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1.  Seborrheic inclusion cyst of the skin positive for cytoplasmic inclusion bodies and HPV antigen 
Seborrheic inclusion cyst (SIC) is a very rare variant of epidermal cyst of the skin. SIC shows seborrheic keratosis (SK)-like lesion in epidermal cyst. SIC is extremely rare; only 6 case reports have been published in the English literature. However, no immunohistochemical study of SIC has been reported. A 41-year-old Japanese man noticed a subcutaneous tumor in the neck. Physical examination showed slightly mobile tumor in the subcutaneous tissue, and total excision was performed. Grossly, the tumor (1 x 1 x 0.8 cm) was cyst containing atheromatous keratin. Microscopically, the lesion is a cyst containing keratins. About one half of the cyst showed features of epidermal cyst consisting of mature squamous epithelium with granular layers. The other one half showed SK-like epidermal proliferation. The SK-like area showed basaloid cell proliferation with pseudohorn cysts. No significant atypia was noted. Many eosinophilic cytoplasmic inclusion bodies were noted in the SK-like area. Immunohistochemically, the SK-like area was positive for pancytokeratin AE1/3, pancytokeratin CAM5.2, p63, and Ki-67 (labeling=8%) and HPV, but negative for p53. The pathological diagnosis was SIC.
PMCID: PMC3396058  PMID: 22808299
Seborrheic inclusion cyst; epidermal cyst; cutaneous pathology; immunohistochemistry; HPV
2.  A pre-pubertal girl with giant juvenile fibroadenoma: A rare case report 
Highlights
•Virginal hypertrophy, giant fibroadenoma, and cystosarcoma phyllodes are the important differential diagnoses to be considered when one encounters a large breast mass in a young female patient.•Fibroadenoma 5 cm or more in diameter is considered as giant fibroadenoma. Giant fibroadenoma is the most common cause of breast enlargement and cause asymmetry of breast in adolescent and young adult female.•Ultrasonography is imaging modality of choice and cytological examination should be done to arrive at a diagnosis. Giant fibroadenoma should always be treated with breast conserving surgery.
Introduction
Fibroadenomas are benign neoplasms usually arising between the ages of 15–25 years. Approximately 0.4% fibroadenomas arise in juvenile age group. Usually the diagnosis is straightforward by clinical examination and FNAC. But sometimes rapid growth and giant size may pose difficulty in clinical approach.
Case presentation
In this paper we are presenting a rare case of giant juvenile fibroadenoma in a 10 years old girl which was diagnosed by FNAC and treated by excision. Diagnosis was confirmed by histopathology.
Discussion
Giant juvenile fibroadenomas are over 5 cm in diameter and tend to show rapid growth mimicking a carcinoma. But histological features are similar to smaller fibroadenomas and can be enucleated.
Conclusion
Through this case we want to emphasize that these giant benign neoplasms should be suspected in any pre-pubertal girl with breast lump and should always be treated with breast conserving surgery.
doi:10.1016/j.ijscr.2015.09.026
PMCID: PMC4643459  PMID: 26433926
Giant fibroadenoma; Pre-pubertal girl; Breast conservation surgery
3.  Fibroadenoma versus phyllodes tumor: distinguishing factors in patients diagnosed with fibroepithelial lesions after a core needle biopsy 
PURPOSE
We aimed to identify factors that might help differentiate phyllodes tumors from fibroadenomas among cases in which a fibroepithelial breast lesion was diagnosed from core needle biopsy (CNB) under imaging guidance.
MATERIALS AND METHODS
A retrospective review was performed on 213 lesions in 200 patients who had undergone both CNB and excisional biopsy during a four-year period between 2008 and 2011. The final pathology revealed 173 fibroadenomas and 40 phyllodes tumors. The data, including patient characteristics, clinical presentation, and mammography, ultrasonography (US), and pathology findings were analyzed.
RESULTS
Upon univariable analysis, the factors that significantly helped to identify phyllodes tumors consisted of the presenting symptoms (palpable mass or breast pain), increased size on clinical examination, hyperdense mass on mammogram, and the following three US features: heterogeneous echo, presence of round cysts within the mass, and presence of clefts within the mass. The pathologist’s suggestion of a phyllodes tumor was also helpful. The factors that remained statistically significant upon multivariable analysis consisted of symptoms of breast pain, the presence of clefts on US, the presence of round cysts on US and the pathologist’s favoring of phyllodes tumors from a CNB specimen.
