Diagnosis of anaplastic large-cell lymphoma, including multifocal osseous KI-1 lymphoma, by fine-needle aspiration biopsy.

We present the fine-needle aspiration (FNA) findings of 4 cases of anaplastic (Ki-1) large-cell lymphoma (ALCL). A primary diagnosis of ALCL was made on FNA material in 2 cases, of which one was a multifocal osseous Ki-1 lymphoma. In the other 2 patients who had a known history of ALCL, FNA was used to detect recurrent disease. In all cases, large discohesive pleomorphic cells in the absence of lymphoglandular bodies in the background raised the possibility of a nonhematopoietic neoplasm. Immunochemical staining for CD30 was positive in all cases. The cytomorphologic and immunochemical features are discussed, along with the differential diagnosis of Ki-1 lymphoma. Diagn. Cytopathol. 1999;21:174-179.

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

Marginal zone B cell lymphomas (MZBCLs) represent a category of non-Hodgkin's 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.

Hodgkin's disease with lymphocyte predominance: long-term results based on current histopathologic criteria.

PURPOSE: To define the disease course, therapeutic strategies, patterns and rates of relapse and causes of death for patients with Hodgkin's disease with lymphocyte predominance (LPHD) and to assess prognostic factors including nodular and diffuse histologic patterns. PATIENTS AND METHODS: The records of all previously untreated patients with LPHD who received initial treatment at the University of Texas M. D. Anderson Cancer Center (UTMDACC) from 1960 through 1992 were reviewed. Clinical and histopathologic characteristics, specifically nodular and diffuse LPHD, and treatment groups were assessed by overall and relapse-free survival, patterns of relapse, and causes of death. RESULTS: Of 70 patients, 58 (83%) had nodular LPHD and 12 (17%) had a diffuse pattern: clinical characteristics were similar between the two subtypes. The median age of all patients was 25 years, 79% were male, 96% presented with stage I or II disease and 93% were free of B symptoms. Laparotomy (23 patients) failed to upstage any patient with a negative lymphogram. With a median follow-up of 12.3 years for alive patients, 19 (27%) patients have relapsed. All 3 relapses among the patients with diffuse subtype occurred within 3 years while 9 of 16 relapses occurred after 5 years with nodular subtype. However, we did not detect any statistically significant difference in relapse free survival or survival between the subtypes in our patient population. There was some suggestion that patients aged 40 and older experienced shorter survival; no other pretreatment characteristics were noted to be associated with relapse free survival or survival. Though there were no relapses within the radiation fields, no effect of extent of radiation therapy on relapse rate was observed. Thirteen (19%) patients have died, 6 (8.6%) of whom succumbed to LPHD. Two patients developed diffuse large cell lymphoma. CONCLUSIONS: Patients with LPHD usually present with localized and asymptomatic disease. Laparotomy is unnecessary if the lymphogram is negative. Nodular histology occurred in the majority of patients. Though all relapses from diffuse subtype occurred within 3 years in contrast to some late relapses observed for nodular subtype, there was no statistically significant difference in relapse free survival or survival between the subtypes. The extent of irradiation had no effect on relapse free survival or survival. We could not find any evidence that LPHD should be treated any different from the classical Hodgkin's disease at this point despite suggestions that it be classified as a non-Hodgkin's B-cell lymphoma.

Plasma cell granuloma of the oral cavity: a report of two cases and review of the literature.

We report two rare cases of plasma cell granuloma arising in the extragingival oral cavity. These are tumorous proliferations composed predominantly of reactive plasma cells. Both patients presented with solitary mass lesions that were clinically suspicious for malignancy. One patient presented with a mass that grew slowly for 2 years and involved the lip; in the second patient, a mass developed in the buccal mucosa Histologically, both lesions were characterized by lobules of plasma cells separated by thick collagenous bands. A variable number of admixed lymphocytes and histiocytes was noted in both cases. In situ hybridization and immunostaining for kappa and lambda light chains revealed a polyclonal plasma cell population. In situ hybridization for Epstein-Barr virus failed to demonstrate evidence of viral expression in either case. Both patients are free of disease after 8-month and 12-month follow-ups. Although plasma cell granuloma in the oral cavity is rare, it is important to recognize this entity as a benign inflammatory lesion.

