Silloo B. Kapadia

Basaloid squamous cell carcinoma of the head and neck: A clinicopathologic and flow cytometric study of 10 new cases with review of the English literature

INTRODUCTION We describe the clinicopathologic and flow cytometric features of 10 cases of basaloid squamous cell carcinoma (BSCC) of the head and neck to determine if DNA ploidy is a useful prognostic indicator. We also provide a review of 80 cases previously reported in the English language literature. MATERIALS AND METHODS The 10 cases were obtained from the surgical pathology files of Presbyterian University Hospital and The Eye and Ear Institute, Pittsburgh, PA (1987-1991). In all 10 cases, the microscopic slides and clinical data were reviewed. Flow cytometry was performed using the Hedley technique and formalin-fixed, paraffin-embedded tissue. RESULTS The mean age of patients with BSCC was 64 years (range, 49 to 75 years). Tumor involved the base of tongue (n = 5), hypopharynx-epiglottis (n = 3), and tonsil (n = 1). One case presented with cervical lymph node metastasis from an unknown primary site. Histologically, BSCC showed a biphasic pattern with basaloid-squamous elements, comedonecrosis, stromal hyalinization, surface dysplasia, and an in situ and/or invasive squamous cell carcinoma component. Flow cytometry revealed six diploid and four aneuploid tumors. Five of six patients with diploid and all four patients with aneuploid tumors developed early regional and/or distant metastases. Of the two patients who died of disease, one had a diploid and the other an aneuploid tumor. CONCLUSION Our study reaffirms the predilection of BSCC for the base of tongue, pyriform sinus, and supraglottic larynx, and its aggressive biologic behavior with a high incidence of cervical lymph node metastasis (64%), distant spread (44%), and death from disease (38% mortality at 17 months median follow-up). However, in contrast to previous reports, tumor ploidy by flow cytometry provided no additional prognostic information beyond that supplied by routine histologic evaluation.

Primary lymphoma of waldeyer's ring clinicopathologic study of 68 cases

The clinical and pathologic findings were studied in 68 patients with primary lymphoma of Waldeyers ring (WR). The initial sites included: tonsil (51%; 9% bilateral), nasopharynx (35%), base of tongue (9%), and multiple areas (4%). The mean age was 58 years, with a male to female ratio of 1.1:1.0. Tonsillar and base of tongue lesions presented with sore throat and dysphagia, whereas nasopharyngeal lymphomas most commonly presented with nasal, auditory, and cranial nerve sympatomatology. A neck mass was the sole presenting symptom in 12% of patients. Work‐up showed 42% Stage I, 47% Stage II, 4% Stage III, and 7% Stage IV. All were non‐Hodgkins lymphomas. Diffuse architecture predominated (71%) and 70% had a histiocytic or large cell morphology (diffuse histiocytic 51%, nodular histiocytic 19%). The National Cancer Institute (NCI) Working Formulation grades were 13% low, 81% intermediate, and 6% high. In difficult cases, detection of monoclonal immunoglobulin, absence of keratin staining, and lack of epithelial features by electron microscopy were useful adjuncts aiding in diagnosis. Following complete remission, 28 patients relapsed, 75% of these within 2 years (median, 10 months). Thirty‐seven (54%) patients died with disease (median survival, 27 months). Of these, 89% had disseminated lymphoma. Local‐regional disease was the direct cause of death in 13%. Recurrence or persistence of disease in WR occurred in 9% of cases, most with initial clinical evidence of soft tissue extension. Stage I patients had a significantly better median survival (67 months) than Stage II patients (20 months) (P = 0.03). Prognostically favorable histologic parameters included lower NCI Working Formulation grade and follicular architecture. Ten patients (15%) developed extranodal disease, eight involving the gastrointestinal (GI) tract, and all died within 1 year of its occurrence. The findings indicate that stage and certain histologic parameters are important prognostic factors in WR lymphoma. The study confirms the association of primary WR lymphoma with other extranodal disease, particularly involving the GI tract, and emphasizes the poor prognosis of patients in whom this occurs.

