ORIGINAL ARTICLE – BREAST ONCOLOGY

Relationship Between the Lymphatic Drainage of the Breastand the Upper Extremity: A Postmortem Study

David Pavlista, MD, PhD1 and Oldrich Eliska, MD, DSc2

1Oncogynecologic Center, Department of Obstetrics and Gynecology, First Faculty of Medicine, Charles University in

Prague and General University Hospital, Prague, Czech Republic; 2Institute of Anatomy, First Faculty of Medicine,

Charles University in Prague, Prague, Czech Republic

ABSTRACT

Background. This anatomic study details the lymphatic

drainage of the upper extremity (UE) and breast, as well as

its course in the axilla and its relation to axillary reverse

mapping. Two aspects important for breast cancer surgery

were followed: connection between the lymphatics of the

UE and breast, and the possible cause of lymphedema of

the UE after sentinel node (SN) biopsy.

Methods. Patent blue dye was injected bilaterally in 23

cadavers with no history of breast carcinoma to simulta-

neously visualize the lymphatics of the UE and breast.

After visualization and dissection of the lymphatic vessels

and nodes, a record of their routes was made. A scheme of

superficial UE and breast lymphatics was constructed.

Results. After application of color contrast to the UE, 2–4

main afferent collectors were shown. As opposed to cranial

and medial collectors, caudal collectors diverged from the

axillary vein and entered the caudal axilla. In five (10.8 %)

cases, the caudal collector entered a node, which was

considered to be the SN of the breast. In six (13 %) cases,

the SN of the breast and SNs of the UE were found in close

proximity (up to 1.5 cm).

Conclusions. Lymphatic drainage of the UE and breast are

closely related in the caudal part of the axilla. SN groups

for the UE and breast share connections in 24 % of cases,

which could explain lymphedema after surgery if damaged.

Additional studies are needed to further improve our

understanding of the lymphatic drainage of the UE and

breast.

Axillary lymph node metastasis is a strong, negative

prognostic factor in patients with breast cancer that sig-

nificantly modifies their further treatment. In the past,

axillary staging in breast cancer was performed by exen-

teration of the axilla, which involved the removal of all

fatty lymphatic tissue from all three axillary levels.

Because of significant postoperative morbidity (lymphe-

dema, paresthesia, limitations of upper extremity mobility),

this method was gradually replaced by less radical dis-

section of the axilla in which nodes are removed from the I

and II axillary levels according to Berg.1 The incidence of

the most serious psychosocial and economic complication,

lymphedema, then fell from 40 to 20 %. Unfortunately,

with subsequent radiotherapy after dissection of axilla, the

risk of developing postoperative lymphedema of the upper

extremity doubles.2 With the gradual introduction of

screening programs for breast cancer and the increased

incidence of breast cancer in the first stage at the time of

diagnosis, sentinel node biopsy for axillary staging has

gradually established itself as the method of choice. For

patients who do not have sentinel node metastases, dis-

section of the axilla is not performed and the risk of

developing lymphedema is greatly reduced.3 Surprisingly,

however, even with this minimally invasive method aided

by the detection and extirpation of the sentinel lymph node

with the use of lymphatic mapping (subcutaneous appli-

cation of patent blue and radioisotopes), the incidence of

lymphedema described is 3–13 % of cases.4,5

The need to further reduce the risk of lymphedema has

spurred the development of methods to identify and pre-

serve the lymphatics that drain the upper extremity and

pass through the axilla. Axillary reverse mapping (ARM) is

one such method that images the lymphatic drainage of the

upper extremity to facilitate the preservation of lymphatics

in the course of invasive axillary procedures.6,7 It is based

on the assumption that lymphedema is caused by limited

� Society of Surgical Oncology 2012

First Received: 7 January 2012;