CD5+ low-grade marginal zone B-cell lymphomas with localized presentation.

Marginal zone B-cell lymphomas (MZBCLs) are low-grade lymphomas that characteristically lack CD5 expression. However, rare cases of MZBCL have been described in which the lymphomatous B cells coexpress CD5 (CD5+ MZBCL). In 7 of 9 reported CD5+ MZBCLs, there was evidence of widespread disease. We report four additional cases of CD5+ MZBCL. Three cases were low-grade B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) involving the lungs, the conjunctiva (bilateral), and the uterus. The remaining case represented a monocytoid B-cell lymphoma involving a posterior cervical lymph node. Southern blot hybridization did not show rearrangements of bc11 or bc12 in the three cases analyzed. All four patients had localized disease and normal peripheral blood counts. Staging of bone marrow biopsies from three patients did not show evidence of bone marrow involvement. The remaining patient had bilateral conjunctival lesions that were present for 15 years without progression. These four additional cases of CD5+ MZBCL show that this group of low-grade B-cell lymphomas occasionally may exhibit an atypical phenotype. Furthermore, in this study, the CD5+ MZBCLs were clinically localized at presentation, in contrast to most other reported cases, which have had dissemination to bone marrow or peripheral blood.

The pattern of p53 and p21WAF1/CIP1 immunoreactivity in non-Hodgkin's lymphomas predicts p53 gene status.

P53 and p21WAF1/CIP1 (p21) immunostaining was performed on 92 non-Hodgkin's lymphomas (NHLs), and the staining pattern correlated with the presence or absence of p53 hot spot mutations as detected by PCR-SSCP of exons 5-8 and direct sequencing. Twenty-nine of 92 lymphomas overexpressed p53, and 17 overexpressed p21. Of the p53 overexpressing lymphomas, 14 also overexpressed p21, and none of these 14 harbored a detectable hot spot mutation. However, mutations were detected in 13 (87%) of 15 p53 overexpressing, p21 negative lymphomas. One of the 63 p53-negative lymphomas harbored a detectable hot spot mutation, and it was also negative for p21. These results demonstrate that among NHLs that overexpress p53 protein, those which also show p21 overexpression do not harbor p53 hot spot mutations, and furthermore, provide evidence that the transactivating function of p53 is retained. On the other hand, p53 overexpression in NHLs that lack p21 expression is usually indicative of p53 gene mutation.

Malignant granular cell tumor: a case report and review of the recent literature.

We report a case of an extremely rare neoplasm, malignant granular cell tumor (MGCT). The tumor occurred in the infratemporal fossa of a 30-year-old man, extended to the left orbital base, into the foramen ovale, and invaded the mandible. A granular cell tumor (GCT) was diagnosed by fine-needle aspiration and core needle biopsy of the mass. The patient underwent a radical subtotal debulking procedure followed by radiotherapy. He is alive with recurrent disease 12 months after presentation. Cytologically, the aspirated material was abundantly cellular showing large polygonal cells with ample granular eosinophilic cytoplasm, eccentric nuclei, and often prominent nucleoli. Histologically, the tumor consisted of solid sheets of similar cells that stained strongly with S-100 protein, neuron-specific enolase (NSE), and vimentin. There was moderate nuclear pleomorphism and broad zones of necrosis. Four mitotic figures per 100 high-power field (HPF) were counted. By electron microscopy, the cytoplasm of the tumor cells was filled with lysosomes. Although, some observers advocate that the diagnosis of a MGCT should be reserved for cases in which lymph node and/or distant organ metastasis is evident, we believe malignancy ought to be considered in any GCT with aggressive clinical course defined by persistent local recurrence and destruction of neighboring structures. Nuclear pleomorphism, necrosis, and presence of any mitotic activity should indicate malignancy.

