Metaplastic carcinoma of the breast: p53 analysis identified the same point mutation in the three histologic components.

A rare case of metaplastic carcinoma of the breast with both squamous metaplasia and cartilaginous metaplasia was reported. Histologically, the neoplasm revealed complex features, which were consisting of invasive ductal carcinoma, squamous carcinomatous component and chondrosarcomatoid component. Gradual transition of each component was recognized microscopically. p53 mutation analysis disclosed the same point mutation in three histologically different components, but not in the normal epithelium. Based on the morphologic findings, immunohistochemical findings and the p53 mutation analysis, we concluded that these three components in the tumor originated from the same duct progenitor cells.     

Primary mucin-producing adenosquamous carcinoma of the thyroid gland

A rare case of mucin-producing adenosquamous carcinoma of the thyroid gland is reported in a 57-year-old woman. Light microscopically, much of the tumor showed a feature of mucin-producing adenosquamous carcinoma; squamous cells and mucous signet ring cells. In the lower portion of the tumor, a calcified area containing small foci of follicular carcinoma and its squamous cell metaplasia was accompanied. Histochemically, neutral, non-sulphated and sulphated acid mucins were found in the mucous cells, and no thyroglobulin or calcitonin was detected in the tumor cells. Electron microscopically, some tonofibrils and mucin production were observed concomitantly in the tumor cells. These findings suggested the possibility that this mucin-producing adenosquamous carcinoma originated from squamous cell metaplasia of pre-existing follicular carcinoma.     

Metaplastic carcinoma of the breast arising within complex sclerosing lesion: a report of five cases

AIMS: This study presents a series of five cases in which metaplastic carcinoma, predominantly low-grade adenosquamous carcinoma, of the breast is seen arising within a background of a complex sclerosing lesion. This association has been recognized previously but has not been documented in detail. This study describes the characteristics of the components present in each case and discusses the existing literature. This observation adds further evidence to support an association between some types of invasive breast carcinoma and sclerosing lesions of the breast. METHODS AND RESULTS: Four of these cases were received as referral cases for opinion. The fifth was received as part of the routine surgical workload within our own institution. Two patients presented following mammographic screening and three symptomatically; their mean age was 62 years (range 49-68). The mean lesion size was 16 mm (range 7-24). All five lesions showed features of a complex sclerosing lesion/radial scar in the form of central sclerosis with elastosis and radiating benign entrapped tubules. One had associated benign papillary structures and two had focal benign squamous metaplasia. Four cases showed coexisting but distinct areas of low-grade adenosquamous carcinoma with glandular and squamous epithelial differentiation in a spindle cell background. One case had associated undifferentiated spindle cell carcinoma. Detailed immunophenotypic characteristics of two cases are presented. CONCLUSIONS: This series illustrates a postulated but previously unconfirmed association between an unusual form of metaplastic breast carcinoma (adenosquamous carcinoma) and complex sclerosing lesions. The mechanisms of induction of breast carcinoma are poorly understood but these observations further emphasize the potential for sclerosing lesion of the breast to be associated with, and possibly give rise to, invasive carcinoma of different types. The precise nature of the interaction between the pathological processes remains unclear.     

Pleomorphic carcinoma with osteoclastic giant cells of the breast: Immunohistochemical differentiation between coexisting neoplastic and reactive giant cells

Herein is described a unique case of breast carcinoma with two different types of giant cells noted in both cytological and histological specimens. A 51-year-old Japanese woman noticed a hard mass in the upper outer quadrant of her left breast. Aspiration cytology exhibited numerous anaplastic giant cells; the cytological diagnosis was high-grade ductal carcinoma, although a few osteoclastic giant cells were also observed. A left simple mastectomy and sentinel lymph node biopsy were performed. Histologically, approximately 90% of the tumor was composed of giant cells; conventional invasive ductal carcinoma and ductal carcinoma in situ were found focally at the periphery of the tumor. The main part of the tumor contained both anaplastic, neoplastic giant cells and non-neoplastic, osteoclastic giant cells that were distinguishable from nuclear atypism. The presence of the two types of giant cells was also confirmed on immunohistochemistry using a histiocytic marker (CD68) and two epithelial markers (AE1/AE3 and CAM5.2). Based on the latest World Health Organization classification, the diagnosis was pleomorphic carcinoma with osteoclastic giant cells. To the authors' knowledge there has been no previous report on this subject except for a single case mentioned in Rosen's Breast Pathology .     