Published Online: 24 April 2012

D. Pavlista, MD, PhD

e-mail: daxpa@seznam.cz

Ann Surg Oncol (2012) 19:3410–3415

DOI 10.1245/s10434-012-2363-x

lymph drainage from the upper extremity after interruption

of lymphatics (lymphatic collectors) traversing the axilla.8

Another assumption is that upper extremity lymphatics are

not involved in the metastasis of breast carcinoma.9 This

assumes that the lymphatic drainage of the breast and upper

extremity is functionally and anatomically separate, and

can be reliably detected operatively. This conceptually

simple and elegant operative solution is supported by the

results of several recently published studies.7,10,11

LYMPHATIC DRAINAGE OF THE BREAST

Because of the problems of imaging lymphatic vessels

(collectors), the anatomy of the lymphatic system of the

breast was not described until the 18th century. The first to

describe the anatomy of the breast lymphatics was Cruik-

shank12 in 1787. In 1874, Sappey13 described the superficial

system of lymphatic vessels in the subcutaneous breast, the

subareolar plexus, which is connected with the deep system

of lymphatic vessels draining the breast itself. According to

Sappey, lymph from these two systems is drained primarily

by collectors centrifugally to axillary nodes. The findings of

Sappey became the theoretical basis for further study of the

lymphatic system of the breast. In 1903, Poirier and Cuneo

summarized the results of Sappey’s work and supplemented

the results of their study with lymphatic mapping using oil

pigments, a method suggested by the Romanian anatomist

Dumitru Gerota.14 Borgstein et al.15 reported that the lym-

phatic drainage of the skin covering the mammary gland

along with drainage of the mammary parenchyma functions

as an independent biologic unit and its lymphatic system

removes lymph preferentially to certain (sentinel) lymph

nodes in the axilla. According to Borgstein, this arrange-

ment is the basis in the common ectodermal origin of both

tissues. Indeed, the results of anatomic studies reported by

other authors support the contention that the skin and sub-

cutaneous tissue of the breast are drained primarily to the

axilla and lymph vessels drain lymph in the breast paren-

chyma centripetally over Sappey’s subareolar plexus.16,17

Clinically proven knowledge of the lymphatic drainage of

the breast has led to the widespread introduction of sentinel

node biopsy in patients with breast cancer and reduced

radical procedures in the axilla.18 Recently, the issue of

lymphatic drainage in breast cancer after chemotherapy has

been highly debated, where the success of lymphatic map-

ping and sentinel node identification may be decreased.19

Lymphatic Drainage of the Upper Extremity

Lymphatic drainage of the upper extremity consists of

two main parts, the superficial and deep lymphatic net-

works, which are predominantly drained to the axillary

nodes.11 In a certain percentage of cases, the lateral (radial)

plexus is partially drained to the supraclavicular nodes

(Mascagni plexus). Superficial lymphatics divert lymph to

the axillary nodes (lateral, central and also partially sub-

scapular). The deep lymphatic system removes *20 % of

lymph from the upper extremity. Its vessels run along the

brachial and axillary veins to the lateral, and partially

central axillary nodes, and mainly to the infraclavicular

nodes. Under normal circumstances, there are no connec-

tions between the superficial and deep lymphatic systems

of the upper extremity throughout their courses when fully

functional and open; only when the flow of lymph has been

pathologically altered may connections between the two

systems be found.20 Physiologically functional connections

may be found in the axilla, along with junctions between

lymph nodes draining the upper extremity and nodes

draining the breast.11

Considering the lack of publications providing greater

detail on the lymphatic drainage of the upper extremity and

its course in the axilla, we elected to prepare lymphatic

vessels detected after the previous administration of color

contrast (patent blue). The results were evaluated from two

aspects that are important for axillary surgical intervention

and its complications in breast cancer patients. We exam-

ined if the superficial lymphatic drainage of the upper

extremity is fully separable from the superficial lymphatic

drainage of the chest and breast. We further endeavored to

find an explanation as to why lymphedema occurs in the

upper extremity after sentinel node biopsy in breast

carcinoma.

MATERIALS AND METHODS

The study was performed on 21 female and 2 male

cadavers with a mean age of 63 years, within 12 h of death

from internal diseases and with a negative history of

malignancy. Study protocol was approved by the Ethical

Committee and met the guidelines of First Faculty of

Medicine, Charles University in Prague and General Uni-

versity Hospital. After local warming of the chest and arms

to a temperature of 37 �C, 6–8 ml of patent blue dye

(Patentblau V�) was gradually administered intradermally

and subcutaneously periareolarly, and in the superomedial

part of both arms. In five cases, Gerota Mass—Berlin blau

(ferrum ferrocyanide in oil) was utilized.21 To increase the

transport of contrast material we performed nonspecific

manual massage of the tissue in central direction. After

visualization and careful dissection of the lymphatic ves-

sels and nodes, a digital record of their routes and location

was made. Afterward, on the basis of these records, a

scheme of superficial upper extremity and breast lymph-

atics was constructed.