CONCLUSION
A multidisciplinary approach was needed to distinguish phyllodes tumors from fibroadenomas in patients who had undergone CNB. US findings (clefts and round cysts), suggestive pathological diagnoses, and clinical symptoms were all useful for the decision to surgically remove the fibroepithelial lesions diagnosed from CNB.
doi:10.5152/dir.2013.13133
PMCID: PMC4463252  PMID: 24356293
4.  Congenital Giant Keratinous Cyst Mimicking Lipoma: Case Report and Review 
Epidermal cysts represent the most common cutaneous cysts. They arise following a localized inflammation of the hair follicle and occasionally after the implantation of the epithelium, following a trauma or surgery. Conventional epidermal cysts are about 5 cm in diameter; however, rare reports of cysts more than 5 cm are reported in the literature and are referred as “Giant epidermal cysts.” Epidermal cysts although common, can mimic other common benign lesions in the head and neck area. A thorough clinico-pathologic investigation is needed to diagnose these cutaneous lesions as they differ in their biologic behavior, treatment, and prognosis. We report a case of a giant epidermoid cyst in the scalp area of a young female patient which mimicked lipoma on clinical, as well as cyotological examination. We also present a brief review of epidermal cysts, their histopathological differential diagnosis, and their malignant transformation.
doi:10.4103/0019-5154.169160
PMCID: PMC4681229  PMID: 26677303
Giant epidermal cyst; histopathology; keratinous cyst; scalp
5.  A rare case of isolated hydatid cyst of breast 
Highlights
•Hydatid cyst of the breast is very rare.•It is challenging to differentiate it from other tumoral lesions of the breast as it might mimic fibroadenoma, phyllodes tumors, chronic abscesses or even carcinoma.•Only few reports of breast hydatid cyst are published and majority of the reported cases have been diagnosed postoperatively as it is not possible to reach definitive diagnosis with clinical examination and radiological investigations only.•In spite of being very uncommon, it should be included in differential diagnosis of breast lumps for patients living in endemic areas.•Surgical excision of the cyst is the treatment of choice.
Introduction
Hydatid cyst of the breast is very rare. It is challenging to differentiate it from other tumoral lesions of the breast. Only few reports of breast hydatid cyst are published and majority of the reported cases have been diagnosed postoperatively as it is not possible to reach definitive diagnosis with clinical examination and radiological investigations only.
Presentation of case
A 31-year old woman presented with a painless lump in the right breast since one year duration. On clinical examination, a non-mobile, firm lump was detected in the right breast associated with nipple retraction, but there was no axillary lymphadenopathy. This case was diagnosed as hydatid cyst incidentally during surgery from its gross appearance which mimics that of a liver hydatid cyst, normally common in this endemic area.
Discussion
Hydatid disease is a parasitic infection caused by the larval form of Echinococcus granulosus and seen endemically among sheep-raising communities. The breast can be a primary site or part of a disseminated hydatidosis. It might mimic fibroadenoma, phyllodes tumors, chronic abscesses, or even carcinoma. Preoperative diagnosis can be made by fine needle aspiration cytology. It also can be diagnosed by radiological or serologic means but neither of them is definitive. Surgery is the treatment of choice.
Conclusion
Hydatid cyst of the breast is very uncommon but it should be included in differential diagnosis of breast lumps for patients living in endemic areas.
doi:10.1016/j.ijscr.2014.10.093
PMCID: PMC4336384  PMID: 25582084
Hydatid cyst; Very rare; Painless Breast lump; Incidentally; Endemic
6.  Aggressive malignant phyllodes tumor 
Highlights
•Phyllodes tumor of breast could be either benign or malignant variety and they can grow into very large sizes and distort the breast.•WHO classifies tumors into benign, borderline and malignant and it is the best methods to predict the local recurrence, distant metastasis or bath after resection.•Borderline and malignant disease should have close follow up; as some of these tumors can rapidly change and metastasize.
Introduction
Originally described in 1838 by Muller, phyllodes tumor is a rare fibroepithelial neoplasm which represents roughly 0.3–0.9% of all breast cancers. Phyllodes tumor are divided into benign, borderline and malignant histologic categories. Malignant phyllodes tumor represent anywhere from 10–30% of all phyllodes tumors. This group has both the potential to recur locally and metastasize, however not all malignant phyllodes behave this way. The challenge lays in predicting which tumor will recur locally or metastasize. Distinguishing this subset of malignant phyllodes tumor is paramount.
Presentation of case
We present a case of malignant phyllodes which presented with metastatic disease. What is fascinating about this case is not only the initial presentation but also the aggressiveness of this variation of phyllodes tumor. The patient initially presented with a large mass which encompassed her whole right breast. On surgical pathology the mass measured roughly 31 cm in diameter and weighed over 10 kg. Within 5 weeks from surgery the patient had suffered brain metastases and also 6 local recurrent tumors. The patient passed roughly 11 weeks after her first visit to our office.