Histogenesis of metaplastic breast carcinoma and axillary nodal metastases

A 40-year-old breast-feeding woman presented with left breast swelling. On physical examination a 7 cm mass was found in the breast. Because biopsy demonstrated malignant tissue, mastectomy with axillary nodal dissection was performed. Pathological findings were consistent with metaplastic breast carcinoma with nodal metastases. The primary tumor consisted of three types of invasion: ductal, squamous, and sarcomatous. Furthermore, three morphological transitions were observed: ductal–squamous, ductal–sarcomatous, and squamous–sarcomatous. Ductal–squamous (12/18 microscopy slides) and squamous–sarcomatous transitions (10/18) were more commonly observed than ductal–sarcomatous transition (3/18). Furthermore, immunohistochemistry showed loss of epithelial marker (cytokeratin) and acquisition of mesenchymal markers (vimentin and α-smooth muscle actin) in the sarcomatous component. These findings suggested that epithelial–mesenchymal transition had occurred in the tumor and that two pathways, ductal–squamous–sarcomatous and ductal–sarcomatous transition, were involved in progression of metaplastic breast carcinoma. The main pathway appeared to be ductal–squamous–sarcomatous transition. Regarding the nodal metastases, of 13 positive nodes, ductal, squamous, and sarcomatous components were observed in 13, seven, and two nodes, respectively. Moreover, as in the primary tumor, ductal–squamous and squamous–sarcomatous transitions were observed. This suggested that the ductal component metastasized to the nodes and that epithelial–mesenchymal transition subsequently occurred within the nodes.     

PRIMARY MUCIN-PRODUCING ADENOSQUAMOUS CARCINOMA OF THE THYROID GLAND

A rare case of mucin-producing adenosquamous carcinoma of the thyroid gland is reported in a 57-year-old woman. Light microscopically, much of the tumor showed a feature of mucin-producing adenosquamous carcinoma; squamous cells and mucous signet ring cells. In the lower portion of the tumor, a calcified area containing small foci of follicular carcinoma and its squamous cell metaplasia was accompanied. Histochemically, neutral, non-sulphated and sulphated acid mucins were found in the mucous cells, and no thyroglobulin or calcitonin was detected in the tumor cells. Electron microscopically, some tonofibrils and mucin production were observed concomitantly in the tumor cells. These findings suggested the possibility that this mucin-producing adenosquamous carcinoma originated from squamous cell metaplasia of pre-existing follicular carcinoma. ACTA PATHOL. JPN. 37: 1157 -1164, 1987.     

Cytological study of 20 cases of solid-papillary carcinoma of the breast

Solid-papillary carcinoma (SPC) of the breast is a rare variant of low-grade intraductal carcinoma but there are few cytological studies. We examined 20 cases of SPC of the breast, aged 31-80 (mean age 66.0 yr), to define the cytological features. In each of the cytological specimens, we could find both malignant and benign cytological features; the former were characterized by hypercellularity, highly discohesive clusters, numerous isolated cells, and severe overcrowding cells, while the latter were marked by small and bland nuclei, a low nuclear-cytoplasmic ratio, and inconspicuous nucleoli. Neither abnormal naked nuclei of tumor cell origin nor oval naked nuclei of myoepithelial cell origin were seen.We also reviewed the cytological findings of SPC as well as neuroendocrine carcinomas with intraductal components that had been reported and we concluded that the coexistence of malignant and benign features was the most characteristic cytological feature of SPC.     

