Metastatic metaplastic carcinoma of the breast (MCB): an uncharacteristic pattern of presentation with clinicopathologic correlation.

Metaplastic carcinoma of the breast (MCB) is a well recognized but uncommon aberrant manifestation of poorly differentiated invasive carcinoma containing both epithelial (ductal) and mesenchymal elements as well as a transitional form between them. This heterogeneous tumor characteristically contains ductal carcinoma cells mixed with areas of diverse morphologic phenotype displaying spindle, squamous, chondroid, or osseous differentiation. Some studies have suggested that certain types of metaplastic carcinoma have a more favorable prognosis as compared with others. We describe a case involving a 67-yr-old woman who presented with metastatic nodules in the lungs and a vague but recent history of breast cancer. The case highlights a subtype of MCB with a predominant spindle cell component metastatic to the lung. Fine-needle aspiration biopsy (FNAB) smears of the nodules revealed a bland, spindle cell, mesenchymal proliferation with minimal evidence of an epithelial component. A second primary was clinically excluded and a request for review of the original slides identified a metaplastic component to the original tumor with a histologic and immunohistochemical profile identical to the metastatic tumor, confirming origin from the breast. Metaplastic carcinomas of the breast commonly bypass axillary lymph nodes and present as distant metastases. FNAB diagnosis of metaplastic carcinoma of the breast is quite difficult at the primary site and poses a formidable diagnostic challenge at a metastatic site, especially when the dominant pattern is not of the usual type. The literature is reviewed, confirming the rarity of such a presentation and the novelty of this case. Confirmation by FNAB is also quite difficult but may become more commonplace as a trend toward minimal intervention continues to gain popularity. This case emphasizes the importance of recognizing and reporting metaplastic elements in primary breast tumors, as well as the value of direct morphologic comparison of cytologic material from FNABs with archival histologic material. In such situations, the importance of complete and accurate clinicopathologic information is underscored.     

11q13 Allelic Imbalance Discriminates Pulmonary Carcinoids from Tumorlets : A Microdissection-Based Genotyping Approach Useful in Clinical Practice

Pulmonary tumorlets are minute neuroendocrine cell proliferations believed to be precursor lesions to pulmonary carcinoids. Little is known of their molecular pathogenesis because of their small size. Using tissue microdissection, we evaluated 11q13 region allelic imbalance in the pathogenesis of pulmonary tumorlet/carcinoid lesions. The int-2 gene was selected because of its chromosomal location at 11q13 in close proximity to MEN1, a tumor suppressor gene frequently mutated in familial forms of neuroendocrine cancer. Three cohorts of patients were studied: subjects with typical carcinoid tumors and coexisting tumorlets (n = 5), typical carcinoids without tumorlets (n = 6), and tumorlets alone without carcinoid lesions (n = 5). A total of 11 carcinoids and 11 tumorlets were microdissected from 4-micrometer-thick histological sections. Genotyping was designed to detect allelic imbalance of the int-2 gene and involved DNA sequencing of two closely spaced deoxynucleotide polymorphisms. Subjects shown to be informative were evaluated for allelic imbalance in tumorlet/carcinoid tissue. Eight of 11 (73%) carcinoids manifested allelic, in contrast to only one of 11 (9%) of tumorlets. Int-2 allelic imbalance was significantly associated with carcinoid tumor formation (P < 0.01). In patients having both carcinoid tumors and tumorlets, the latter showed allelic balance and were thus discordant in genotype with coexisting carcinoid excluding pathogenesis of tumorlets from intramucosal spread from carcinoid tumors. Int-2 allelic imbalance was shown to be an early event in carcinoid tumor formation by virtue of the absence of allelic imbalance for other common cancer-related gene disturbances involving 11p13 (Wilms' tumor), 3p25 (von-Hippel-Lindau), and 17p13 (p53). Demonstration of 11q13 allelic imbalance by microdissection/genotyping may be a useful discriminatory marker for pulmonary neuroendocrine neoplasia.     