Conclusion
Despite biopsy proven malignant phyllodes tumor, it was near impossible to predict such a rapid course of disease progression in our patient. Our case illustrates the unpredictable nature of this disease in general and it possibly sheds light on a variant of the disease which had undergone an aggressive transformation.
doi:10.1016/j.ijscr.2014.12.041
PMCID: PMC4353966  PMID: 25697402
Phyllodes tumor; Malignant; Breast
7.  FATAL KERATOMAS DUE TO DEEP HOMOGRAFTS OF THE BENIGN PAPILLOMAS OF TARRED MOUSE SKIN  
Six out of eight epidermal papillomas, induced with tar in mice of homogeneous strain, have grown after transfer to the subcutaneous tissue of sucklings and weanlings. Five of them have been thus maintained for nearly or quite a year and a half, and in seven to nine successive groups of mice. The tumor studied longest has been kept going in five parallel lines since its primary implantation. The papillomas have all grown progressively in most instances, and proved fatal. None has altered except through the occurrence of derivative cancers, but these have arisen so often as only to be excluded on transfer by a rigorous selection of grafts. Histologically the papillomas have been of a single, completely unaggressive kind, yet transfer has disclosed great differences in their abilities. The tumors they form are of unique sorts. The cells of some are able-bodied (Type A), capable of spreading along bare connective tissue and keratinizing like normal, reparative epidermis. They line graft pockets, differentiate into the free space these provide, and form cysts densely packed with keratin. The papilloma is thus turned outside in. The cysts become huge as keratin accumulates in them, and eventually they rupture with result either in subcutaneous dissecting cysts or keratinizing surface growths that are often prodigious in size and fantastic in shape, but sometimes are completely like the cutaneous papillomas ordinarily induced by carcinogens, and tend, when small, to regress or come away as these frequently do. One growth of Type A was placed in the peritoneal cavity or in the liver, spleen or lung, and at all these situations it formed introverted cysts resembling the subcutaneous. The cells of other papillomas are more or less crippled (Type C). In extreme instances they are unable to spread laterally, and produce relatively little keratin. They fail to line graft pockets, but their keratin inflames the exposed connective tissue, extravasation ensues, and a continually enlarging, fluid-filled cyst forms, with walls that are bare except where a stalked or cauliflower papilloma exists, projecting inwards. At last the cyst ruptures and a second dissecting cyst forms, also devoid of papilloma tissue; or else the overlying skin undergoes pressure necrosis, the cyst fluid escapes through a rent, and fatal infection ensues. All gradations exist between Type A and Type C. The cancers derivative from both exhibit a marked disability,—though invasive they are almost or quite unable to extend along bare connective tissue. The papillomas that are possessed of this faculty spread beyond them along the cyst wall, and kill the host through their unceasing activity. In collateral work a papilloma was transplanted that was found protruding from the external auditory canal of a mouse which had received an intramuscular injection of methylcholanthrene many months previously. The tumor is now in its 5th generation, after 15 months. The growths it forms are of Type A. All of the papillomas are functioning tumors, with their own cells as the functioning product. Their papilliferous shape, when on the skin, is due solely to inability of their cells to gain space in other ways. Intrinsically they are keratomas. The papillomas do well after transfer to deep situations because the growth of their cells is indirectly promoted, through favoring local conditions. No direct promotion takes place like that when the cells of prostatic and mammary tumors are stimulated to multiply by hormones. Doubtless many agents act in both ways, that is to say by dual promotion.
PMCID: PMC2136781  PMID: 13481256
8.  Case report of complicated epidermoid cyst of the floor of the mouth: Radiology-histopathology correlation 
Qatar Medical Journal  2014;2014(1):12-16.
Epidermoid cysts, true dermoid cysts and teratoid cysts compose the spectrum of cystic teratomas, which are defined as neoplasms whose tissue are derivatives of more than one germ layer, foreign to that part of the body from which the tumor arises. Epidermoid cysts of the floor of the mouth are rare lesions and are much less common than dermoid cysts in the head and neck. This case reports a 43-year-old male patient who presented with a longstanding midline swelling in the submental region. Initial imaging was done using ultrasound followed by computed tomography (CT) scan. Biopsy was taken and revealed a cyst wall lined with epidermal squamous epithelium along with areas of focal ulceration suggesting chronic inflammatory changes of the wall of the epidermoid cyst.
There are characteristic and even pathognomonic imaging features of epidermoid cysts at the floor of the mouth in ultrasound and CT scan. Imaging has an important role in the surgical management plan according to the size and location of the cyst in relation to geniohyoid and mylohyoid muscles.
doi:10.5339/qmj.2014.2
PMCID: PMC4197368  PMID: 25320687
Epidermoid cyst; cystic teratoma; floor of mouth
9.  Interobserver Variability by Pathologists in the Distinction Between Cellular Fibroadenomas and Phyllodes Tumors 
Fibroepithelial lesions with cellular stroma are frequently termed cellular fibroadenomas although criteria for distinguishing them from a phyllodes tumor are vague and subjective. However, the clinical implications and surgical management for these 2 lesions may be different. We randomly selected 21 cases of fibroepithelial lesions sent in consultation to the senior author that were challenging to classify as cellular fibroadenoma or phyllodes tumor. One to 2 representative slides of each case along with patient age were sent to 10 pathologists who specialize in breast pathology. The World Health Organization criteria for phyllodes tumors and a diagnosis form were included with the study set. For the purposes of data reporting, fibroadenoma and cellular fibroadenoma are considered together. In only 2 cases was there uniform agreement as to whether the tumor represented a fibroadenoma or phyllodes tumor. Of the remaining 19 cases, if the diagnoses of fibroadenoma and benign phyllodes tumor were combined and separated from borderline and malignant phyllodes tumors, there was 100% agreement in 53% of cases and 90% agreement in 79% of cases. This study highlights the difficulty that exists in distinguishing some cellular fibroadenomas from phyllodes tumors even for pathologists who specialize in breast pathology. However, there appears to be considerable agreement when cellular fibroadenomas and benign phyllodes tumors are distinguished from borderline and malignant phyllodes tumors. Further studies are needed to determine if there is a clinically significant difference between cellular fibroadenomas and benign phyllodes tumors and how to better distinguish them from borderline and malignant phyllodes tumors.