Combined signet ring cell and glassy cell carcinoma of the uterine cervix arising in a young Japanese woman: a case report with immunohistochemical and histochemical analyses

Signet ring cell carcinoma and glassy cell carcinoma are both rare histological subtypes of uterine cervical cancer. This report is of a case of uterine cervical carcinoma arising in a 29-year-old woman who had major components of signet ring cell carcinoma and glassy cell carcinoma within the same tumor. Histochemical and immunohistochemical analyses, including high and low molecular weight cytokeratins, p63 and MUC5AC, additionally demonstrated the squamous and adenocarcinomatous differentiation in the neoplastic cells, which showed otherwise unclassifiable morphology on the haematoxylin-eosin sections. A wide range of differentiation described above supports the speculation that glassy cell carcinoma may arise from the multipotential immature cells that can differentiate into both squamous and glandular cells. It would be precise to classify this tumor as adenosquamous carcinoma. Although adenosquamous carcinoma is not a rare histological subtype in the uterine cervix, it should be necessary to report the presence of glassy cells and signet ring cells when present because the presence of both components is associated with an unfavorable clinical behavior.     

Invasive ductal carcinoma of the breast with signet-ring cell and mucinous carcinoma components: diagnostic utility of immunocytochemistry of signet-ring cells in aspiration cytology materials

Breast cancer with signet-ring cells is very rare. In this article, we present a case of invasive ductal carcinoma with signet-ring cells and mucinous carcinoma components, which could be diagnosed as a primary cancer by immunocytochemical study of fine-needle aspiration cytology material. A 73-yr-old Japanese woman noticed a palpable mass in the left breast. The aspiration cytology disclosed the monotonous proliferation of signet-ring cell with cytological atypia. The immunocytochemical examination of neoplastic cells showed a positive reaction for estrogen receptor. The extensive examination of body before the operation did not disclose any tumors in other anatomic sites. The histological examination of surgically resected breast tumor showed invasive ductal carcinoma with foci of signet-ring cell and mucinous carcinomas. Finally, our preliminary report suggests that immunocytochemical examination of aspiration cytology materials may provide useful information in searching the primary site of breast carcinoma with signet-ring cells.     

Solid papillary carcinoma of the breast: imprint cytological and histological findings

Solid papillary carcinoma is a rare breast lesion, but this entity remains poorly recognized. In this article, we report a case of solid papillary carcinoma of the breast with focus on cytological and histological findings. A 66-year-old Japanese woman presented with nipple discharge. Imprint cytology obtained from the surgically resected breast specimens showed a plasmacytoid appearance and spindle cell morphology with low-grade atypia. Histologically, the tumor revealed findings of solid papillary carcinoma and predominantly showed an intraductal lesion with focal minimal invasion into the breast parenchyma. Fibrovascular cores with hyalinization were seen. Proliferation of short spindle cells was also focally observed. Pseudorosette formation or nuclear palisading at the stromal-glandular interface was seen, and intracellular or extracellular mucin deposition was occasionally identified. Nuclear atypia generally showed low grade. Finally, clinicians, cytotechnologists, and pathologists should recognize this rare tumor entity because this tumor is a malignant neoplasm showing characteristic pathological findings.     

Fine-needle aspiration biopsy of low-grade cribriform cystadenocarcinoma of the salivary gland

Low-grade cribriform cystadenocarcinoma (LGCCC) is a rare tumor, defined in the 2005 WHO classification as a primary salivary duct tumor. Previously, the neoplasm had been recognized as a variant of salivary duct carcinomas. A 56-year-old Japanese woman noticed a mass in the left subaural region. On radiological examinations, a multicystic tumor was seen in the left parotid gland. Fine-needle aspiration biopsy was performed. The smears revealed several characteristic cytologic features. The tumor cells were arranged in irregular overlapping and showed inconspicuous nuclear atypia with variable-sized and irregularly shaped cytoplasmic vacuoles. Based on these findings, a cystic tumor with uncertain malignancy was diagnosed. A parotidectomy was performed, because the tumor was slowly growing and contained solid components on the radiological images. Based on the histologic findings, along with immunohistochemistry, LGCCC was diagnosed based on resemblance to breast low-grade ductal carcinoma in situ and intraductal proliferation of tumor cells. This is the first report of the cytomorphological findings of LGCCC.     