Crystal-storing histiocytosis associated with lymphoplasmacytic neoplasms: report of three cases mimicking adult rhabdomyoma

Massive crystal deposition is rare in lymphoplasmacytic (LPc) or plasma cell neoplasms. We report three cases in which the accumulation of crystals in histocytes closely reproduced the histologic features of adult rhabdomyoma. The patients, all female, aged 18, 77, and 78 years, presented with tumor of cervical lymph nodes (two cases) or the otolaryngic mucosa (two cases). In addition, two patients had monoclonal serum or urine immunoglobulin (fgM-k-1, unknown-1), and one had renal and bone marrow involvement on biopsy. This last patient died of acute renal failure at 5 months, another was alive without disease at 8 years, and the remaining one was lost to followup. Lymph nodes, mucosae, and kidney showed a neoplastic LPc infiltrate masked by sheets of large benign histiocytes containing sheaves of crystals. Paraffinsection immunohistochemistry demonstrated monoclonal staining of the LPc cells in all cases (fgM-k-2, IgA-k-1) and of the crystals (IgM-K) in one case. In all patients, the crystal-containing cells were positive for KP-1 (CD68), but not for desmin, muscle-specific action, or myoglobin. These findings suggest that, in any case of adult rhabdomyoma in which the histologic findings are not typical, a crystal-storing histiocytosis should be ruled out: recognition of the atypical LPc component and the histiocytic immunophenotype of the crystal-storing cells will help prevent a serious misdiagnosis.

Neural cell adhesion molecule in adenoid cystic carcinoma invading the skull base

Neural cell adhesion molecules (N-CAMs) are expressed in neuromuscular tissues, neuroblastoma, and small cell lung carcinoma. Adenoid cystic carcinoma may invade the skull by either direct extension or neural involvement, particularly along the second and third divisions of the trigeminal nerve (V2 and V3). Eighteen patients with adenoid cystic carcinoma that invaded the skull base were studied. The tumors were graded into predominantly solid (3), cribriform (11), or tubular-trabecular (4) patterns, and neural involvement was evaluated histologically. Paraffin sections were examined by use of monoclonal antibodies for N-CAM and Ki-67, a proliferation marker, with the avidin-biotin-peroxidase method. Fifteen (83%) tumors showed perineural involvement; in the remaining three cases no nerves were present for histologic examination. Fourteen (93%) of 15 tumors with perineural involvement were reactive with N-CAM. Proliferation, measured by the presence of nuclear Ki-67, was markedly increased in tumors with predominantly solid patterns. We demonstrated that N-CAM is expressed in adenoid cystic carcinoma. The role of N-CAM as a neurodeterminant that facilitates the spread of adenoid cystic carcinoma along nerves, however, remains unanswered and warrants further study.

Induced acute non-lymphocytic leukemia following long-term chemotherapy. A study of 20 cases

Twenty individuals developed acute non‐lymphocytic leukemia (ANLL) following long‐term chemotherapy for other disorders. The primary disorders included non‐Hodgkins lymphoma (five), Hodgkins disease (five), carcinoma (four), multiple myeloma (three), chronic lymphocytic leukemia (two), and rheumatoid arthritis. Leukemia developed from 11–132 months (mean approximately 60 months) following institution of chemotherapy and all cases have occurred since 1974. Pre‐leukemic cytopenias were present in 15 individuals. Fifteen of the 20 patients had chromosome analyses and 14 were abnormal. The leukemia was invariably refractory to chemotherapy with a median survival of only two months. Of the patients autopsied, only one individual had any evidence of the primary malignancy. This study illustrates the need for surveillance for secondary ANLL following long‐term chemotherapy with/ without radiotherapy. Duration of optimal chemotherapy for the primary disease must be determined by control trials and weighed against the risk of developing a secondary leukemia.

The role of p53 mutation and protein expression in primary and recurrent adenoid cystic carcinoma

