Distinct Histological Variant Research Articles

Cutaneous Balloon Cell Dermatofibroma (Fibrous Histiocytoma)

Dermatofibroma (DF) or cutaneous fibrous histiocytoma is a common benign skin tumor that exhibits multiple, distinct histologic variants. Although clear cell DF has been described in the literature, balloon cell degeneration causing a clear cell DF phenotype has been not been reported to date. Herein, we describe the clinicopathologic findings of balloon cell DF arising on the heel of a 43-year-old man. Clinically, it presented as enlarging tan-white, ulcerated, firm 1.5 cm nodule, clinically suspected to be pyogenic granuloma. Excisional biopsy revealed a circumscribed fibrous tumor populated by mostly clear and spindle cells. A zonal arrangement separated the varied tumor cells where the most superficial, polypoid area showed large, clear polygonal balloon cells; the mid-dermal zone demonstrated a transition between balloon cells, epithelioid cells, and spindle cells; and the deep dermal zone had storiform arrangement of spindle cells, with the fascicles separated by coarse collagen bundles. A CD10+ > CD68+ > Factor XIIIa+ immunophenotype was identified with negative immunolabeling for S-100 protein, HMB-45, cytokeratin AE1/AE3, desmin, smooth muscle actin, lysozyme, and leukocyte common antigen (LCA). Ultrastructurally, the clear tumor cells were filled with multiple, empty, nonmembrane bound vacuoles of varying size. No recurrence has been described after complete excision and 7 months of follow up. DF with balloon cell change, likely secondary to persistent irritation, should be added to the differential diagnosis of cutaneous primary and metastatic neoplasms showing balloon cell degeneration such as balloon cell melanocytic nevi and renal cell carcinoma, respectively.

Intestinal type adenocarcinoma: a previously unrecognized histologic variant of ductal carcinoma of the pancreas

Adenocarcinomas with intestinal differentiation have been described in a wide variety of anatomical sites. To our knowledge, however, ductal adenocarcinomas with intestinal phenotype have not been described in the pancreas. We report here 11 ductal carcinomas of the pancreas that were morphologically similar to colonic adenocarcinomas. These pancreatic carcinomas of intestinal type represented 10% of 110 consecutively removed ductal carcinomas of the pancreas. All intestinal type carcinomas expressed cytokeratin 7, carcinoembryonic antigen, CDX2, and MUC2. The pattern of reactivity of cytokeratin 7 and carcinoembryonic antigen was diffuse, whereas that of mucin 2 staining and CDX2 nuclear labeling was focal and confined predominantly to goblet cells and less frequently to columnar cells. Six carcinomas contained collections of endocrine cells admixed with the columnar and goblet cells. Five carcinomas were associated with high-grade pancreatic intraepithelial neoplasia of intestinal type. Six patients were female and 5 were male. Their ages ranged from 52 to 76 years (mean age, 61 years). The clinical presentation did not differ from that of the conventional ductal carcinomas. All carcinomas originated in the head of the pancreas, and 5 had metastasized to the regional lymph nodes at the time of surgical resection. Only 1 patient survived 5 years. Three patients are disease free from 2.8 to 8.9 months after surgery. Six patients died as a direct result of the carcinomas, and 1 was lost to follow-up. More studies are needed to determine the biologic behavior of this distinctive histologic variant of ductal adenocarcinoma of the pancreas.

