Papilloma and Papillomatosis

A papilloma is a benign growth in breast ducts, which has ‘finger-like‘ fronds, and often completely blocks the duct. They are composed of ‘mammary epithelium’, which are the cells that comprise most of the breast duct-wall linings.

Because it is a solid lump of new-cell growth (not a cyst), an undiagnosed papilloma can at first seem suspicious for breast cancer until it is properly analyzed. A papilloma itself is benign, but they are suspicious of a situation where cancer might develop, especially when they seem to be occuring in multiples. Papillomas tend to develop in women in the 35-55 age range.

Is a breast papilloma related to the human papilloma virus,HPV?

Intraductal (breast) papillomas are not at all related to HPV, not related to ‘warts’, which occur and skin surfaces and are caused by exposure to the Human Papilloma Virus (HPV). They simply share the name because they have similar features.

Hector Hector
Good to know, it’s not a wart.


Billy Billy
Or a butterfly.



 
 

benign breast papilloma

Talking Moose
Talking Moose
You REALLY have to use your imagination, to make that 2D histology image, visualize in your 3D mind as finger-like fronds.



 
 

Breast intraductal papilloma symptoms

A papilloma can present as a small ‘outward curved’ bump, and it can either be growing on the surface of the breast or within the breast ducts themselves and visible only on mammography or by a microscope.

A papilloma will generally form right around or below the nipple. A woman may discover a small lump herself, and often a clinical physician can find a tumor just beneath the surface through delicate palpation (feeling and pressure).

Papillomas can also be painful.

Jessica Jessica
So pain doesn’t mean cancer. Papilloma is just one kind of benign thing that can have pain.



 
 
A papilloma will usually involve a nipple discharge, sometimes of serous fluid but sometimes with blood as well. ( About 1/2 of the time the nipple discharge contains blood).

Dr. Halls Dr. Halls
So, whether or not you see blood in the discharge, it doesn’t change the risk.



 
 

Sometimes nipple discharge is called “pathological nipple discharge” or ‘PND’, and this symptom accounst for about 5% of all women who attend breast cancer screening clinics, and between 40-70% of women who present with this symptom (PND) end up being diagnosed with papilloma. Sometimes, however, pathological nipple discharge is associated with either ‘in situ‘ or invasive breast cancer, so it is a serious symptoms that has to be fully investigated. The rate of PND associated with breast cancer is hard to know for sure; some studies place it at over 20%, but a large, comprehensive study would probably place the rate considerably lower.

Various types of papillomas of the breast

There are two basic ‘categories‘ of breast papilloma development: Those which occur as ‘solitary‘, or those which occur in ‘multiples‘. The solitary papillomas are more prone to nipple discharge, and tend to involve a papillary epithelial growth which has ‘punctured’ a major breast duct just below the nipple. Generally speaking, solitary papillomas are benign and not worrisome. The tumor might be drained by excision or by needle aspiration, (and given a histological evaluation just to be sure), and most of the time will not even required routine-scheduled follow-up. Many physicians don’t even consider a solitary papilloma as a ‘true disease’ process.

Dr. Halls Dr. Halls
I’m in the ‘not a disease’ camp. Lots of things are variable in people. Extra thick hair, smooth or blemished skin are examples. I think of a small solitary papilloma in a duct, like that.



 
 

Multiple papillomas, or Papillomatosis

Multiple breast papillomas present a different, greater risk and management context. Here the tumors occur deeper with the breast and probably will not cause nipple discharges. Multiple papillomas form a subset of about 10% of all intraductal papillomas, and also tend to be seen more frequently in younger women. Papillomatosis areas are quite often ‘bilateral’ (occuring in both breasts). Sometimes the physical ‘placement’ of one of a multiple of papillomas will be given a particular name. “Central” papillomas grow deeper within the breast, while “peripheral’ papillomas are growing toward the outer edges of the breast. Some physicians argue that there needs to be at least five clearly separate papillomas within a given segment of breast tissue in order for the tumor to be termed ‘papillomatosis’. Multiple papillomas are more suspicious for subsquent breast cancer development than solitary papillomas.