doi:10.1177/1066896914548763
PMCID: PMC4352312  PMID: 25161205
fibroepithelial lesion; phyllodes tumor; cellular fibroadenoma
10.  Epidermal cyst in an unusual site: A case report 
Highlights
•Epidermal cysts can be located in any part of the body, though mainly on the face, torso, extremities and scalp, but they are rarely localized on the vulva.•Most of the vulvar epidermal cysts described so far have been localized on the clitoris; and circumcision procedures and trauma have been demonstrated as underlying causes.•Our patient, had not been previously exposed to trauma or undergone any surgical intervention.•Vulvar epidermal cyst should be considered in the differential diagnosis of vulvar mass.
Introduction
Epidermoid cysts can occur in a variety of locations including face, trunk, neck, extremities and scalp. Up to now, those vulvar epidermal cysts reported in the literature were localized on the labia majora and the clitoris. This is the first case of epidermal cyst reported on the labia minora.
Presentation of case
A 47-year-old, multiparous woman presented with a history of a palpable vulvar mass, without pain but causing difficulty in walking. The large mass was 6 cm in diameter and located in the left labium minus. The labial mass was surgically removed. The final pathologic diagnosis was a vulvar epidermoid cyst. The patient was discharged from hospital without any complications.
Discussion
Total surgical excision of the mass is more appropriate for definitive histopathological diagnosis and for the prevention of future development of complications. MRI is very important in the localization of the mass and relationship with other tissues regarding treatment planning of larger vulvar masses.
Conclusion
Epidermal cysts should be considered in the differential diagnosis of a vulvar mass.
doi:10.1016/j.ijscr.2015.01.001
PMCID: PMC4353988  PMID: 25658206
Epidermal cyst; Labium minus; Vulva; Vulvar tumor
11.  Composite Tumor Associating Trichoblastoma and Seborrheic Keratosis 
Annals of Dermatology  2015;27(5):601-604.
Seborrheic keratosis is a common benign epidermal tumor histologically composed of basaloid and squamous cells. It mainly occurs on the face, scalp, and trunk, and presents clinically as a well-circumscribed, brownish to black papule, nodule, or plaque. Trichoblastoma is a relatively rare benign, slow-growing tumor showing differentiation toward the primitive hair follicle. It clinically manifests as a solitary, skin to erythematous colored, well-circumscribed dermal nodule located predominantly on the head and neck with a predilection for the scalp. Histologically, a well-demarcated mass of follicular germinative cells that show various degrees of differentiation, arranged in lobules, sheets, and nests, is located in the dermis or subcutaneous fat layer. We report the case of a 28-year-old female patient with a solitary, 2.0×4.0-cm black plaque with a 0.7-cm skin-colored nodule on the scalp. Histologically, the entire black plaque had prominent hyperkeratosis, acanthosis, and papillomatosis with horn cysts. The central nodule showed well-circumscribed, various-sized dermal tumor lobules without a connection to the overlying epidermis. The lobular aggregation was composed of numerous basaloid epithelial nests and multiple primitive papillary structures with distinct peripheral palisading of nuclei. According to these findings, the scalp lesion was diagnosed as a composite tumor associating trichoblastoma and seborrheic keratosis.
doi:10.5021/ad.2015.27.5.601
PMCID: PMC4622895  PMID: 26512175
Composite tumor; Seborrheic keratosis; Trichoblastoma
12.  Eccrine Spiradenoma Arising in the Breast Misdiagnosed as an Epidermal Inclusion Cyst 
Korean Journal of Radiology  2011;12(2):256-260.
Eccrine spiradenomas are rare, benign, cutaneous tumors that originate in the sweat glands. Eccrine spiradenomas in the breast are very rare and only a few cases have been reported. We report here on the case of a 47-year-old woman with superficial masses in the breast and these masses had gradually increased in size during follow-up. They were confirmed to be an eccrine spiradenoma on pathologic examination. There have been a few reports about the radiologic findings of eccrine spiradenomas of the breast. This is the first case of an eccrine spiradenoma in the breast that was characterized by multiple imaging modalities, including mammography, ultrasonography and MRI. The lesion in our patient was first diagnosed as an epidermal inclusion cyst based on the imaging findings and the mass's superficial location. Although the mammographic and ultrasonographic imaging findings of eccrine spiradenomas and epidermal inclusion cysts are similar, the MRI findings are different between epidermal inclusion cysts and eccrine spiradenomas. Eccrine spiradenomas should be considered in the differential diagnosis of cutaneous and subcutaneous lesions of the breast.
doi:10.3348/kjr.2011.12.2.256
PMCID: PMC3052619  PMID: 21430945
Eccrine spiradenoma; Breast; Mammography; Ultrasound (US); Magnetic resonance (MR)
13.  Expression of hypoxia-inducible factor 1 alpha and its downstream targets in fibroepithelial tumors of the breast 
Breast Cancer Research  2005;7(5):R808-R818.