A Working Group Classification of Focal Prostate Atrophy Lesions

Focal atrophy is extremely common in prostate specimens. Although there are distinct histologic variants, the terminology is currently nonstandardized and no formal classification has been tested for interobserver reliability. This lack of standardization hampers the ability to study the biologic and clinical significance of these lesions. After informal and formal meetings by a number of the authors, focal atrophy lesions were categorized into 4 distinct subtypes as follows: (i) simple atrophy, (ii) simple atrophy with cyst formation, (iii) postatrophic hyperplasia, and (iv) partial atrophy. In phase 1 of the study, pathologists with varying levels of experience in prostate pathology were invited to view via the Internet a set of "training" images with associated descriptions of lesions considered typical of each subtype. In phase 2 of the study, each participant provided diagnoses on a series of 140 distinct "test" images that were viewed over the Internet. These test images consisted of the 4 subtypes of atrophy and images of normal epithelium, high grade prostatic intraepithelial neoplasia, and carcinoma. The diagnoses for each image from each pathologist were compared with a set of "standard" diagnoses and the kappa statistic was computed. Thirty-four pathologists completed both phases of the study. The interobserver reliability (median kappa) for classification of lesions as normal, cancer, prostatic intraepithelial neoplasia, or focal atrophy was 0.97. The median kappa for the classification of atrophy lesions into the 4 subtypes was 0.80. The median percent agreement with the standard diagnosis for the atrophy subtypes were: simple 60.6%, simple with cyst formation 100%; postatrophic hyperplasia 87.5%; partial atrophy 93.9%. The lower percentage for simple atrophy reflected a propensity to diagnose some of these as simple atrophy with cyst formation. Seven pathologists completed the phase 2 analysis a second time, and their intraobserver reproducibility was excellent. Three of 4 pathologists with low agreement with the standard diagnosis for simple atrophy improved their scores after repeating the analysis after re-examination of the "training set" of images. In conclusion, these criteria for variants of focal prostate atrophy may facilitate studies to examine the relation between various patterns of prostate atrophy and prostate cancer.

Rosetoid schwannoma (neuroblastoma‐like) in association with an anetoderma

We report an additional case of an extremely uncommon but distinctive histological variant of benign schwannoma, which was previously designated as neuroblastoma-like schwannoma by Goldblum et al. A 29-year-old woman referred to a 6-year-history of an atrofic macule. Its clinical appearance was similar to that of an anetoderma. A cutaneous biopsy showed findings consistent with a neuroblastoma-like schwannoma with the following peculiar features: (i) Being fully composed of rosette-like structures. (ii) Association to an anetoderma. Because neither the histological pattern nor the type of tumor allows a differential diagnosis with neuroblastoma, we propose the descriptive term of rosetoid schwannoma. And to our knowledge, this will be the first case reported of rosetoid schwannoma associated to anetoderma.

Cutaneous melanoma with pseudomyxoid features

A 96-year-old man presented with a polypoid melanoma, which showed a prominent clear stroma, similar to that of myxoid melanoma, but stained negative for Alcian blue at pH 2.5 and for colloidal iron. It is not clear whether melanoma displaying pseudomyxoid features (pseudomyxoid melanoma) may represent a distinct histological variant of melanoma. However, it must be differentiated from true myxoid melanomas, in which Alcian blue-positive acid mucopolysaccharides are present. Urso C. Cutaneous melanoma with pseudomyxoid features.

Clinical curiosity: Cribriform‐morular variant of papillary thyroid carcinoma

There is an increasing awareness of the association of papillary thyroid carcinoma and familial adenomatous polyposis (FAP). Although the incidence is rare, most tend to occur in women. Several authors have described a distinctive histologic variant of papillary thyroid carcinoma, the cribriform-morular variant, which is associated with FAP but also may be encountered in patients with non-FAP. This diagnosis may precede the symptoms of colorectal polyposis. A healthy 36-year-old woman was seen with a left thyroid nodule, and a 34-year-old woman with FAP was seen with a right thyroid nodule; both masses were suspicious for papillary thyroid carcinoma. Both patients underwent total thyroidectomy. Pathologic examination of both specimens revealed papillary thyroid carcinoma, cribriform-morular variant. The first patient subsequently underwent colonoscopy, which was negative for polyposis. Patients diagnosed with the cribriform-morular variant of papillary thyroid cancer should be screened for the presence of FAP.

An Unusual Case of Floor of Mouth Swelling: Case Report, Differential Diagnosis and a Review of the Literature

The oral cavity is an uncommon site for a true lipoma. A distinct histological variant is the spindle cell lipoma. This is a rare oral lesion. A case of an intra-oral spindle cell lipoma in a 55-year-old female is reported, a differential diagnosis is presented and the histopathology is discussed. An oral swelling is a common presenting complaint and requires further investigation.

A case of spindle cell lipoma arising in the tongue

Spindle cell lipoma (SCL) is a distinct histological variant of lipoma, characterized by replacement of mature fat cells by collagen-forming spindle cells. We report a case of SCL that arose in the tongue of a 75-year-old Japanese man. Immunohistochemical analysis revealed that the spindle cells expressed CD34, bcl-2, and vimentin. Interestingly, the tumor cells exhibited strongly positive immunoreactivity for cyclin-dependent kinase 4 (CDK4). Since it has already been reported that CDK4 is not expressed in ordinary lipomas but expressed in almost all cases of liposarcoma, the positive immunoreactivity for CDK4 in the present case suggests that SCL has a character that is distinct from ordinary lipoma.