Differential loss of heterozygosity profile on chromosome 3p in ductal and lobular breast carcinomas

The 2 main histologic types of infiltrating breast cancer, invasive lobular and invasive ductal carcinoma, are morphologically and clinically distinct. Studies revealed that different patterns of gene expression and loss of heterozygosity can also distinguish these 2 subtypes. A whole-genome study using single nucleotide polymorphism array found a significantly higher frequency of loss of heterozygosity on 3p in invasive ductal carcinoma when compared with invasive lobular carcinoma. In this study, we performed a loss of heterozygosity analysis of the 3p chromosome region in ductal and lobular breast tumors. Seven microsatellite markers were evaluated in a series of 136 sporadic breast cancer cases (118 invasive ductal carcinoma and 18 invasive lobular carcinoma) and correlated with clinical-histopathologic parameters from the patients. A significantly higher frequency of loss of heterozygosity was observed in invasive ductal carcinoma (65.3%) when compared with invasive lobular carcinoma (38.9%). When the markers were analyzed separately, loss of heterozygosity at 3 of them, D3S1307 in 3p26.3, D3S1286 in 3p24.3, and D3S1300 in 3p14.2, were significantly more frequent in ductal than in lobular tumors. D3S1307 marker showed the highest frequency of loss of heterozygosity in invasive ductal carcinoma (46.2%), and associations between loss of this marker and loss of estrogen and progesterone receptors were found in these samples. Our results confirm the observations that invasive ductal carcinoma has a higher frequency of loss of heterozygosity events across the 3p region than invasive lobular carcinoma and show that specific losses on 3p26.3, 3p24.3, and 3p14.2 regions are more frequent in ductal than in lobular tumors. We discuss our data in relation to the known tumor suppressor genes that are mapped at the 3p loci investigated and their present relevant roles in breast cancer.     

Metastatic metaplastic breast carcinoma mimicking pulmonary squamous cell carcinoma on fine‐needle aspiration

Metaplastic squamous cell carcinoma (SCC) of the breast is a rare type of breast cancer. Metastases to the lung, which can be a major site of second primary tumor development among breast cancer patients, are difficult to distinguish from primary SCC of the lung and present a unique challenge for pathologists. There are few available discriminating immunohistochemical markers as squamous differentiation typically leads to loss of expression of characteristic primary epithelial cell markers of both breast and lung origin. GATA protein binding 3 (GATA‐3) is a useful marker of breast origin in metastatic ductal and lobular carcinomas including poorly differentiated triple‐negative carcinomas and some metaplastic carcinomas. Here, we present a case of metastatic SCC presenting as a solitary lung mass with regional lymph node metastases and a single satellite lesion in a patient with a history of metaplastic SCC of the breast. In addition to the routine markers of squamous differentiation, the metastases were also positive for estrogen receptor (ER) and GATA‐3 on cytologic material obtained by transbronchial FNA. This suggests that immunoreactivity for ER and GATA‐3 may support a diagnosis of metastatic SCC in the context of a prior metaplastic SCC of the breast. Diagn. Cytopathol. 2015;43:844–849. © 2015 Wiley Periodicals, Inc.     

Metastatic ductal carcinoma of the breast to the thyroid gland diagnosed with fine needle aspiration: A case report with emphasis on morphologic and immunophenotypic features

Metastases to the thyroid are uncommon [<0.2% of thyroid fine needle aspirations (FNA)]. Of metastases to the thyroid, breast carcinoma is relatively common. The diagnosis of metastasis to the thyroid has important therapeutic and prognostic implications. To our knowledge, a morphologic and immunophenotypic comparison of metastatic ductal carcinoma of the breast and primary thyroid carcinomas has not been reported. Here, we report the case of a 37‐year‐old female with a history of metastatic ductal carcinoma of the breast (modified Bloom‐Richardson grade 2; ER+, PgR+, HER2+) diagnosed 6 years prior. She developed hoarseness, prompting a CT scan. Multiple thyroid nodules were found, including a 1.5 cm hypoechoic, solid, irregularly‐shaped nodule. On FNA, cells were arranged singly and in crowded groups, varied in size and degree of pleomorphism, and exhibited rare nuclear grooves, inconspicuous nucleoli, and rare intracytoplasmic lumina with no nuclear pseudoinclusions or colloid (Figs. 1A and B). These findings raised the differential of papillary thyroid carcinoma (Fig. 1C), follicular neoplasm (Fig. 1D), medullary carcinoma (Fig. 1E), parathyroid (Fig. 1F), and metastatic breast carcinoma. Immunostaining for GATA‐3 (+), ER (+), PAX‐8 (?), and TTF‐1 (?) was consistent with metastatic breast carcinoma (Fig. 2). We conclude that metastatic breast carcinoma to the thyroid may morphologically mimic primary thyroid carcinoma on FNA; a panel of immunomarkers, such as GATA‐3, hormonal marker(s), PAX‐8, and TTF‐1, may be useful in some cases. GATA‐3 immunostaining for metastatic breast carcinoma was helpful in our case and has not been previously reported in a thyroid metastasis sampled by FNA. Diagn. Cytopathol. 2016;44:530–534. © 2016 Wiley Periodicals, Inc.     