Breast Papilloma may present with or without ‘atypia’

When a papilloma tissue sample is sent for microscopic evaluation, the pathologist may be looking for signs of ‘atypia‘. Sometimes, within the context of the presentation of ‘multiple’ papillomas, cellular atypica may already be present or may develop over time. These atypical cellular features may include hyperchromatic nuclei, marked nuclear atypia, cribriform patterns, a monotonous cell population, and absent supporting stroma. When enough atypical features are present, the phyicians may begin to classify the papilloma as ‘atypical ductal hyperplasia‘ or ADH, which a more serious, higher-risk diagnosis, and will be screened and treated more aggressively from that point on.

Juvenile Papillomatosis (JP)

Papillomatosis or ‘multiple papillomas’ tends to effect a slightly younger age group then solitary papillomas, but sometimes the condition can effect very young women, even as young as 10 years old. The mean age of diagnosis age tends to be in the early 20s. This ‘juvenile papillomatosis’ often includes a painless mass that is first dismissed as fibroadenoma.

Juvenile papillomatosis tends to have many features of atypical hyperplasia, and also some cyst development. Juvenlie papillomatosis is not breast cancer, but there is increased risk for breast cancer development, especially if it is bilateral. Family history also tends to play a role in increased risk or tendency or papillomatosis to develop into breast cancer. There is even some evidence to suggest that a young patients female relatives might be more succeptible to breast cancer development than the average population, though no one knows why this is.

Do Women with breast papilloma have an increased risk of breast cancer?

Any kind of proliferative cell growth in the breast raises concerns of occult breast cancer or increased risk for future breast cancer development. Fibrocystic changes of any sort are thought to confer a slightly increased risk of breast cancer development over the long term, but only slighly higher than for the general population. A solitary papilloma is considered to be benign, and the only increased risk of breast cancer would be that same, slight increase for all women who show any benign fibro-cystic change. Multiple papillomas, however, are associated with increased risk for breast cancer development, but still very low. If any of the papillomas show ‘atypical’ cells or cell formations, the risk is significantly higher, and we may in fact be speaking about a different diagnosis altogether, i.e. atypical ductal hyperplasia.

Papilloma may ‘conceal’ an undiagnosed breast cancer

However, recent studies have pointed to diagnostic and assement innaccuracies associated with papillomas and breast cancer risk. It is now suspected that most instances of papilloma and papillomatosis which have ‘evolved’ or ‘developed’ into breast cancer, were actually breast carcinoma to begin with and simply under-diagnosed. Where there is strong correlation between mammographic studies and microscopic studies that convincingly point to a benign tumor, there is very low risk of subsquent breast cancer appearance. In any event, annual follow-up for multiple papillomas is a prudent course of action.

breast papilloma ductogram

Dr. Halls Dr. Halls
This picture is a ductogram. I used to do them years ago, but stopped because they caused more uncertainty and more surgeries because of uncertainty, than I liked.



 
 

Imaging and diagnostic features of breast papilloma

Mammograms and ultrasounds are not necessarily that useful in diagnosing a papilloma. A mammogram will generally be performed regardless as a percaution in any lesion involving bloody discharges, but intraductal papillomas do not tend to show up well on a mammogram.

Tanya Tanya
Darn mammograms. Showing nothing, meanwhile a bloody nipple discharge keeps happening.



 
 

Papillomas tend to be small, and unless there is a large suspected ‘fat’ element or a somewhat larger lump, the breast mammogram will probably look normal. Ultrasound also does not reliably diagnose a papilloma. Ultrasound is generally used to get a reading on the relative amounts of fluid, solid, and fat elements in lesion, and can readily determine is a suspected lesion is a benign cyst (fluid filled). Papillomas are generally non-liquid but do occasionally appear as solid nodules within a fluid-filled duct, and some papillomas may present with cystic elements.

Tanya Tanya
Darn ultrasound. Why does this fail for papillomas?


Dr. Halls Dr. Halls
Because behind the nipple where all the ducts converge, everything looks like a duct, even a small papilloma inside a duct.



