use of phenytoin as a prophylactic anticonvulsant after brain surgery, particularly for brain tumors, is a common practice, regardless of whether the patient has a previous history of convulsions. This treatment policy assumes that the benefits exceed the risks. Four cases are described of adverse reactions to phenytoin during the concomitant use of cranial radiotherapy. In one patient this proved fatal. There is increasing anecdotal support in the literature for a synergistic effect between phenytoin therapy and cranial radiotherapy that can result in the life-threatening Stevens-Johnson syndrome. While the association is uncommon, four cases within 24 months in one department suggest that the routine use of postoperative phenytoin as a prophylactic anticonvulsant in the absence of a history of seizures may not be warranted, particularly if the patient is to receive cranial radiotherapy.

T-cell/histiocyte-rich B-cell lymphoma: Clinical presentation, management and prognostic factors: report on 61 patients and review of literature

T-cell/histiocyte-rich B-cell lymphoma (TC/HRBCL) is a rare subtype of diffuse large B-cell non-Hodgkins lymphoma (DLBCL) with characteristic morphologic and immunophenotypic features, often misdiagnosed as Hodgkins lymphoma and peripheral T-cell lymphoma. Few and conflicting clinical data are available in the literature addressing optimal treatment, prognosis and outcome. We retrospectively reviewed all patients diagnosed and managed at our institution between 1995 and 2004 diagnosed with T-cell-rich-B-cell lymphoma by WHO criteria. Sixty-one patients were identified. Initial pathology was incorrect in 82% of referred cases. The median age was 30 years. Seventy-one patients were males. Stage distribution was I – II in 21 patients, and III – IV in 40. Fifty-two percent of patients (32) had splenic involvement and thirty-seven patients (61%) presented with extranodal disease (22 ≥ 2 sites). The International Prognostic Index (IPI) score was ≥2 in 62% of patients. All 59 newly diagnosed TC/HRBCL patients were treated with CHOP or R-CHOP combination chemotherapy +/− radiation therapy. The overall response rate was 85% and nine patients progressed on therapy. Fourteen patients relapsed with a median time of relapse of 6 months (range, 2 – 28). At a median follow-up of 22 months (range 1 – 132); 32 patients (52%) are alive with no evidence of disease. The 5-year overall survival and event free survival rates were 46% and 39% respectively. To conclude, TC/HRBCL is difficult to recognize without immunohistochemistry. It has an aggressive course and poor outcome; with most of patients presenting with advanced disease stage together with high IPI score. Treatment outcome seems to be similar to IPI matched DLBCL counterpart.

The correlation of two argyrophilic nucleolar organizer region counting methods with bromodeoxyuridine-labeling index: A study of metastatic tumors of the brain

Bromodeoxyuridine (BrdU) is a thymidine analog that is incorporated into cellular DNA in the synthetic phase. The BrdU-labeling index (BLI) thus reflects the S-phase fraction. The argyrophilic nucleolar organizer regions (AgNORs) are silver-stained granules that have been correlated with ploidy and/or S-phase fraction. Two AgNOR counting methods have been proposed to distinguish between ploidy and S-phase fraction: the mean AgNOR (mAgNOR) count (the mean number of AgNOR granules in 100 cells), which is believed to reflect ploidy, and the AgNOR proliferative index (pAgNOR) (the percentage of cells exhibiting five or more AgNOR granules per nucleus), which is believed to reflect S-phase fraction. To evaluate the latter hypothesis we studied 19 tumors metastatic to the brain in patients who had received preoperative low-dose BrdU injections. Formalin-fixed, paraffin-embedded sections of the resected tumors were stained using the indirect immunoperoxidase technique and a monoclonal antibody to BrdU. The BLI was determined by counting 1,000 tumor cells in each case; AgNOR silver staining was performed on sections of the same blocks studied for BLI. The correlation between pAgNOR counts and BLI was statistically significant (r = .649, P = .003). No statistically significant correlation could be obtained between mAgNOR counts and BLI (r = .421, P = .17). We conclude that the pAgNOR count can reliably reflect the proliferative activity of cells. The method can prove beneficial in situations in which cell kinetic analysis is needed and in which invasive procedures, such as BrdU injection, are not feasible or are contraindicated.