Pituitary Tumor-Transforming Gene 1 Is Expressed in Primary Ductal Breast Carcinoma,Lymph Node Infiltration,and Distant Metastases

Despite the advances that have been made in the fields of molecular and cell biology, there is still considerable debate explaining how the breast cancer cells progress through carcinogenesis and acquire their metastatic ability. The lack of preventive methods and effective therapies underlines the pressing need to identify new biomarkers that can aid early diagnosis and may be targets for effective therapeutic strategies. In this study we explore the pituitary tumor-transforming gene 1 (PTTG1) expression in primary ductal breast carcinoma, lymph node infiltration, and distant metastases. Three human cell lines, 184B5 derived from normal mammary epithelium, HCC70 from a primary ductal carcinoma, and MDA-MB-361 from a breast metastasis, were used for quantifying PTTG1 mRNA expression. The PTTG1 immunohistochemical expression was carried out on specimens taken from eight patients with invasive ductal breast cancer who underwent surgical treatment and followup for five years retrospectively selected. The study demonstrated that PTTG1 is expressed gradually in primary ductal breast carcinoma, lymph node infiltration, and distant metastases. Our findings suggest that the immunohistochemical evaluation of PTTG1 expression might be a powerful biomarker of recognition and quantification of the breast cancer cells in routine pathological specimens and a potential target for developing an effective immunotherapeutic strategy for primary and metastatic breast cancer.     

乳腺导管原位癌外科手术治疗的研究进展

乳腺导管原位癌是一种多发恶性肿瘤,其本质为癌细胞累及上皮全层,且仅局限在导管内尚未突破基底膜的肿瘤。近年来,随着医学技术的快速发展,乳腺导管原位癌检出率明显提升,且治疗措施也相应改进。外科手术是临床上常用的治疗乳腺导管原位癌的方法,且涉及手术类型较多,效果不一。文章对临床上外科手术治疗乳腺导管原位癌的研究进行综述,以期为临床实践和研究提供必要的参考依据。     

A metastatic renal carcinoid tumor presenting as breast mass: a diagnostic dilemma

We present clinicopathological and cytological findings of a well-defined breast mass in a patient with history of primary renal carcinoid tumor. Fine-needle aspiration (FNA) cytology showed monotonous tumor cells with plasmacytoid appearance arranged singly and in small clusters. Occasional tumor cells were arranged in acinar architecture resembling glandular differentiation. Tumor cells showed fine speckled chromatin. The unusual location for metastasis of this rare type of carcinoid tumor and overlapping cytological features with primary mammary carcinoma led to an erroneous preliminary cytological diagnosis of primary breast carcinoma with plasmacytoid features. Tumor cells in the corresponding cell block showed strong diffuse positivity for synapthophysin and pan-cytokeratin with weak focal positivity for chromogranin markers. These patterns of immunostaining were similar to the original renal carcinoid tumor. To the best of our knowledge, a few cases of carcinoid tumor metastatic to the breast have been reported in the literature and more than half of these cases were initially misdiagnosed as primary breast carcinoma causing unnecessary surgical treatment. This is a first reported case of metastatic renal carcinoid tumor into breast diagnosed with FNA biopsy. This report highlights the cytological features of well-differentiated neuroendocrine tumor (carcinoid tumor) and its potential diagnostic pitfalls.     

Ductal carcinoma-in-situ of the breast: Fine-needle aspiration cytology of 12 cases

Aspiration specimens from 12 patients with histologically documented ductal carcinoma-in-situ (DCIS) of the breast (seven patients) or DCIS with minute foci of stromal invasion (five) were evaluated. Five patients presented with palpable masses, 1.5–4.0 cm, and four patients presented with localized thickening, associated with nipple erosion and discharge in two of them. One patient had nipple inversion, and one patient had bilateral nipple discharge. In one patient, no apparent abnormality of the breast was present. Mammography was either suspicious for or strongly suggestive of carcinoma in 10 patients and negative in two. Aspirates from all patients were composed of fragments of atypical ductal epithelium and numerous single epithelial cells. In nine cases, the smears were hypercellular and similar to aspirates of typical invasive ductal carcinoma. Calcifications were present in six cases. In four of these, associated tumor necrosis was evident. Cytologic features separating DCIS patients from those showing minimal stromal invasion or common types of invasive ductal carcinoma (IDC) were not identified. We conclude that fine-needle aspiration cytology of DCIS is identical to that of IDC. If preoperative radiotherapy or chemotherapy is considered in the management of invasive breast carcinoma, cutting-needle biopsy for confirmation of tumor invasion is necessary.     