Cutaneous Leiomyoma with Cytologic Atypia, Akin to Uterine Symplastic Leiomyoma

BACKGROUND Smooth muscle tumors of the skin with cytologic pleomorphism and mitotic activity have traditionally been characterized as leiomyosarcomas, despite having a benign clinical course. In the uterus, there is a smooth muscle tumor known as symplastic leiomyoma, which typically has cytologic pleomorphism without significant mitotic activity. OBJECTIVE The objective was to illustrate by case report the unusual histologic variant of the cutaneous pilar leiomyoma analogous to the symplastic leiomyoma of the uterus. METHODS A 54-year-old woman presented with a clinical picture of cutaneous leiomyoma but had histologic features of nuclear hyperchromasia and pleomorphism, but rare mitoses. RESULTS Management of this patient included excision of the involved area. CONCLUSION Symplastic leiomyoma is an atypical uterine leiomyoma with cytologic atypia. We present the case of a patient with cutaneous leiomyomas that histologically demonstrated similar features to a uterine symplastic leiomyoma. We believe that this represents a distinct histologic variant of the cutaneous pilar leiomyoma analogous to the symplastic leiomyoma of the uterus.

Invasive micropapillary salivary duct carcinoma: a distinct histologic variant with biologic significance.

An invasive micropapillary component has been described in tumors of several organs and is nearly always associated with aggressive biologic behavior. We present 14 cases of salivary duct carcinoma (SDC) with an invasive micropapillary component (invasive micropapillary SDC) and compare the clinicopathologic findings of these cases with those of cases of conventional SDC. The mean age of the 14 patients (10 men, 4 women) was 65.8 years (range, 26-80 years). The mean size of the tumors was 2.4 cm (range, 1.3-5 cm). The parotid gland was involved in 12 patients and the submandibular gland in 2. Histologically, all tumors had an invasive micropapillary architecture admixed with features typical for SDC. Invasive micropapillary carcinoma was characterized by morula-like small cell clusters without fibrovascular cores, surrounded by a clear space. Tumor cells exhibited moderate- to high-grade nuclear features, conspicuous nucleoli, and eosinophilic cytoplasm. This component was distributed diffusely in 9 tumors and focally in 5. Angiolymphatic and perineural invasion was seen in all tumors. A residual pleomorphic adenoma was detected in four tumors. Of the 12 tumors examined, all were diffusely positive for cytokeratin 7 and epithelial membrane antigen (with a distinctive "inside-out" pattern) but negative for cytokeratin 20. Tumors were frequently immunoreactive for BRST-2 (gross cystic disease fluid protein-15) and androgen receptor protein. Aberrant expression of HER-2/neu or p53 was detected in seven tumors each. The mean Ki-67 labeling index was 33.1% (range, 6.3%-61.6%). All 14 patients with invasive micropapillary SDC had cervical or periglandular lymph node metastasis, and this value was significantly higher than for conventional SDCs. Local recurrence developed in 4 patients and distant metastatic disease in 9. Clinical follow-up (mean, 25.5 months) was available for 13 patients: 9 died of disease within 24 months after the diagnosis (mean, 17.6 months), 1 was alive with metastatic disease at 19 months, and 3 were free of disease. Overall survival of these patients with invasive micropapillary SDC was significantly shorter than that of patients with conventional SDC (n = 49) in our series (P = 0.031). Our results suggest that invasive micropapillary SDC is a distinct, aggressive variant of SDC, with a propensity for extensive lymph node metastasis and rapid disease progression.

Cribriform-Morular Variant of Papillary Thyroid Carcinoma: Ultrastructural Study and Somatic/Germline Mutation Analysis of the APC Gene

Cribriform-morular variant of papillary carcinoma is a distinctive histological variant of thyroid cancer, characterized by intermingled cribriform, follicular, papillary, trabecular, and morular architecture. These tumors are known to be associated with familial adenomatous polyposis (FAP), but are also encountered in non-FAP patients. The authors report on ultrastructural and genetic studies of 3 patients with this type of carcinoma-associated FAP. There were numerous microfilaments approximately 100 nm long at the nuclear clearing area of the morular regions. Two of the 3 patients showed germline APC mutations, and 1 had so somatic APC mutation. Both mutations were in previously unreported regions. The study provides new information for understanding the development of this rare tumor.