Introduction
Hypoxia-inducible factor 1 (HIF-1) alpha and its downstream targets carbonic anhydrase IX (CAIX) and vascular endothelial growth factor (VEGF) are key factors in the survival of proliferating tumor cells in a hypoxic microenvironment. We studied the expression and prognostic relevance of HIF-1α and its downstream targets in phyllodes tumors and fibroadenomas of the breast.
Methods
The expression of HIF-1α, CAIX, VEGF and p53 was investigated by immunohistochemistry in a group of 37 primary phyllodes tumors and 30 fibroadenomas with known clinical follow-up. The tumor microvasculature was visualized by immunohistochemistry for CD31. Proliferation was assessed by Ki67 immunostaining and mitotic counts. Being biphasic tumors, immunoquantification was performed in the stroma and epithelium.
Results
Only two fibroadenomas displayed low-level stromal HIF-1α reactivity in the absence of CAIX expression. Stromal HIF-1α expression was positively correlated with phyllodes tumor grade (P = 0.001), with proliferation as measured by Ki67 expression (P < 0.001) and number of mitoses (P < 0.001), with p53 accumulation (P = 0.003), and with global (P = 0.015) and hot-spot (P = 0.031) microvessel counts, but not with CAIX expression. Interestingly, concerted CAIX and HIF-1α expression was frequently found in morphologically normal epithelium of phyllodes tumors. The distance from the epithelium to the nearest microvessels was higher in phyllodes tumors as compared with in fibroadenomas. Microvessel counts as such did not differ between fibroadenomas and phyllodes tumors, however. High expression of VEGF was regularly found in both tumors, with only a positive relation between stromal VEGF and grade in phyllodes tumors (P = 0.016). Stromal HIF-1α overexpression in phyllodes tumors was predictive of disease-free survival (P = 0.032).
Conclusion
These results indicate that HIF-1α expression is associated with diminished disease-free survival and may play an important role in stromal progression of breast phyllodes tumors. In view of the absence of stromal CAIX expression in phyllodes tumors, stromal upregulation of HIF-1α most probably arises from hypoxia-independent pathways, with p53 inactivation as one possible cause. In contrast, coexpression of HIF-1α and CAIX in the epithelium in phyllodes tumors points to epithelial hypoxia, most probably caused by relatively distant blood vessels. On the other hand, HIF-1α and CAIX seem to be of minor relevance in breast fibroadenomas.
doi:10.1186/bcr1296
PMCID: PMC1242154  PMID: 16168127
14.  Multiple Giant Sebaceous Cysts of Scalp 
Sebaceous cyst is an epidermal cyst often found on the hairy areas of the body such as scalp, trunk and face. Though commonly encountered in surgical practice, its presentation as multiple giant sebaceous cysts over scalp is rare. However, in long standing cases malignant transformation has also been sparingly reported. We report a case of a 52-year-old male presenting with multiple large sized swellings on the scalp, seven in number. These were present since childhood and gradually progressed to the enormous size of largest measuring 10cm x 8cm. Excision of these cysts was undertaken and specimens were sent for histopathological examination which confirmed the nature of these cysts to be sebaceous cysts. No malignant changes were reported in any of the specimens. The patient was followed up and was doing well.
doi:10.7860/JCDR/2015/15125.6798
PMCID: PMC4668472  PMID: 26673123
Epidermal cyst; Malignant; Sebum
15.  A Case of Large Phyllodes Tumor Causing “Rupture” of the Breast: A Unique Presentation 
Introduction. Phyllodes tumors are rare fibroepithelial tumors which constitute less than 1% of all known breast neoplasms. The importance of recognizing these tumors lies in the need to differentiate them from fibroadenomas and other benign breast lesions to avoid inappropriate surgical management. We report a case of large phyllodes tumor which caused rupture of the breast and presented as an external fungating breast mass, a presentation which is exceedingly rare. Case Presentation. A 32-year-old female presented with a 1-year history of a mass in her right breast and eruption of the mass through the skin for the last 3 months. On physical examination, an ulcerated, irregular, and nodular mass measuring 9 × 8 cms was found hanging in the lower and outer quadrant of the right breast. Ultrasonography revealed an exophytic mass with heterogeneous echotexture and vascularity. Under general anesthesia, the tumor was excised. The resected specimen was 9.5 × 8.5 × 4.5 cm in size and the tumor was not invasive to the surrounding tissues. Histological examination confirmed a benign case of Phyllodes tumor. Conclusion. Clinicians should be aware of the myriad ways in which Phyllodes can present. A rapidly growing breast mass in a female should raise strong suspicion for Phyllodes. It is necessary to differentiate it from fibroadenomas to avoid inappropriate surgical management which may lead to local recurrence.