Breast metastasis from a colonic adenocarcinoma: a case report and literature review

Metastasis to the breast from extramammary tumors are uncommon and metastatic colon carcinoma (MCC) to the breast is extremely rare. A case history is presented of a 42 year-old woman with a finding of a breast lump. One year before,she had undergone an anterior colon resection for a rectal carcinoma. Mammographic examination revealed a high density, well demarcated, 3 cm lesion located in the upper outer quadrant of left breast, along with smaller multiple bilateral nodules. Following breast biopsy, the final diagnosis of MCC was based on the absence of any precursor lesion within the breast (no surrounding ductal carcinoma in situ) and of the expression of cytokeratin 20 and β-catenin on immunohistochemistry.The treatment strategy for metastatic breast disease is based on a proper assessment of such cases by surgeons,radiologists and pathologists.     

肺类癌型微小瘤的临床病理及其形态发生分析

目的 描述肺类癌型微小瘤的病理特征和免疫表型,探讨其发生的形态学基础。方法 对3例支气管扩张症(支扩)伴发微小瘤进行临床病理学观察,另11例支扩和2例正常肺作对照;应用免疫组织化学En Vision法检测其特异性标志物和标记气道上皮内神经内分泌细胞(NECs)。结果肺类癌型微小瘤多为散发多灶性镜下结节,呈簇状、巢状或索团状,分布于支扩受损的支气管壁旁、细小支气管周围和瘢痕化的组织中;由短梭形或小圆形细胞构成,核呈圆形、椭圆或长椭圆形,染色深;胞质弱嗜酸性;细胞嗜银性强;强表达神经元特异性烯醇化酶(NSE)、嗜铬素、降钙素、胃泌素等神经内分泌性标志物,小灶性表达绒毛膜促性腺激素(HCG)、促肾上腺皮质激素(ACTH)、5-羟色胺(5-HT),弱表达细胞角蛋白(CK)、上皮膜抗原(EMA)、S-100。微小瘤旁气道黏膜上皮NECs明显增生,比不伴微小瘤的支扩肺和正常肺气道黏膜上皮内NECs计数的差异均具有统计学意义(P值均＜0．001)。结论肺微小瘤具有周围型典型性类癌的病理特征和免疫表型,可能是典型性类癌发生的早期阶段。它的发生可能与肺慢性损伤导致慢性缺氧刺激NECs增生有关。     

Fine-needle aspiration of metastatic renal-cell carcinoma masquerading as primary breast carcinoma

This report details a fine-needle aspiration biopsy performed in the investigation of two right breast nodules in a patient with previous history of lumpectomy for infiltrating ductal carcinoma in the same breast 3 years before. Because the cytology was atypical for a mammary carcinoma and cells did not match the morphology of the previous breast carcinoma, a tissue biopsy was recommended, revealing the presence of metastasis from a previously silent primary renal-cell carcinoma. This report illustrates not only how metastatic lesions in the breast can masquerade clinically as a primary carcinoma but also the necessity for the cautious approach to interpreting the fine-needle aspiration biopsy of these lesions. Furthermore, essential guidelines necessary to distinguish primary from metastatic lesions in the breast are presented. Diagn. Cytopathol. 1998;18:343–345. © 1998 Wiley-Liss, Inc.     