Correlation of the WHO schema for the classification of thymic epithelial neoplasms with prognosis: a retrospective study of 90 tumors.

A series of 90 thymic epithelial tumors were reviewed and classified by histopathologic characteristics into the three major categories (A, B, and C) recognized by the WHO schema. Each tumor type was correlated with patient characteristics and clinical data (age, sex, presence of myasthenia gravis, tumor size and invasiveness, and completeness of resection), and with outcome (survival, recurrence, and metastasis). All tumors were categorized by the WHO schema. Myasthenia gravis was present in 32 patients, mostly young and with type B thymic epithelial tumors. Tumors were invasive in 56% of cases, but resection was total in 67% of patients and only partial in the rest. Five factors were shown by univariate analysis to be associated with a favorable prognosis: presence of myasthenia gravis (p = 0.0389), younger age (p = 0.0022), completeness of resection (p = 0.0001), noninvasiveness (p = 0.0138), and tumor type A or B, as opposed to type C (p = 0.0001). Prognosis for types A and B was not significantly different, suggesting that the subtypes of types A and B thymic epithelial tumors should be regarded as a morphologic continuum rather than as distinct histologic variants.

Prostatic foamy gland carcinoma with aggressive behavior: clinicopathologic, immunohistochemical, and ultrastructural analysis.

Foamy gland carcinoma is a recently described histologic variant of prostatic adenocarcinoma characterized by abundant foamy cytoplasm and minimal cytologic atypia. The biologic behavior and biochemical nature of the foamy adenocarcinoma cells are unknown. Six cases of prostatic adenocarcinoma with marked foamy appearance were identified from radical prostatectomies. Clinicopathologic, histochemical, immunohistochemical, and ultrastructural analyses were conducted. The patients ranged in age from 50 to 73 years (mean age, 65 years) with preoperative serum prostate-specific antigen levels ranging from 2.7 to 37.5 ng/mL (mean, 15.2 ng/mL). All six cases were bilateral high-volume tumors. Five of six patients had high-grade tumors with extraprostatic extension. The foamy tumor cells were negative for mucin and lipid stains, but were positive for colloidal iron and Alcian blue stain. Ultrastructurally, the foamy cells displayed numerous intracytoplasmic vesicles and numerous polyribosomes. The authors conclude that the foamy appearance of these tumor cells is the result of the presence of numerous intracytoplasmic vesicles, and not the result of the presence of lipid or neutral mucin. This study illustrates that foamy gland carcinoma is a distinctive histologic variant of prostatic adenocarcinoma and is often associated with an aggressive behavior despite its deceivingly benign histologic appearance.

Anaplastic carcinoma of the colon: clinicopathologic study of eight cases of a poorly recognized lesion.

Eight cases of a distinctive histological variant of bowel cancer characterized by an anaplastic morphology were identified from 2,650 colonic malignancies (0.3%). The tumors were histologically composed of sheets of anaplastic tumor cells with frequent atypical mitoses, absence of gland formation, and mucicarmine and periodic acid-Schiff (PAS) negativity. Positive immunostaining for cytokeratin and vimentin was observed in eight cases and for epithelial membrane antigen in three; whereas carcinoembryonic antigen, alpha-fetoprotein, S-100 protein, HMB-45 antimelanoma antigen, leukocyte common antigen, and neuroendocrine markers were uniformly negative. Ultrastructural examination demonstrated intercellular tight junctions, focal surface microvilli, and apical terminal webs or long rootlets of microfilaments supporting a colonic derivation. At the time of diagnosis, metastases to regional lymph nodes were found in seven cases and to the liver in six. All patients in this study died of tumor within 9 months. This report emphasizes a poorly recognized variant of colonic carcinoma, characterized by a high degree of anaplasia and malignant behavior. The differential diagnosis for these lesions is discussed.