Fine-needle aspiration of a metaplastic breast carcinoma with extensive melanocytic differentiation: a case report

Metaplastic carcinomas of the breast are uncommon breast tumors with aberrant cellular differentiation, most commonly showing ductal, squamous, and mesenchymal components. A breast carcinoma composed of both epithelial and melanocytic differentiation is rare, with only four previously reported cases in the literature. We present the fifth reported case, where the diagnosis was suggested by fine-needle aspiration (FNA) and later confirmed after the surgical specimen was excised. Histologically, this neoplasm revealed multidirectional differentiation, consisting primarily of squamous and melanocytic cell types, with focal glandular and osseous metaplasia. Based on the morphologic, immunohistochemical, and ultrastructural findings, we conclude that such tumors fall within the spectrum of metaplastic carcinomas of the breast. We believe that this case will further contribute to the understanding of this enigmatic tumor.     

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.     

Fine-needle aspiration of low grade adenosquamous carcinoma of the breast

Low-grade adenosquamous carcinoma is an unusual variant of mammary carcinoma. This malignancy generally presents as a palpable mass without mammographic microcalcifications, and fine-needle aspiration may be the initial technique selected for diagnosis. To our knowledge, the cytologic findings associated with this neoplasm have not been reported. We report a case of low-grade adenosquamous carcinoma of the breast in a 57-yr-old woman, initially studied by fine-needle aspiration cytology and confirmed by excisional biopsy. The aspiration biopsy smears were characterized by low cellularity and small disoriented clusters containing uniform cells of small to medium size. Bipolar cells were not seen in the background. The diagnostic features and differential diagnosis of this unusual neoplasm are reviewed. Diagn Cytopathol 1996;14:321–324. © 1996 Wiley-Liss, Inc.     

Double cancer consisting of adenosquamous and hepatocellular carcinomas of the liver

A very rare case of a double cancer consisting of adenosquamous and hepatocellular carcinomas of the liver in a 65-year-old-man is discussed. The patient was hospitalized with epigastralgia in May 1997. Abdominal computed axial tomography revealed a tumor located in the left lobe of the liver and a left hepatic lobectomy was performed. The tumor recurred several months after surgery and the patient died on 4 June 1999. At autopsy, both a major tumor mass with extensive involvement, located in the surgical margin, and a small mass located in S7 were discovered. Microscopically, the major tumor was diagnosed as adenosquamous carcinoma and the small one in S7 as hepatocellular carcinoma. To our knowledge, this is the first case of a double cancer consisting of adenosquamous and hepatocellular carcinomas of the liver. The pathological findings support the hypothesis that this tumor developed as a squamous transformation of adenocarcinoma.     

Breast carcinoma with predominant neuroendocrine differentiation

Neuroendocrine differentiation can be identified in a subset of human breast carcinomas, either as scattered cells or as a predominant neuroendocrine component. We report a case of an invasive breast carcinoma largely composed of neuroendocrine cells. Eight years after a left mammary lumpectomy for a pT2N1MO SBR III invasive ductal carcinoma, a 67-years-old woman presented with a metastastic neuroendocrine sternal mass. To establish a relationship between mammary carcinoma and bone metastasis, histological slides of both the breast tumor and axillary lymph nodes were reviewed, and an immunohistochemical study was performed. They showed that: a) the mammary carcinoma was composed of a majority of small and large neuroendocrine cells synaptophysin +, NCAM+, chromogranin - (80%), associated with 2 other differentiated non endocrine components, one of metaplastic squamous carcinoma (10%) and the other of ductal carcinoma (10%); b) 4 axillary lymph nodes were involved by the ductal component which contained few NCAM + but synaptophysin - cells; c) Estrogen and progesterone receptors and HER2 were negative in the breast tumor and the metastatic nodes. We discuss the histogenesis of composite mammary carcinomas with neuroendocrine differentiation, the outcome of each component and the prognostic relevance of such a diagnosis.     