Papillary carcinoma of the breast in a male patient with a treated prostatic carcinoma diagnosed by fine-needle aspiration biopsy: a case report and review of the literature

Papillary carcinoma of the male breast is very rare. In this case report, we describe the cytologic, histologic, immunohistochemical, and radiological findings of a papillary carcinoma of male breast. A 67-yr-old man, who had a previous history of prostatic adenocarcinoma, presented with a retroareolar painless mass. There was no known history of breast cancer in his family. A fine-needle aspiration biopsy (FNAB) was performed. Cytological examination revealed a cellular aspirate with three-dimensional papillary clusters. A diagnosis of papillary lesion favoring papillary carcinoma was rendered. Immunohistochemical staining of the cell-block of the FNAB revealed the presence of mammaglobin, and the absence of prostatic specific antigen. The patient underwent lumpectomy, which showed a moderately differentiated infiltrating papillary carcinoma with adjacent areas of ductal carcinoma in situ. FNAB is a useful technique in identifying male breast carcinoma. In conjunction with ancillary studies, this procedure can effectively differentiate between a primary versus metastatic lesion.     

On the origin of the so-called tumorlets of the lung

A light and electron microscopic study of multiple tumorlets in a 66 year old female is presented. Clinically the patient had had chronic obstructive lung disease with bronchiectasis of the right upper lobe. Aside from severe bronchiectatic alterations, the resected lobe showed typical tumorlets. On electron microscopic study, these were shown to consist of cells containing large numbers of a neurosecretory type of granule, which was identical to those present in the bronchial counterpart of the intestinal argentaffin (Kulchitsky) cell, as well as in pulmonary carcinoid and oat cell carcinoma cells. Our studies suggest the possibility of a histogenetic relationship between tumorlets, bronchial carcinoid tumors, and oat cell carcinoma, the cell of origin in each case being the bronchial counterpart of the intestinal argentaffin cell.     

Thyroid metastasis of clear cell renal carcinoma: Report of a case

Renal cell carcinoma can recur many years after diagnosis and nephrectomy metastasizing even in uncommon sites, including thyroid gland. Thyroid metastases are extremely rare, the most frequent site of origin are renal tumors. Metastases in thyroid gland appear as painless nodules or masses, “cold” at scintiscan. We report the case of a 67‐year‐old male patient affected by clear cell renal carcinoma, diagnosed by fine‐needle aspiration cytology procedures, and treated with anticancer medical therapy, who noticed after some months a mass in the neck‐thyroid region requiring deeper medical investigations. By this way, thyroid fine‐needle aspiration cytology reported a lesion made of malignant epithelial cells compatible with metastases of renal carcinoma (clear cell). Clinical and pathological data, together with immunostaining, supported the diagnosis of metastatic clear cell renal carcinoma. The diagnosis of metastatic disease, although difficult clinically and pathologically, should be suspected in patients with a clinical history of cancer, particularly in case of renal cell carcinoma, but fine‐needle aspiration cytology can provide the clue for diagnosis. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Fine-needle aspiration cytology of metastatic neoplasms in the breast

Twenty cases of metastatic neoplasms in the breast were identified in a series of 1,034 fine-needle aspirations (FNAs) of the breast, of which 389 were malignant. Patients with breast carcinomas in whom metastasis to the contralateral breast developed were excluded from this study. This series consisted of 17 women and 3 men, ranging in age from 28 to 63 years (mean, 49 years). The tumors included oat cell carcinoma (three), melanoma (three), ovarian serous carcinoma (one), bronchogenic adenocarcinoma and squamous carcinoma (four and two, respectively), lymphoma (two), carcinoid (two), transitional cell carcinoma (one), plasma cell myeloma (one), and rhabdomyosarcoma (one). In two patients, the breast mass was the first manifestation of an extramammary cancer (two adenocarcinoma of the lung). Eleven patients died of disseminated cancer shortly after the breast metastasis was diagnosed. In most cases, the aspirates displayed the cytologic features characteristic of the primary tumors, thereby establishing the metastatic nature of the neoplasm. In four cases (two carcinoids, one myeloma, and one rhabdomyosarcoma), the cytologic features were difficult to differentiate from a primary breast carcinoma; however, the final diagnosis was established by electron microscopic examination and immunocytochemical studies on the aspirates. One case (adenocarcinoma of the lung) was misdiagnosed as primary breast carcinoma on both FNA and mastectomy specimen. Because metastatic neoplasms in the breast may mimic primary breast tumors, the authors recommend the following: (1) Evaluation of FNA of breast should be done with complete knowledge of the patient's clinical history. (2) The possibility of metastasis should be suspected in lesions with unusual cytologic patterns. (3) Ancillary studies on FNA can be helpful in interpreting selected cases.     