Adenoid cystic carcinoma (ACC) is a malignant tumor of salivary gland origin having a propensity for spread by direct extension or perineural invasion with frequent recurrences. Previous reports have shown that tumor behavior is not always predicted by histological pattern or stage. Little is known of the role of p53 tumor suppressor gene mutation and altered protein expression with respect to ACC pathobiology and recurrence. The authors analyzed a group of 14 ACC specimens (seven primary; seven recurrent) from 13 patients treated between 1987 to 1993. Formalin-fixed, paraffin-embedded specimens were reviewed and subjected to, immunohistochemistry (p53, DO-7, DAKO, Nutley, NJ; and WAF-I, Ab-1, Oncogene Sciences, Uniondale, NY) on 4-microm-thick histological sections as a prelude to p53 genotyping. In one case, sequential material representing primary and recurrent tumor was analyzed. Each tumor specimen was topographically genotyped for p53 point mutational change. Minute tissue samples were removed from unstained sections, polymerase chain reaction (PCR) amplified for p53 exons 5 to 8, and then underwent direct DNA sequencing. Six of seven primary ACCs were p53 immunostain negative. Four of seven recurrent (57%) ACCs were p53 immunopositive. These tumors showed varying degrees of p53 immunopositivity ranging from diffuse, intense staining of most tumor cells (n = 1) to interspersed, strongly positive cells mixed with predominantly p53 immunonegative cells (n = 4). All tumors were WAF-I immunostain negative. Two of the most immunopositive recurrent tumors each manifested a single type of p53 point mutation detected by p53 DNA genotyping (p53 exon 5:codon 175 and p53 exon 6:codon 199). In the case in which both primary and recurrent tumor was available, only the recurrent tumor contained point mutational damage. Negative immunostaining for p53 in primary ACC suggests that p53 mutation is not important in early events involving development of this tumor. In contrast, the frequent presence of p53-positive cells and the detection of point mutations in recurrent ACC suggests that p53 alterations are involved in later stages of tumor progression, important in the phenomenon of ACC recurrence.

The biology and pathology of selected skull base tumors

This paper describes the pathobiology of some of the more common skull base tumors. In addition to clinicopathologic features, emphasis is placed upon methods of diagnosis utilizing immunoperoxidase stains and molecular markers that may or may not impact upon prognosis.

Chondrosarcoma of the nasal septum: Skull base imaging and clinicopathologic correlation

Chondrosarcoma arising in the head and neck and craniofacial region is an uncommon lesion. The nasal septum is a particularly rare site of origin, with approximately 30 cases previously reported in the English literature. We present six new cases of chondrosarcoma arising in the nasal septum. Each of these tumors required cranial base surgical approaches for removal. Current imaging techniques allow a very accurate diagnosis to be made before biopsy. The characteristic ring-forming calcifications seen on computed tomography scans can be correlated with the histologic pattern of calcification. Magnetic resonance imaging techniques allow precise definition of tumor extent, which is particularly important because the disease is best treated with primary surgery. Advances in imaging and surgical techniques allow a much more complete tumor removal. It is hoped that this will increase the likelihood of cure in these patients. Surgical management and indications for adjuvant therapy are discussed.

Lymphoepithelial carcinoma of the larynx and hypopharynx: study of eight cases with relationship to Epstein-Barr virus and p53 gene alterations, and review of the literature.

Eight cases of lymphoepithelial carcinoma (LEC) of the larynx and hypopharynx were evaluated for clinicopathologic features, and the presence of the Epstein-Barr virus (EBV) and p53 alterations. The seven men and one woman, all of non-Asian descent, averaged 64 years of age. Eighty-eight percent had histologically confirmed cervical lymph node metastasis at diagnosis. None had systemic disease. Seven of eight patients available for follow-up (mean, 17.7 months) were alive and free of disease, although one did develop recurrent tumor in the neck. Four tumors were composed, histologically, of pure LEC. Four others had foci of both LEC and conventional squamous cell carcinoma. All eight tumors exhibited alterations in p53 expression, but none was positive for EBV. Combining these 8 cases with the 15 previously published cases in the English literature indicate that LEC in this site is a rare, rather aggressive tumor, primarily of older adults (mean, 62 years) with a propensity for early cervical lymph node metastasis and eventual distant dissemination and death from disease in about one third of patients. Although p53 alterations are common and of no apparent prognostic significance, LEC at this site seems to have little, if any, relationship to the EBV in patients of non-Asian origin.

Simultaneous occurrence of non‐Hodgkinapos;s lymphoma and acute myelomonocytic leukemia

The simultaneous occurrence of nodular poorly differentiated lymphocytic lymphoma (NLPD) and acute myelomonocytic leukemia (AMML) was confirmed by the histologic examination of lymph node section, peripheral blood, and bone marrow. This association in the absence of previous chemotherapy or radiotherapy has not been previously documented. There have been six previous case reports of patients with non‐Hodgkinapos;s lymphocytic lymphoma who, during treatment with alkylating agents or radiotherapy, developed acute myeloid leukemia (AML). These methods of therapy may have had a leukemogenic role in such patients. The possible relationship between these two diseases is discussed.