Lymphatic Drainage of Breast and Upper Extremity 3411

RESULTS

In total, 46 observations were performed (23 cadavers

bilaterally). After application of contrast to the breast,

afferent collectors were visualized together with sentinel

nodes (Fig. 1), from which the contrast was directed along

the chest wall to cranial axillary nodes. The lymphatics of

the upper limb filled with contrast significantly slower, and

in eight cases were only partially visualized; contrast did

not penetrate to the axilla. In other cases, after application

of contrast to the subcutaneous and subfascial tissue of the

upper limb, 2–4 main afferent collectors were shown

(Figs. 1, 2). They were divided into a cranial and a caudal

collectors, and to 1–2 medial collectors according to their

number. All imaged collectors traversed the distal arm in a

parallel manner. After entering the axilla, the cranial and

medial collectors ran nearly parallel, while the caudal

collector deviated caudally and was directed to the lower

part of the axilla (Fig. 3).

The most cranial collectors also traveled alongside the

axillary vein and were directed to the apex of the axilla,

and was likely a collector for the deep lymphatic system of

the upper extremity (Fig. 2). In only one case was an

axillary node detected along the course of this collector.

Medial collectors [in 11 cases (24 %), two were visu-

alized] entered the large node that was located lateral to the

thoracodorsal group (Fig. 4). This node functioned as the

sentinel node for a particular part of the upper extremity.

The collector from this node was further directed to several

nodes in the central part of the axilla. In two cases, under

very favorable imaging conditions, collectors were also

imaged that were directed from the central nodes to the

apex of the axilla.

Caudally imaged collectors diverged from the axillary

vein in a medial and slightly caudal direction, and entered

the lymph nodes located in the caudal part of the axilla

(Fig. 3).

The nodes that initially drain the medial and caudal

collectors were shown to be the sentinel lymph nodes for

the (relevant) part of the upper extremity.

In five cases (11 %), the caudal collector entered a node

located in the caudal part of the axilla (Fig. 3), which was

already colored blue by previous contrast application to the

breast. We assumed that this was a sentinel node of the

breast. In six cases (13 %), we found sentinel lymph nodes

of the breast and sentinel nodes of upper limb in close

proximity (up to 1.5 cm). Their afferent collectors were

directed to the central axilla, and in three cases, these nodes

FIG. 1 Detail of dissected structures in right axilla. AV axillary vein,

PM pectoralis major muscle, LN sentinel node of upper extremity, SNsentinel node of the breast

FIG. 2 Detail of the right axilla. Medial afferent collector with

sentinel node of the arm (LN), AV axillary vein, PM pectoralis major

muscle

FIG. 3 Detail of dissected structures in left axilla. AV axillary vein,

N second intercostobrachialis nerve, CC cranial afferent collector, SNsentinel node of the breast, LN sentinel node of upper extremity, KCcaudal afferent collector, TD thoracodorsalis nerve

3412 D. Pavlista, O. Eliska

were connected by blue colored collectors. On the basis of

records of these findings, a scheme was constructed (Fig. 5).