Cytomorphologic features of fine-needle aspiration of liposarcoma

The cytomorphologic features of fine‐needle aspirates (FNA) of liposarcomas have not been fully characterized. In the current study, we attempted to identify cytological attributes of liposarcoma in FNA. Twelve FNAs of histologically proven liposarcomas were used for this study. They included 10 myxoid and two well‐differentiated liposarcomas. Four cytological criteria were chosen for evaluation. These included a complex capillary network, increased cellularity, the presence of a metachromatic stroma for myxoid liposarcoma, and finally the identification of lipoblasts. Eighteen FNAs of lipomas and 17 FNAs of nonlipomatous soft‐tissue sarcomas were used as controls for evaluation of the same features. The diagnosis of liposarcoma had been rendered on FNA in 7 cases (58%). The diagnosis was suggested in 3 cases (25%), and a suggestion of sarcoma was rendered in 2 cases. Complex capillary networks were identified in 9 of 12 cases (75%); this was seen in 8 of the 10 myxoid liposarcomas and 1 of the 2 well‐differentiated neoplasms. Increased cellularity was seen in 7 of 12 cases (58%), metachromatic stroma was seen in 3 of 12 cases (25%), and lipoblasts were identified in 4 of 12 cases (33%). None of the lipomas or sarcomas exhibited a complex capillary network. When capillaries were identified in lipomas, they were straight, with minimal branching. The lipomas did not show evidence of increased cellularity in any cases. Metachromatic stroma was more frequently seen in the nonlipomatous sarcomas than in the liposarcomas. No lipoblasts were identified in any of the control FNAs. Diagn. Cytopathol. 1999;20:67–69.

Successful grading of renal-cell carcinoma in fine-needle aspirates†

Early‐stage renal‐cell carcinoma is more frequently diagnosed due to more frequent use of advanced radiologic techniques. Partial nephrectomy may be curative for small tumors and may sometimes be necessary if the opposite kidney is functionally compromised. This therapeutic option is however not possible in high‐grade neoplasms. In the current study, we attempted to grade cases of renal‐cell carcinoma on smears obtained from preoperative fine‐needle aspirates (FNA). Eighteen cases of histologically proven renal‐cell carcinoma formed the basis of this study. FNAs were performed prior to nephrectomy. FNA smears were blindly reviewed, and the cases were evaluated for cellularity, nuclear to cytoplasmic (N/C) ratios, nuclear pleomorphism, and the presence of naked nuclei and prominent nucleoli; cases were graded according to the presence or absence of these criteria and their combination. The cases were cytologically graded from grade I–IV and then were given a low grade if the tumor was considered grade I or II, or high grade if the tumor was considered grade III or IV. The histology of the neoplasms was reviewed, and the tumors were graded according to the Fuhrman nuclear grading system. Correlation between the cytologic and histologic grades within the same histologic grade was seen in 13 of the 18 cases (72.2%). The difference was no more than one grade for each discrepancy. When grading as high or low grade was used, agreement was seen in 100% of the cases. The most reliable cytologic features seen on cytology distinguishing low‐ from high‐grade tumors were the N/C ratio and the presence or absence of nucleoli. Pleomorphism, naked nuclei, and increased cellularity were less distinguishing features. We conclude that grading of renal‐cell carcinoma can be reliably achieved in FNA material. Preoperative FNAs can thus be performed on small renal neoplasms with subsequent conservative treatment if the tumor proves to be low grade. Diagn. Cytopathol. 2000;22:223–226.

Clear cell melanoma of the bladder

Primary malignant melanoma of the urinary bladder is a rare tumor. A case in a 34-year-old man who presented with gross hematuria is reported. Cystoscopic biopsy showed a mixed spindle cell and clear cell neoplasm with focal pigmentation. The tumor cells were immunoreactive for S-100 protein and HMB-45. The patient did not have a history of melanoma, and clinical and radiologic work-up did not reveal other lesions, so a partial cystectomy and pelvic lymphadenectomy were performed. The tumor formed an ulcerated mass that extended into the perivesicular fat. Microscopically, the tumor was composed predominantly of clear cells in sheets or small nests. A solitary metastatic focus was present in 1 of 25 pelvic lymph nodes. Ultrastructurally, the tumor cells were characterized by irregular nuclear contours, complex nucleoli, abundant cytoplasmic glycogen, and premelanosomes.

Cytomorphologic Differentiation of Hodgkin’s Lymphoma and Ki-1+ Anaplastic Large Cell Lymphoma in Fine Needle Aspirates

OBJECTIVE To cytomorphologically differentiate Hodgkins lymphoma (HL) from Ki-1+ anaplastic large cell lymphoma (ALCL) in fine needle aspirates. STUDY DESIGN We blindly reviewed 63 fine needle aspiration (FNA) smears from histologically and immunophenotypically proven cases of ALCL (n = 15) and HL (n = 48). The smears were reviewed for the following criteria: (1) estimated percentages of abnormal cells, (2) pattern of the smears (polymorphous vs. dimorphous), and (3) presence or absence of multilobated cells. RESULTS All cases were phenotyped by immunohistochemistry for CD3, CD15, CD20, CD30 and CD45, with flow cytometric immunophenotpyping in 41 cases. Flow cytometric phenotyping was not successful in any of the cases. The smears were polymorphous in all 15 cases of ALCL and in 1 case of HL (2%). The percentage of abnormal cells ranged from 10% to 90% in cases of ALCL (median, 30%) whereas it ranged from 1% to 25% in HL (median 3%; P = .0003). Three cases of HL showed abnormal cells constituting > or = 20% of the smears. They were all grade 2 disease. Multilobated cells were identified in 14 of the 15 cases of ALCL (93%) and in 3 of the 48 cases of HL (6.25%; P = .0008). CONCLUSION Our findings indicate that the differentiation of ALCL from HL can be achieved in FNA smears through identification of abnormal cells representing > 30% of the population, a spectrum of abnormal cells and the presence of multilobated nuclei. Rare cases of grade 2 HL may be difficult to differentiate from ALCL.