Association of trisomy 8 and squamous differentiation in an endometrial adenocarcinoma

Cytogenetic analysis was performed on a case of endometrial adenocarcinoma in which 10% to 15% of the tumor showed squamous differentiation. Of 26 cells examined, all had trisomy 1q and monosomy 16; four cells (15%) also showed trisomy 8. Trisomy 8 is an unusual finding in endometrial carcinoma, having been reported in only one other case, which was an adenosquamous carcinoma. Our findings suggest that trisomy 8 may be a marker of squamous differentiation in endometrial carcinoma.     

Fine-needle aspiration biopsy of metaplastic carcinoma of the breast: Report of a case with abundant myxoid ground substance

Metaplastic carcinoma (MC) is an uncommon neoplasm of the breast. There are several variants of MC depending on the dominant histologic pattern. The components include overt infiltrating ductal carcinoma, extensive squamous differentiation and spindle cell proliferation with or without chondroid or osseous heterologous elements. In FNA smears, only 57% of cases show both ductal carcinoma and metaplastic component. Thus, in almost one half of the cases, the diagnosis is not possible by FNA. Often it is difficult to define the epithelial or sarcomatous character of malignant cells. We describe a case of metaplastic carcinoma of the breast studied by fine-needle aspiration cytology in which myxoid ground substance was the dominant feature in the cytology smears. The rest of the material was composed of scanty isolated atypical cells with large and irregular nuclei. It is important to bear in mind the diagnosis of MC and make a careful search for atypical cells when the cytological smears are mainly composed of myxoid ground substance. Diagn Cytopathol 1996;14:325–327. © 1996 Wiley-Liss, Inc.     

Cytopathological features of an epithelial-myoepithelial carcinoma with predominant clear myoepithelial cells in the parotid gland

Epithelial-myoepithelial carcinoma (EMC) is a rare low-grade carcinoma occurring most frequently in the parotid gland. Most EMCs consist of two cell types that typically form double-layered ductal structures. However, occasionally EMC presents predominantly clear myoepithelial cells. A 34-year-old man visited in August 1993 and was diagnosed as having clear-cell carcinoma. The tumor was curatively resected. However, in the following 5 years, recurrence developed a total of five times. The imprint cytological feature of the recurrence at the third time showed monophasic clear cells in sheet clusters with overlapping. Most of the clear tumor cells presented an expression to alpha-smooth muscle actin (SMA). The imprint cytological feature of the recurrence at the fifth time showed increase of nuclear atypia with coarse chromatin patterns and large nucleoli. In addition to cytological findings, the cytological diagnosis of EMC with predominant clear myoepithelial cells requires a definite expression to SMA.     

Adenosquamous carcinoma of the pancreas with an acantholytic pattern together with osteoclast-like and pleomorphic giant cells

A 45 year old man presented with abdominal pain, loss of appetite, and significant weight loss over a period of about four weeks. Imaging of the abdomen showed a mass in the region of the head of the pancreas. In view of the size of the mass and the clinical picture, a Whipple's procedure was performed. Histological evaluation of the pancreatic tumour showed an adenosquamous carcinoma (predominantly composed of squamous carcinoma), which was extensively infiltrative with perineural invasion and involvement of peripancreatic lymph nodes. Areas of pancreatic intraepithelial neoplasia grade III and merging of the squamous and adenocarcinoma components were evident. Unusual histological features that characterised this case included a pronounced acantholytic pattern within the squamous carcinoma component, and the presence of both osteoclastic and pleomorphic giant cells. Giant cells have not been documented previously in association with an adenosquamous carcinoma. Although an acantholytic pattern has been noted in squamous carcinomas in other sites, this is the first report of such a pattern in an adenosquamous carcinoma of the pancreas.