Follicular lymphoma adjacent to foreign body granulomatous inflammation and fibrosis surrounding silicone breast prosthesis.

Silicone lymphadenopathy has been associated with fracture and/or erosive breakdown of silastic implants in joint replacements and is also known to occur with cosmetic and reconstructive breast implant surgery. In the orthopedic literature rare malignant lymphomas have been reported in association with silicone granulomas in lymph nodes; whether silicone is a causative agent remains controversial. We report a single case of a 56-year-old woman who had painful capsular contractures and a 2-cm palpable nodule medial to her silicone mammary implant. Histologically the mass comprised an extra nodal follicular mixed lymphoma with surrounding granulomatous response to polarizable foreign body material. Paraffin immunophenotyping, bcl-2 protein staining, and gene rearrangement analysis verified this diagnosis.

Nasopharyngeal lymphoid tissue masses in patients with human immunodeficiency virus-1. Histologic findings and clinical correlation.

BACKGROUND: Although the histologic changes in lymph nodes in patients infected with the human immunodeficiency virus-1 (HIV-1) are well described, the histology and resulting clinical symptoms of hyperplastic nasopharyngeal lymphoid tissue (NPLT) in these patients are not widely known, particularly to pathologists and oncologists. METHODS: Nine patients with HIV-1 presented with a nasopharyngeal mass, nasal stuffiness, nasal bleeding, hearing loss, and cervical lymphadenopathy in various combinations. Tonsillar tissue was biopsied or removed from all nine. RESULTS: The tonsillar tissue showed a spectrum of the changes of reactive lymphoid hyperplasia. CONCLUSIONS: Clinicians and pathologists must be aware of the spectrum of histologic changes and clinical features relating to biopsies from NPLT to interpret the changes correctly and to avoid a misdiagnosis of malignant lymphoma.

True histiocytic lymphoma with multiple skin nodules.

A 73-year-old white woman developed multiple cutaneous nodules that fluctuated in size and occasionally regressed. The tumor cells infiltrating the dermis were histiocytic by light microscopy, marker studies, and electron microscopy. Similar cells were present in a bone marrow biopsy specimen. A diagnosis of true histiocytic lymphoma was made. The case illustrates some of the problems that may arise in evaluation of clinical and pathologic findings in a patient with a proliferative disorder of histiocytes and demonstrates the contribution that electron microscopy can provide in establishing the diagnosis.

Practicality of molecular studies to evaluate small lymphocytic proliferations in endoscopic gastric biopsies.

Fifteen endoscopic gastric biopsies (GBx) from 12 patients with small lymphocytic infiltrates morphologically raising a differential of indeterminate lymphocytic infiltrate versus mucosa-associated lymphoid tissue (MALT) lymphoma were analyzed genotypically after frozen-section identification of the abnormal lymphocytic infiltrate. Frozen-section immunoperoxidase immunophenotyping was equivocal in each case. All patients had abdominal pain attributable to superficial gastric ulceration, most often antral, without peripheral lymphadenopathy or hepatosplenomegaly. Rearrangement of the immunoglobulin heavy-chain gene (JH-R, seven patients) or kappa light-chain gene (JK-R, eight patients), was found in eight GBx from eight (seven stage IAE; one stage IBE) of 12 patients, establishing, in conjunction with the histologic features, a diagnosis of low-grade B-cell lymphoma. This diagnosis had not been tenable on multiple prior GBx, ranging from one to five per patient, over intervals of 1 month to 6.5 years (median 4.5 months). The T-cell receptor beta-chain gene retained germline configuration in all cases. Insufficient DNA for molecular studies was extracted from the GBx of two patients, one with JK-R (JH-G) on subsequent GBx and one without further GBx. One patient had two GBx, each demonstrating a single additional band in HindIII digests hybridized with the JH probe. No rearrangements were detected in either the BamHI or the EcoRI digests. Uninvolved tissue from this patient was not available for the exclusion of restriction fragment length polymorphism. Three GBx (two patients) showed germline JH genes (JH-G). One had a partial gastrectomy (histology: MALT lymphoma) in 1981 followed by GBx in 1983 (histologically benign) and in 1990 (JH-G), and negative esophagogastroduodenoscopy (EGD) in 1991 without biopsy. The other patient (two GBx with JH-G) had multiple subsequent abnormal EGD, but no biopsies since December 18, 1990. Adequate DNA for gene rearrangement studies can be extracted from GBx samples weighing as little as 20 mg. The two samples with insufficient DNA weighed 1 and 16 mg, respectively. Practically speaking, the remainder of a frozen block from a single GBx is adequate, thus allowing the screening of multiple endoscopic GBx by sequential frozen sections to determine which one contains the most extensive lymphocytic infiltrate for molecular study. Consistent results are obtained on samples weighing 40 to 60 mg. This method is a suitable alternative to kappa/lambda frozen-section immunoperoxidase immunostaining, which can be uninterpretable on endoscopic biopsies or small biopsies from other sites.