Fine-needle aspiration cytology of sarcomatoid carcinoma of the breast: A cytologically overlooked neoplasm

Sarcomatoid carcinoma of the breast is a very uncommon neoplasm. Fine‐needle aspiration findings have been rarely reported. We report a case of sarcomatoid carcinoma of the breast that was diagnosed as a typical ductal carcinoma cytologically. The patient was a 45‐year‐old female who had a right breast mass for a short duration. Fine‐needle aspiration (FNA) showed smears predominantly composed of single cells exhibiting plasmacytoid features with moderate degree of pleomorphism. A granular bluish background was noted on the Papanicolaou‐stained smears. This background was thought to represent tumor diathesis, and the diagnosis of grade II ductal carcinoma of the breast was rendered. The patient underwent a subsequent lumpectomy with axillary node dissection. Histological examination of the lumpectomy revealed a neoplasm predominantly composed of a grade II chondrosarcoma with increased cellularity. A small (10%) component showed grade II invasive ductal carcinoma of the breast. No in situ component was seen. The sarcomatoid component was positive for S‐100 protein and vimentin and negative for keratin, whereas the carcinomatous component was positive for vimentin, epithelial membrane antigen, and low molecular weight keratin. Ultrastructurally, the tumor showed features of a poorly differentiated epithelial neoplasm without evidence of chondrosarcoma. Metastases were seen in seven of ten axillary lymph nodes with exclusive epithelial component. Retrospective evaluation of the FNA smears revealed an extensive metachromatic stroma on the DIFF QUIK™‐stained smears. Our findings and review of the literature suggest that sarcomatoid carcinoma of the breast will be very frequently overlooked or misdiagnosed either because of the subtlety of the stroma or the predominance of the mesenchymal component. Our findings also provide supportive evidence that the use of the DIFF QUIK™ stain can be very helpful in the identification of the stroma in this neoplasm. The predominance of epithelium in the metastases in our case is further proof that tumors with dual differentiation such as sarcomatoid carcinomas and mixed muellerian tumors are truly carcinomas with metaplastic features. Diagn. Cytopathol. 16:242–246, 1997.

Liposarcoma: A clinicopathological study of 73 cases diagnosed at King Faisal Specialist Hospital and Research Centre.

BACKGROUND Liposarcoma is one of the most common adult soft tissue sarcomas, being second only to malignant fibrous histiocytoma. It ranges from the well-differentiated lipoma-like and myxoid tumors, to extremely cellular or pleomorphic malignant neoplasms. The clinical behavior is variable and reflects the variable microscopic picture. PATIENTS AND METHODS Clinicopathological studies of liposarcoma in Saudi Arabia are lacking. In this study, we reviewed all liposarcoma cases reported at KFSH&RC from 1981 to 1996. Seventy-three cases of liposarcoma were studied morphologically. The cases were classified using the WHO International Classification of Diseases (ICD). Data regarding follow-up, mode of therapy, recurrence and survival status were available for 37 cases (50.68%). Survival analysis was performed. The patientsâ ages ranged from 15-94 years, with peak incidence between the ages 40 and 60 years. There was a male predominance of 1.3:1. RESULTS The most common location was the thigh (36 cases), accounting for 49.3% of cases, followed by the retroperitoneum (16 cases), accounting for 21.9%. The most common histologic type was myxoid liposarcoma (41 cases; 56.2%), followed by well-differentiated liposarcoma (16 cases; 21.9%), including dedifferentiated liposarcoma (5 cases; 6.8%), pleomorphic liposarcoma (13 cases; 17.8%) and round-cell liposarcoma (3 cases; 4.1%). Twenty-two patients (59.45%) were treated by surgery only, and 13 patients (35.13%) were treated by a combination of surgery and postoperative radiotherapy. One patient was treated by surgery, radiotherapy and chemotherapy, and died one month after diagnosis. Another patient was treated by radiotherapy alone and is still alive after a four-year follow-up period. The correlation between survival and recurrence with tumor type, location in regard to surgical accessibility, and mode of therapy, was not statistically significant. CONCLUSION Site, histologic type and completeness of surgical excision were the most important factors in predicting prognosis and planning therapy for patients with liposarcoma. The overall prognosis depends on many variable factors. Complete surgical excision reduces the recurrence rate. The role of chemotherapy and radiotherapy is not well established.