doi:10.1155/2013/871292
PMCID: PMC3666329  PMID: 23762692
16.  Molecular pathogenesis of progression and recurrence in breast phyllodes tumors 
Breast phyllodes tumors are rare fibroepithelial neoplasms that need to be distinguished from the common morphologically similar fibroadenomas, because phyllodes tumors can recur and progress to malignancy. Their potentially recurring and metastasizing behavior is attributed to their stromal characteristics, for which categorization between benign, borderline and malignant tumors have not been universally established. Previous clonality studies revealing monoclonal stromal cells versus a polyclonal epithelial component theorized that phyllodes tumors are mainly stromal neoplasms, possibly arising from fibroadenomas. More recent chromosomal imbalances in both epithelium and stroma have challenged this theory to favor neoplasia of both epithelium and stroma, with initial interdependence between the two components. Inverse correlations between epithelial and stromal overexpression for various biological markers like estrogen receptor, p53, c-kit, Ki-67, endothelin-1, epidermal growth factor receptor, heparan sulfate, in addition to findings of epithelial Wnt signalling with stromal insulin growth factors and beta-catenin expression, suggest an initial epithelial-stromal interdependence at the benign phase. Upon progression to malignancy, the stroma is hypothesized to assume an autonomous growth overriding any epithelial influence. Frequent genetic alterations are chromosomal gains of 1q and losses at chromosome 13. Acquisition of new genetic imbalances within the tumor consistent with intratumoral heterogeneity, and subclones within histologically benign phyllodes tumors that recur or metastasize are the current theories explaining these tumors' unpredictable clinical behavior.
PMCID: PMC2776292  PMID: 19966935
Molecular pathogenesis; phyllodes tumors; epithelial-stromal interactions; biological markers; genetic alterations; subclones
17.  Giant epidermal cyst in the posterior neck developing over 40 years: A case report 
Conventional epidermal cysts are generally small, slow-growing, non-tender, dome-shaped lesions. An epidermal cyst is usually asymptomatic until it is infected or enlarged to the extent that it causes damage to adjacent anatomical structures. However, few cases of giant epidermal cysts in the neck have been reported. The present case reports a giant epidermal cyst in the posterior neck, which grew to an extremely large size for >40 years without inflammation or rupture, and was misdiagnosed as a large soft tissue neoplasm. The patient exhibited depression and developed social anxiety due to the negative cosmetic consequences of the large mass. The patient underwent excision of the mass. At the follow-up examination two years postoperatively, there were no local recurrence and the psychiatric symptoms of the patient were completely resolved. To the best of our knowledge, a giant epidermal cyst growing for >40 years has not previously been reported.
doi:10.3892/etm.2013.1383
PMCID: PMC3861182  PMID: 24348807
giant epidermal cyst; posterior neck; psychiatric symptom; cosmetic problem
18.  Giant benign phyllodes tumor with lactating changes in pregnancy: a case report 
Gland Surgery  2015;4(4):339-343.
Background
Phyllodes tumor in pregnancy is extremely rare. We present the first case ever reported of a giant benign phyllodes tumor with lactating changes during pregnancy.
Presentation of case
A 36-year-old female patient at the 32nd week of pregnancy presented with a huge mass in left breast for 5-6 months. Physical examination revealed a firm palpable 20 cm mass occupying the whole left breast. Ultrasound guided core needle biopsy demonstrated a fibroepithelial lesion suggestive of benign phyllodes tumor. She was scheduled for mastectomy three weeks after birth delivery. The microscopic examination of the resected specimen revealed the mass consisted mainly of lactating components with areas of hypercellular stroma and epithelial proliferation in leaf-like pattern. Finally, the pathological report confirmed a giant benign phyllodes tumor with lactating changes and frees all surgical margins.
Discussion
Phyllodes tumor in pregnancy is rare with just nine cases reported. It is unknown if the rapidly growing mass in pregnant patient is hormone-dependent. This is the first report of a giant benign phyllodes tumor with lactating changes in pregnant patient. In these large phyllodes tumors, heterogeneous stromal components are common. It is occasionally difficult to distinguish between benign phyllodes tumor with lactating changes and lactating adenoma. Because the surgical treatment and local recurrence rate are different between these two diseases, we need to clearly differentiate benign phyllodes tumors from other benign breast diseases.
Conclusions
This case emphasizes the heterogeneity of giant phyllodes tumors. Therefore, it is important to thoroughly examine the resected specimen for possible additional components. The key point is that adequate and clear surgical margins in any phyllodes tumors must be achieved to reduce local recurrence.
doi:10.3978/j.issn.2227-684X.2015.01.09
PMCID: PMC4523627  PMID: 26312220
Giant phyllodes tumor; benign phyllodes tumor; pregnancy; lactating changes; lactating adenoma
19.  Epidermal Cyst of the Breast Treated by Vacuum-Assisted Biopsy 
International Surgery  2013;98(1):65-69.