 
 

Breast MRI can reveal ‘hidden’ views, but cannot reliably distinguish benign from malignant cells within a papilloma

MRI is an extremely senstive diagnostic imaging tool and can sometimes reveal features of a papilloma ‘hidden’ to other views, but there is quite a range in possible appearances of a papilloma. MRI might reveal some ‘atypical’ or irregular enhancements that cannot reliably be distinquished from malignant cell growth, so biospy will be needed anyways.

Dr. Halls Dr. Halls
In other words, because MRI can show all sorts of unexplainable stuff..


Hector Hector
like, what is that enhancement all over the place?


Billy Billy
… the radiologist might have no clue and guess.. “could be fibrocystic disease”..


Dr. Halls Dr. Halls
and you might end up being sent for an unnecessary biopsy.


Talking Moose
Talking Moose
Getting an MRI for a nipple discharge, is like asking a barber if you need a haircut, even if you don’t really need one, you’re probably going to end up getting one.



 
 

But, if MRI shows nothing, that’s helpful, but expensive reassurance. MRI might show the total absence of atypical features surrounding the papilloma is that is the case, and this can be very reassuring for a patient. However, given the high cost and sub-optimal specificity, MRI is unlikely to be used for most suspected breast papillomas.

Breast Ductography

Breast ductography is an established diagnostic technique that is sometimes use for women who present with nipple discharges. Ductography (also called galactography or ductogalactography) basically involves injecting a ‘contrast enhancing’ die or substance directly into the breast ducts and then performing an X-Ray. This allows the physician to follow the course of fluids through the ducts and determined where there is any blockage.

A simple, solitary papilloma will quite easily be observed as a ‘blocked duct’.

Dr. Halls Dr. Halls
I don’t think it’s EASY. You see a blocked duct, if you are lucky, and if you Do see a blocked duct, you’re still just guessing at what blocked it.



 
 

Multiple papillomas can also be observed as absent or sub-segmental distribution of fluid in the branching ducts; there will be a typical and identifiable pattern. Ductography might also detect the presence of malignant processes, through distortions, narrowing, and obstruction of various ducts. However, ductography has considerable limitations at arriving at a definitive diagnosis, so it is no longer a widely practiced procedure.

Microscopic features of breast papilloma

Breast papillomas will typically have a characteristic ‘arboriform’ ( tree like, or frond like) structure with a central fibrovascular core. ( combination of fibrous tissues and blood supply elements) The lesion may also have an inner myoeptihelial and outer luminal epithelial layer. The epithelial elements might show generic-type hyperplasia, apocrine metaplasia, and rarely squamous metaplasia. Sclerosis, or hardening of the fibrovascular core is common, as well as complete or partial obliteration of the duct lumen (total blockage). When the hardening and blockage aspects seem to be the dominant features of the tumor, it might be classified as ductal adenoma. Microscopic analysis of a suspected papilloma or follow-up evalution of a confirmed papilloma might also reveal atypical hyperplasia features, or even in situ carcinoma, (DCIS) and will be classified and treated accordingly.

breast papilloma

Talking Moose
Talking Moose
Hey, this picture is way better than the one at the beginning. It looks like fronds!, pieces of a fern leaf.



 
 

Is there any relationship between papilloma and the micropapillary form of DCIS?

When confronted with ‘papilloma-like’ symptoms, a pathologist needs to make a differential diagnosis between benign papilloma on the one hand, and malignant micropapillary DCIS on the other. Both diseases have similar frond-like features. The ‘Transitional epithelium’ in some less-typical papillomas can resemble micropapillary DCIS cells.

However, there does not appear to be any relationship between papilloma and micropapillary dcis. One can be misdiagnosed as the other, and sometimes carcinoma can arise ‘de novo’ (on its own, from the beginning) from the same areas as a papilloma, but there appears to be no ‘disease-related’ connection between them. A papilloma is not part of a micropapillary DCIS scenerio and does not ‘evolve into’ micropapillary DCIS or papillary breast carcinoma.

Treatment and management of breast papilloma

Solitary papillomas, if there are no functional complications or atypical features, will often just be left alone. If there is nipple discharge, the lesion will first be drained, and quite likely surgically excised. Often a small incision is made at the edge of the areola and the resulting scar tissue is virtually unnoticeable.