Progressive transformation of germinal centers: comparison of 23 pediatric patients to the adult population.

Approximately 10% of enlarged lymph nodes showing reactive follicular hyperplasia (RFH) will contain one or more progressively transformed germinal centers (PTGC). Comparison of 23 patients 16 yr old and younger (the pediatric group) of age to the adult population (greater than 16 yr old) indicates that most of the patients in each category present with a solitary asymptomatic enlarged lymph node (63% each group), usually cervical, and, while there may be recurrent lymphadenopathy showing RFH with PTGC (RFH/PTGC), evolution to Hodgkin's disease (HD) or other lymphomas is rare. Cases of PTGC unassociated with HD comprise the largest group: 70% (16/23 patients) of pediatric group; 60% (52/87 patients) of adult group. Five pediatric patients (22%) had antecedent HD (four males with lymphocytic predominance-nodular, NL&H HD; one female with nodular sclerosis, NSHD); this group is too small for comparison with adults. One patient (4%) subsequently developed NL&H HD; one patient had concurrent PTGC in the lymphoid rim surrounding NL&H HD. The 23 pediatric patients ranged from 4 to 16 yr (median 11, mean 11.3) with a male predominance (18 M, 5 F) similar to the adult population. Three differences occur comparing PTGC patients without associated HD from the two age groups. The less than or equal to 16 age group has a higher recurrence rate of PTGC (50 versus 23%); two or more biopsies showing PTGC after the initial biopsy was common, 19 versus 0%; and, morphologically, the pediatric cases unassociated with HD more often contain epithelioid histiocytic clusters (44 versus 0%), which may rim the PTGC.(ABSTRACT TRUNCATED AT 250 WORDS)

Pheochromocytoma.

The cytoplasmic granules in an adrenal pheochromocytoma were predominantly ovoid with loose-fitting limiting membranes and eccentrically positioned dense cores. The occurrence of similar granules in a recurrent tumor involving the organ of Zuckerkandl in a second patient suggests that the latter tumor should be designated an extraadrenal pheochromocytoma.

Discordant bone marrow involvement in diffuse large-cell lymphoma: a distinct clinical-pathologic entity associated with a continuous risk of relapse.