Metaplastic carcinoma of the breast with dominant squamous and sebaceous differentiation in the primary tumor and osteochondroid metaplasia in a distant metastasis: report of a case with review of sebaceous differentiation in breast tumors

Metaplastic breast carcinoma is an uncommon tumor that develops from conventional ductal mammary carcinoma, usually consisting of squamous and/or spindle cell components and/or mesenchymal elements. Although several morphological subtypes of metaplastic breast carcinoma are known, sebaceous metaplasia has not yet been described in this context. The authors report a case of an 84-year-old woman with a huge, ulcerated primary tumor in her left breast that had already been present for 10 years. Pulmonary and bone metastases and a tumor nodule in the contralateral breast were also detected at the time of admission. Left simple mastectomy was performed. Histological examination of the tumor revealed metaplastic carcinoma consisting of ductal carcinoma, which immunohistochemically exhibited a triple-negative immunoprofile, along with dominant areas of squamous and sebaceous differentiation. Adjuvant chemotherapy was subsequently given with partial regression of the systemic metastases. Seven months after surgery and diagnosis, a new, rapidly growing, large soft tissue metastatic tumor appeared in the intramuscular compartment of the patient's right thigh, which was removed and histologically examined. Morphologically this metastatic tumor showed ductal adenocarcinoma along with areas of sebaceous differentiation and, in addition, osteochondroid metaplasia. Immunohistochemically, unlike the primary, this tumor expressed HER-2. The case is presented because of its rarity, and sebaceous differentiation is also proposed as a novel type of metaplasia in this context, expanding the spectrum of the histological patterns of metaplastic breast carcinoma. The literature concerning breast sebaceous lesions is reviewed, and the hypothetical biological mechanisms responsible for the tumor pathogenesis in this case are discussed.     

Metastatic breast carcinoma identified in a uterine leiomyosarcoma

A rare example is described of an advanced invasive ductal carcinoma of the breast with concomitant metastatic foci in a uterine leiomyosarcoma. Both tumors arose in a 48-year-old woman, without any evidence of distant metastases as assessed on imaging at the time of diagnosis. The double diagnosis in this particular case was established on a combination of microscopic appearance of the uterine tumors in the hysterectomy specimen, immunophenotype assessment, and clinical information on the breast carcinoma. But the association between the two malignancies can be challenging and potentially difficult to prove.     

Immunohistochemical Markers for Distinguishing Metastatic Breast Carcinoma from Other Common Malignancies: Update and Revisit

Due to the high prevalence of breast cancer in the female, a metastasis from primary breast cancer is usually considered in the differential diagnosis of metastatic carcinoma in the female patient, even for those without a history of breast cancer, as some breast cancers are first diagnosed as metastases. Immunohistochemical analysis for breast cancer markers is the most common way to determine breast cancer origin besides clinical history and histology. In this review, we (1) summarize the commonly used and the newly identified breast cancer markers, including GCDFP-15, mammaglobin, GATA3, SOX10, and TRPS1; (2) point out the strengths and weaknesses of using these markers for breast cancers with luminal/epithelial or basal/myoepithelial differentiation; and (3) recommend diagnostic panels to differentiate breast carcinoma from carcinoma with similar morphology of other origins.     

What can we learn from the errors in the frozen section diagnosis of pulmonary carcinoid tumors? An evidence-based approach

The intraoperative diagnosis of pulmonary neuroendocrine tumors can be difficult. Frozen section diagnosis was requested on 87 neuroendocrine tumors including 58 typical carcinoids, 8 atypical carcinoids, 18 large cell neuroendocrine carcinomas, and 3 small cell carcinomas from 2405 patients that underwent frozen section diagnosis at Cedars-Sinai Medical Center from 2002 to 2007. The deferral and error rate for carcinoid tumors was 4.13% and 7.5%, respectively, and resulted in 4 unnecessary lobectomies and 2 second thoracotomies. The most common errors included misdiagnoses as lymphoma, squamous carcinoma or metastasis from breast carcinoma. Thirty one pathologic features were evaluated in the 66 carcinoid tumors and 10 frozen sections each of lymphoma, squamous cell carcinoma, and metastatic breast carcinoma. Seven pathologic features were significant by chi square test at P > .05. Positive likelihood ratios identified 11 pathologic features that were useful for the diagnosis of carcinoid tumor from other neoplasms. The applicability of the 11 pathologic features was tested with a group of pathologists, resulting in significant improvement in diagnostic accuracy as measured by pre and posttests. The value of evidence-based pathology and Bayesian statistics to evaluate complex differential diagnoses in pathology is discussed.