If there are no atypical features, there is no need to rush into surgical removal of breast papillomas

Treatment of multiple papillomas can be a bit of a grey area and judgement call. Since the only real treatment for papillomatosis ( multiple papillomas) will be mastectomy, this is a decision which tends to be delayed as much as possible. Papillomatosis will be carefully followed-up by annual checkups. If there is no evidence of atypical or malignant processes, there really is no clear reason to do anything.

Where there an associated bloody nipple discharge with papillomatosis, that does tend to indicate a more suspicious situation and if it is an ongoing thing, mastecomy might be considered. However, there are new treament techniques such as the “microdochectomy”, which is the surgical excision of the major effected breast duct and not the entire breast. That might be a prudent treatment option for localized, suspicious papillomas with discharges.

References

  1. Dzodic, R., Stanojevic, B., Saenko, V., Nakashima, M., Markovic, I., Pupic, G., Buta, M., Inic, M., Rogounovitch, T., Yamashita, S.:Intraductal papilloma of ectopic breast tissue in axillary lymph node of a patient with a previous intraductal papilloma of ipsilateral breast: a case report and review of the literature. Diagnostic Pathology 2010, 5:17
  2. Ichihara S, Ikeda T, Kimura K, Hanatate F, Yamada F, Hasegawa M, Moritami S, Yatabe Y: Coincidence of Mammary and Sentinel Lymph Node Papilloma. Am J Surg Pathol 2008, 32:784-782
  3. Oyama T, Koerner FC: Noninvasive papillary proliferations.Semin Diagn Pathol 2004, 21(1):32-41.
  4. Carter D: Intraductal papillary tumours of the breast, a study of 78 cases. Cancer 1977, 39:1689-1692.
  5. Renshaw, A., Derhagopian, RP., Tizol-Blanco, DM., Gould, EW., Papillomas and Atypical Papillomas in Breast Core Needle Biopsy Specimens. Am J Clin Pathol 2004;122:217-221
  6. Ioffe OB, Berg WA, Silverberg SG. Analysis of papillary lesions diagnosed on core needle biopsy of the breast: management implications Mod Pathol. 2000;13:23A.
  7. Sarakbi, W., Worku, D., Escobar, PF., Mokbel, K.:Breast papillomas: current management with a focus on a new diagnostic and therapeutic modality. International Seminars in Surgical Oncology 2006, 3:1
  8. Mckinney CD, Fechner RE: Papillomas of the breast. A histologic spectrum including atypical hyperplasia and carcinoma in situ. Pathol Annu 1995, 30(Pt 2):137-78.
  9. Rosen PP, Lyngholm B, Kinne DW, et al.: Juvenile papillomatosis and family history of breast carcinoma. Cancer 1982, 49:2591
  10. Paterok EM, Rosenthal H, Sabel M: Nipple discharge and abnormal galactogram. Results of a long-term study (1964–1990). Eur J Obstet Gynecol Reprod Biol 1993, 50:227-34..
  11. Atkins H, Wolff B: Discharge from the nipple. BJS 1964, 51:602-606.
  12. Lewis JT, Hartmann LC, Vierkant RA, Maloney SD, Shane Pankratz V, Allers TM, Frost MH, Visscher DW. An analysis of breast cancer risk in women with single, multiple, and atypical papilloma. Am J Surg Pathol. 2006 Jun;30(6):665-72.
  13. Ali-Fehmi R, Carolin K, Wallis T, Visscher DW.. Clinicopathologic analysis of breast lesions associated with multiple papillomas. Hum Pathol. 2003 Mar;34(3):234-9.
  14. Hill, C. Yeh, I-tien. Myoepithelial Cell Staining Patterns of Papillary Breast Lesions From Intraductal Papillomas to Invasive Papillary Carcinomas. Am J Clin Pathol 2005;123:36-44
  15. Kraus FT, Neubecker RD. The differential diagnosis of papillary tumors of the breast. Cancer. 1962;15:444–455.

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