From 1975 to 1988, 50 patients with lymph node biopsy-documented diffuse large-cell lymphoma (DLCL) presented with bone marrow involvement. Twenty-four patients (48%) had large-cell lymphoma (LCL) in the bone marrow and were compared with 19 (38%) patients who had small cleaved-cell lymphoma (SCCL) in the marrow. Additionally, seven patients (14%) had mixed small- and large-cell lymphoma (ML) in the marrow. Patients who had LCL marrow involvement were younger (P less than .02) and more frequently had elevated lactic dehydrogenase (LDH) levels (P less than .001), high tumor burden (P less than .01), and more sites of extranodal disease (P less than .05) than those with SCCL in the marrow. The complete response (CR) rate to multiagent chemotherapy was 16.7% in the LCL group and 89.4% in the SCCL group (P less than .001). One third of the patients with LCL in the marrow developed CNS involvement, compared with only one patient in the SCCL group (P = .06). Overall 5-year survival was 79% in patients with SCCL marrow involvement, compared with only 12% in patients with LCL in the marrow (P = .002). Despite a high CR rate, patients with marrow involved by SCCL were at a high continuous risk of relapse with only a 30% failure-free survival at 5 years. We conclude that bone marrow involvement with LCL predicts for extremely poor prognosis with low response rate and short survival. Patients with SCCL in the bone marrow have a high rate of CR and a high rate of 5-year survival; however, there is a high risk of late relapse, and only 15% are in a continuous remission at 8 years.

Clinical implications of nodal reactive follicular hyperplasia in the elderly patient with enlarged lymph nodes.

In older persons, the humoral immune response, as reflected morphologically by proliferation and expansion of germinal centers, is relatively subdued in comparison with the florid reactive follicular hyperplasia (RFH) which may be observed in younger age groups. The presence of RFH in lymph node biopsies in patients 60 yr or older, which we have regarded with concern since 1972, appears to represent an imbalance of the immune system, in some patients, on the background of which predominantly non-Hodgkin's malignant lymphoma (NHL) may be present or will develop. Fifty-eight patients 60 yr old or more who presented with enlarged lymph nodes exhibiting inappropriate RFH for age were identified during the interval from 1969 to 1989. An apparent etiology was initially identified for the reactive follicular hyperplasia in only 12 cases: five with documented rheumatoid arthritis; one each with a history of trauma, positive monospot test, and combination of thrombophlebitis and fungal skin infection, and two each with elevated Epstein-Barr virus (EBV) titers and human immunodeficiency virus type 1 (HIV-1) seropositivity. While most were alive or died of nonlymphomatous causes and one was lost to follow-up, 18 (31%) patients either had concurrent lymphoma or subsequently developed diffuse NHL. There were ten diffuse interfollicular (I-Foll) lymphomas (six concurrent), two diffuse mixed cell lymphomas (DMCL), one diffuse large cell lymphoma (DLCL), one diffuse immunoblastic sarcoma (DIBS), two diffuse small noncleaved cell lymphomas (DSNCL), one unclassified NHL, and only one Hodgkin's disease.(ABSTRACT TRUNCATED AT 250 WORDS)

The value of immunophenotyping on paraffin sections in the identification of T-cell rich B-cell large-cell lymphomas: lineage confirmed by JH rearrangement.

Immunophenotyping of lymphomas using paraffin-embedded lymphoid tissue, not previously distorted by frozen section, is useful in identifying the large neoplastic B cells that may be in the minority in T-cell rich B-cell lymphoma (TCRBCL). Even in cases in which frozen tissue sections are available, the improved morphology in unfrozen sections allows the proper classification of these lymphomas as large cell and identifies their B-cell lineage, which is important for clinical therapeutic studies. Seven cases initially believed to be diffuse mixed cell lymphoma of possible peripheral T-cell lineage showed the large cells to be immunoreactive with L-26 (pan B-cell marker) with the majority of smaller lymphocytes immunoreactive for UCHL-1 and Leu-22 (pan T-cell markers). K/lambda immunostaining on frozen sections was equivocal. In these cases, the diagnosis of large-cell lymphoma of B-cell lineage was confirmed by detection of immunoglobulin heavy- (all seven cases) and light- (six of seven cases) chain gene rearrangements, with germ-line configuration of the T-cell receptor beta-chain gene (all cases). Some cases of TCRBCL may not show detectable rearrangement of the immunoglobulin genes because of the low concentration of neoplastic cells in the samples submitted. The presence of rearrangements in these seven cases, however, supports the diagnosis of TCRBCL based on paraffin immunophenotyping when frozen tissue is not available or when molecular studies are not feasible. Although these seven cases are classified as large-cell lymphoma, an intermediate-grade lymphoma, the influence of the reactive T-cell population on the clinical behavior will require follow-up studies.