Hyalinizing Spindle and Epithelioid Cell Nevus

Five cases are described of a distinctive histologic variant of benign spindle and epithelioid cell nevus characterized by extensive and prominent stromal hyalinization. The lesions consisted of a proliferation of spindle or epithelioid nevocytes scattered singly or in small clusters in the dermis and surrounded by abundant paucicellular hyalinized or collagenous stroma. Three patients were men and two were women. Their age range was 23 to 45 years (mean, 32). Two of the lesions were located in the head and neck region, two in the lower extremities, and one in the trunk. Immunohistochemical strains showed positive staining of the spindle or epithelioid cells with S-100 protein and vimentin; stains for keratin, EMA, CEA, actin, and desmin were all negative. Van Gieson and trichrome histochemical reaction demonstrated the collagenous nature of the hyalinized intercellular matrix; Congo red, crystal violet, and alcian blue stains were all negative. The etiology and pathogenesis of the intercellular hyalin deposits are unknown, but they probably represent a regressive phenomenon in longstanding or involuting lesions. Hyalinizing Spitz nevus must be included in the differential diagnosis of cutaneous lesions exhibiting a prominent hyalinized stroma and must be differentiated from other dermal neoplasms, particularly cutaneous metastases from occult internal malignancies and malignant melanoma.

The clinicopathological correlation of epithelial subtyping in thymoma: A study of 112 consecutive cases

The clinicopathological features of 112 thymomas collected from the surgical pathological files of Taipei Veterans General Hospital from 1961 to 1991 were investigated to determinate the clinical efficacy of epithelial subtyping. All thymomas were categorized based on the Müller-Hermelink system into three subtypes: cortical thymoma, mixed thymoma, and medullary thymoma. The former was further subclassified into organoid thymoma, conventional cortical thymoma, and well differentiated thymic carcinoma (WDTC) according to the systems of Pescarmona and Kirchner. The association of each subtype with sex, age at diagnosis, clinical stage, presence of myasthenia gravis, and length of survival was studied. As classified by the Müller-Hermelink system, the cortical thymomas as a whole tended to occur in younger patients and were more frequently associated with myasthenia gravis than the medullary thymomas. The cortical thymomas also showed a propensity to be invasive in nature, whereas the medullary thymomas generally behaved as benign tumors. Further subclassification of cortical thymomas into organoid thymoma, conventional thymoma, and WDTC did not provide more information about clinical behavior. By Kaplan-Meier's actuarial survival analyses none of the epithelial subtypes displayed a statistically significant influence on prognosis. It is concluded that staging remains the most important factor affecting the patient's outcome. Because of the existence of many intermediate forms and the deficiency of clinical relevance, the subclassification of cortical thymomas should be interpreted as a morphological continuum rather than as distinct histological variants.

Peripheral T-Cell Lymphomas: Histologic, Immunohistologic, and Clinical Characterization

A review of 40 cases of peripheral T-cell lymphoma identified at our institution between March 1983 and December 1985 revealed a clinically, histologically, and immunologically diverse group of neoplasms that were difficult to classify by conventional histomorphologic criteria for non-Hodgkin's lymphomas. These lymphomas were frequently extranodal at the time of initial manifestation (52%), and their clinical aggressiveness correlated with three major histologic categories--small lymphocytic, diffuse mixed, and large cell. Of the 40 lymphomas, 18 exhibited distinctive histologic features that allowed assignment of these cases into one of four subgroups: (1) angioimmunoblastic lymphadenopathy, (2) lymphomatoid granulomatosis, (3) Hodgkin's-like disease, and (4) Lennert's lymphoma (lymphoepithelioid lymphoma). Study of all our cases that fulfilled the morphologic criteria for lymphomatoid granulomatosis or angioimmunoblastic lymphadenopathy by using immunologic methods for identification of B-cell and T-cell antigens has shown these neoplasms to be peripheral T-cell lymphomas. Therefore, we now consider these earlier proposed entities to be distinct histologic variants of peripheral T-cell lymphoma.

Sarcomatoid Renal Carcinoma

AbstractSarcomatoid renal carcinoma made up 1 per cent of renal parenchymal tumors resected from 1967 to 1980. The majority of patients with this aggressive type of renal carcinoma were symptomatic and had a palpable renal mass at the time of diagnosis. Only 2 of 13 patients had tumor confined within the renal capsule at the time of operation. One of these patients survived and 12 of 13 died rapidly of metastatic renal carcinoma, with a median survival of 6.3 months from the time of diagnosis. This distinctive histologic variant of renal carcinoma has a highly malignant biological behavior and, as effective adjuvant treatment for renal carcinoma becomes available, should be one of the tumor types treated vigorously.