A 38-year-old woman presented for evaluation of a firm mass (measuring 20 × 20 mm) in the upper outer quadrant of her left breast. On the basis of the clinical and radiologic findings, we diagnosed a benign breast tumor and scheduled removal by a hand-held vacuum-assisted biopsy device (VABD) under ultrasonographic guidance. Because the first specimen removed from the tumor was white, flaky, and waxy material, we strongly suspected that the lesion was an epidermal cyst. We continued VABD treatment until the tumor was invisible on real-time ultrasonography. Histologic examination demonstrated that the tumor was composed of mature stratified squamous epithelium and laminated layers of keratin, findings consistent with a diagnosis of epidermal cyst. These cysts rarely occur in the breast and are sometimes difficult to distinguish from breast cancer. To our knowledge, this is the first report of an epidermal cyst treated by VABD.
doi:10.9738/CC74.1
PMCID: PMC3723168  PMID: 23438279
Epidermal cyst; Breast; Vacuum-assisted biopsy device (VABD)
20.  A Subset of Malignant Phyllodes Tumors Express p63 and p40 
Breast phyllodes tumors are rare fibroepithelial neoplasms of variable grade, and one key differential of malignant phyllodes on core biopsy is sarcomatoid carcinoma. p63 is reported to be sensitive and specific for sarcomatoid carcinoma, with rare expression in phyllodes in limited series. The p63 deltaNp63 isoform, p40, is postulated to be more specific for squamous differentiation but has not previously been evaluated in breast phyllodes or sarcomatoid carcinoma. Tissue microarrays containing 34 unambiguous phyllodes tumors (10 benign, 10 borderline, 14 malignant), 13 sarcomatoid carcinomas, and 10 fibroadenomas were labeled by immunohistochemistry for p63, p40, CD34, and cytokeratins AE1/AE3, 34betaE12, and CK8/18. No borderline phyllodes tumor, benign phyllodes tumor, or fibroadenoma labeled with p63, p40, or cytokeratin. However, p63 labeled 57% malignant phyllodes tumors and 62% sarcomatoid carcinomas, and p40 labeled 29% malignant phyllodes (focal) and 46% sarcomatoid carcinomas. Among established markers, cytokeratins labeled 21% malignant phyllodes tumors (focal) and 100% sarcomatoid carcinomas. CD34 labeled 57% malignant phyllodes tumors and no sarcomatoid carcinomas. Focal p63, p40, and cytokeratin labeling can be seen in malignant phyllodes tumors but not in lowergrade fibroepithelial lesions, and immunoreactivity with these markers alone is not diagnostic of sarcomatoid carcinoma on core needle biopsy. In the differential diagnosis of malignant phyllodes, p40 is a more specific but less sensitive marker of sarcomatoid carcinoma than p63. These results are consistent with the sarcoma literature in which p63 labeling has been increasingly reported and suggest caution in classifying malignant spindle cell tumors of the breast on core biopsy.
doi:10.1097/PAS.0000000000000301
PMCID: PMC4373607  PMID: 25046342
breast tumor; p40; p63; phyllodes tumor; sarcomatoid carcinoma
21.  A subset of malignant phyllodes tumors harbors alterations in the Rb/p16 pathway 
Human pathology  2013;44(11):2494-2500.
Summary
Breast phyllodes tumors are fibroepithelial neoplasms with variable risk of aggressive local recurrence and distant metastasis, and the molecular pathogenesis is unclear. Here, we systematically study p16 and Rb expression in 34 phyllodes tumors in relation to proliferation. Tissue microarrays were constructed from 10 benign, 10 borderline, and 14 malignant phyllodes (5 cores/tumor) and from 10 fibroadenomas (2 cores/tumor). Tissue microarrays were labeled by immunohistochemistry for p16, Rb, and Ki-67 and by in situ hybridization for high-risk human papillomavirus. Cytoplasmic and nuclear p16 were scored by percentage labeling (0%-100%, diffuse >95%) and intensity. Nuclear Rb was scored by percentage labeling (0%-100%, diffuse >75%) and intensity. p16 and Rb labeling were repeated on whole sections of cases with Rb loss on the tissue microarray. Twenty-nine percent (4/14) malignant phyllodes showed diffuse strong p16 labeling with Rb loss in malignant cells (diffuse p16+/Rb−), whereas 21% (3/14) malignant phyllodes showed the reverse pattern of p16 loss with diffuse strong Rb (p16−/diffuse Rb+). Results were consistent between tissue microarrays and whole sections. No borderline phyllodes, benign phyllodes, or fibroadenoma showed diffuse p16+/Rb− or p16−/diffuse Rb+ phenotypes. No cases contained high-risk human papillomavirus. Average Ki-67 proliferation indices were 15% in malignant phyllodes, 1.7% in borderline phyllodes, 0.5% in benign phyllodes, and 0% in fibroadenoma. Ki-67 was highest in malignant phyllodes with diffuse p16+/Rb− labeling. In summary, 50% malignant phyllodes display evidence of Rb/p16 pathway alterations, likely reflecting p16 or Rb inactivation. These and other mechanisms may contribute to the increased proliferation in malignant phyllodes relative to other fibroepithelial neoplasms.