Contextual diagnosis of Hodgkin's disease and non-Hodgkin's lymphoma.

The pathologic evaluation of microscopic slides from patients with possible HD or NHL must be performed in the context of complete chronology of the patient's history. Advances in flow cytometry (S-phase analysis), immunophenotyping, and molecular genetics may be of value in diagnosis, classification, and prognostication. The Rye modification of the Lukes-Butler classification of HD has been stable since 1966 and is widely accepted because of its proven reliability. By contrast, the proliferation of classifications of NHL since 1966 speaks for imperfection, partially due to the still incomplete understanding of this diverse group of lymphoreticular malignancies. Successive classifications have incorporated immunologic relationships and concepts and added a clinically significant grading system. A goal of the working formulation was to allow translatability between classifications in the interest of comparison and communication of clinical and research results. Knowledge of the patterns of involvement and spread by HD and by the different categories of NHL helps to narrow the differential diagnosis of radiologic findings. An awareness of the benign, reactive processes and nonlymphoreticular malignant neoplasms that mimic HD and NHL is essential to avoiding misdiagnosis.

Lymphoreticular disease masquerading as or associated with an inguinal or femoral hernia.

Twelve patients (eight men and four women) had previously undiagnosed lymphoreticular disease associated with or simulating an inguinal (nine) or femoral (three) hernia. The disease was present on the left side in eight. Four patients (three women and one man) did not have an actual hernia. Two of these women had a preoperative diagnosis of femoral hernia. Seven of the patients, including all of the women, had non-Hodgkin's lymphoma (three diffuse large cell, two follicular mixed cell and two follicular small cleaved cell) and one patient had lymphocytic predominance (nodular lymphocytic and histiocytic) Hodgkin's disease. No stage predominated. Inguinal lymph nodes from two patients showed, histologically, Kaposi's sarcoma and type I human immunodeficiency virus (HIV) associated disease. Each patient was homosexual and HIV seropositive. Changes suggestive of viral cause were present in the lymph node of one patient. The enlarged lymph nodes of the 12th patient showed stellate suppurative granulomas containing cat-scratch bacilli demonstrated by Warthin-Starry stain. Because of the special processing needs for lymphoreticular diseases and potential for misdiagnosis, surgeons, clinicians and pathologists should be aware of the spectrum of lymphoreticular processes occurring in lymph nodes associated with or masquerading as a hernia, particularly in women.

Differentiation of T-cell lymphoma from Hodgkin's disease. Mitotic rate and S-phase analysis.

Flow cytometric DNA and proliferative compartment (S + G2M) analysis was performed on lymph nodes from 37 patients with Hodgkin's disease (HD) and on 16 lymph nodes plus 6 extranodal biopsies from 22 patients with peripheral T-cell lymphomas (PTCLs). The mitotic rate per 20 high-power fields (HPFs) was also determined for each case. The PTCLs showed significantly higher proliferative activity than the HD cases, as evidenced by a mean S + G2M of 12.0% versus 5.0% for HD and a median mitotic rate of 27 versus 5 mitoses per 20 HPFs in the HD cases. Because morphologic distinction, particularly of mixed cellularity HD (HDMC), from the diffuse small cleaved cell (DSCCL) or mixed cell (DMCL) pattern of PTCL may at times be difficult, these subgroups were compared separately. The 2 cases of DSCCL plus 12 of DMCL yielded a higher proportion of S-phase cells than the 9 HDMC cases with S + G2M means of 9.9% versus 3.3% and a higher mitotic rate, median 21 versus 7 per 20 HPFs. These findings suggest that S-phase determination and mitotic rate provide additional parameters in discriminating PTCL from HD in the most histologically similar cases.