doi:10.1016/j.humpath.2013.06.009
PMCID: PMC3998645  PMID: 23916291
p16; Rb; Phyllodes tumor; Breast; Fibroepithelial neoplasm
22.  A Case of an Undifferentiated Squamous Cell Carcinoma Arising from an Epidermal Cyst 
An epidermal cyst is a common benign subcutaneous tumor and rarely develops malignancy. We report a case of an undifferentiated cutaneous squamous cell carcinoma (SCC) that arose from an epidermal cyst on the left side of the neck. The epidermal cyst had rapidly increased in size and presented cauliflower-like tumor. Histological study revealed undifferentiated squamous cell carcinoma that was arising from the epidermal cyst.
doi:10.1155/2013/469516
PMCID: PMC3582051  PMID: 23476821
23.  Breast Lumps: A 21-Year Single-Center Clinical and Histological Analysis 
Objective:
To review the presentation and histological diagnosis of breast lumps of patients seen in Trans Ekulu Hospital Enugu Southeastern Nigeria from 1993 to 2013 in a period of 21 years.
Materials and Methods:
This is a retrospective study covering a period of 21 years. Case notes of patients containing clinical information and their histology reports were studied.
Results:
Only 38% of the patients came within 3 months of finding lumps in their breast. One hundred and thirty-seven patients (83%) had benign disease, i.e., fibroadenoma, mammary dysplasia, cysts, adenomas, tuberculosis, phyllodes tumor, mastitis, and lipoma. Only 16.9% i.e., 28 patients had breast cancer, out of which two females were in their 20s, and three were males.
Conclusions:
Benign breast diseases, i.e., fibroadenoma, fibroadenosis, cysts, adenomas, tuberculosis, phyllodes, mastitis, and lipoma are the commoner breast diseases in our locality.
doi:10.4103/1117-6806.127111
PMCID: PMC3953633  PMID: 24665202
Breast lumps; biopsy; Enugu; single centre; Southeastern Nigeria
24.  Rapidly progressive multifocal phyllodes tumour of the breast: A case report and review of the literature☆ 
INTRODUCTION
Malignant transformation of a phyllodes tumour is a rare form of breast cancer, accounting for just 0.5% of all breast cancer cases.1
PRESENTATION OF CASE
We report a case of a 49 year old female with rapidly progressive, multifocal disease. She initially presented with two giant fibroadenomas which were excised. She represented eight months post surgery with two new lesions in the same breast, one suspicious, one suggestive of fibroadenoma. Biopsy was borderline. Surgery was therefore scheduled for wide local excision. At localisation two weeks later, at least eight lesions were seen on ultrasound scan. Three were removed as histology was at this point unknown to conserve the breast. Histology revealed intermediate grade DCIS, benign Phyllodes and borderline/malignant phyllodes. She was scheduled for mastectomy and immediate Strattice reconstruction. An MRI was performed pre-operatively to ascertain extent of disease. Two weeks post localisation, 13 lesions were identified. The right breast was entirely unaffected. Surgery interval was three weeks and final histology revealed 18 lesions, ranging from fibroadenoma through to borderline/malignant phyllodes with an incidental papilloma.
DISCUSSION
This is the first report of such rapid progression of disease, with 16 new lesions, of varied histology, developing in just an eight week period.
CONCLUSION
This case highlights the difficulty of forming a clear diagnostic and therapeutic pathway in this highly variable disease. Arguments for over and under treating these patients remain but those with any borderline/malignant potential have to be removed as recurrence is both common and aggressive, with a clear surgical margin the only proven protective factor.
doi:10.1016/j.ijscr.2013.04.042
PMCID: PMC3785922  PMID: 24013041
Breast; Phyllodes; Cancer; Surgery; Multifocal
25.  Squamous cell carcinoma arising from an epidermal inclusion cyst: A case report 
Context:
Cutaneous epidermal cysts are common lesions, but fortunately, malignant transformation of their epithelium is rare. There are few case reports in the literature concerning malignant transformation of an epidermal cyst into squamous cell carcinoma. We present a case of squamous cell carcinoma arising from an epidermal inclusion cyst and describe the clinical and histopathologic findings.
Case Report:
A tumour measuring 1.5cm was surgically excised. Based on the histopathologic findings of the tumour, this case was diagnosed as squamous cell carcinoma that arises in an epidermal cyst. Malignant change had not been suspected until histological examination revealed it. Nine months after tumour resection, the patient is free of disease.
Conclusion:
malignant transformation of an epidermal inclusion cyst is rare; this case illustrates the importance of routine histology in excision of epidermal cysts.
PMCID: PMC3354388  PMID: 22624113
Epidermal cyst; carcinoma; histopathology

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