DISCUSSION

Although the course of the lymphatic vessels imaged in

the present study are highly variable and postmortem

conditions are functionally different from those in vivo, the

findings we obtained suggest that a substantial portion of

lymph from the subcutaneous tissue of the upper limb

passes through the central axilla. One very interesting

finding is that a certain portion of lymph is fed into the

caudal part of the axilla toward the sentinel nodes of the

breast (24 % of all cases), and in five cases, even entered

them directly. The concordance of sentinel node of the

upper extremity and sentinel nodes of the breast or their

intimate vicinity is the probable cause of lymphedema after

sentinel node biopsy in breast cancer, and is consistent with

the results of previously published clinical studies. Boneti

described the frequent finding of a blue-colored collector in

the vicinity of the sentinel lymph node at biopsy after the

application of patent blue in the arm.22 Connection

between lymphatics of the arm and breast after injection of

patent blue in the arm was recently described by Rubio in

breast cancer patients after neoadjuvant chemotherapy. The

blue arm node was positive in 13 % of the patients with a

metastatic involvement of the axilla. Important issue in this

intraoperative study is that the group of patients with

higher likelihood of extensive nodal involvement will not

benefit from preserving the blue arm nodes (ARM).23

Similar findings were described by Ponzone.24 They sug-

gested that extensive metastatic involvement may favor the

occurrence of connections or reverse flow between the

breast and arm lymphatic pathways, making actually

impossible their anatomic and surgical subdivision.

We noted several differences between lymphatic map-

ping of the upper extremity and the breast. Imaging the

lymphatics of the upper extremity is more time consuming.

While breast lymphatics reliably appear within 20 min, in

visualizing the upper extremity lymphatics we had to wait

90 min. This was to our advantage as the breast lymphatics

had already been visualized. On the other hand, it was not

possible to completely assess the further spread of contrast

from nodes already imaged to the axilla. Therefore, in the

last 10 cases we first applied contrast to the upper

extremity, and after performing ARM, applied contrast to

the breast. Another notable finding was that while the

breast is preferentially drained to one sentinel node of

relatively constant localization, the upper extremity has

FIG. 4 Left axilla. Lymphatic collectors passing from the breast and

arm toward to axilla. AV axillary vein, PM pectoralis major muscle,

LN sentinel node of upper extremity, SN sentinel node of the breast,

N intercostobrachialis nerve

FIG. 5 Final scheme of lymphatic drainage of the breast and the

upper extremity in axilla. Black arrows indicate direction of patent

blue flow

Lymphatic Drainage of Breast and Upper Extremity 3413

several sentinel nodes that depend on the number and

course of collectors.25 Each collector, apart from the deep

collector, has its own sentinel node of the upper extremity.

This finding is not in agreement with the findings of Be-

drosian, who described only one ARM (sentinel) node of

the upper extremity.26 We believe that the reason is both in

the extensive application of a large amount of contrast

(6–8 ml) applied to numerous spots in the arm and also

with a sufficient amount of time devoted to the application,

imaging and preparation of lymphatics, which is not pos-

sible during operative procedures as a result of the

necessary destruction of tissues and extensive preparation.

Our findings also explain the fact that not all patients will

develop lymphedema after dissection of the axilla. If any of

the cranial and medial collector is retained during the

procedure, then this assumes the function of interrupted

collectors and reduces the risk of lymphedema. We were

unable to view expected anastomoses or even connections

between the lymphatic drainage of the upper extremity and

the breast in the apex of the axilla for technical reasons.

Lymphatics of the upper extremity were more difficult

to visualize in overweight patients. In three patients with a

high body mass index (over 35), only lymphatics in the arm

were appreciated, not in the axilla.

The results show that a proportion of lymph from the

subcutaneous upper extremity flows through sentinel node

and continues to the nodes in the central part of the axilla.

In some cases the lymph even continues to nodes in the

caudal part of the axilla, including the sentinel node of the

breast. Contrast therefore does not only flow centrally

toward the above nodes, but on the contrary, collectors can

reach the other (neighboring) axillary nodes, including

sentinel nodes of the breast. These collectors also represent

the main problem of the ARM concept because they may

pose potencional route for metastatic cancer cells in

sentinel node–positive breast cancer patients.

The interruption of lymphatic vessels (connectors) that

connect individual axillary lymph nodes can cause lymph-

edema of the upper extremity described after sentinel lymph

node biopsy, as has been repeatedly observed.5, 27 It can be

assumed that any surgical intervention in the axilla may

potentially result in the emergence of lymphedema of the

upper extremity, the severity of which is dependent upon the

variability and location of damage to the lymphatics. Addi-

tionally, interruption of these anastomoses may also explain

lymphorrheas and formation of surgery related lymphoceles,

problems which may appear independently of the arm

lymphedema.

Although the lymphatic drainage of the upper extremity

shows certain patterns, it is unpredictable as a result of its

great variability. Further studies, especially in vivo, are

need to obtain a deeper understanding of lymphatic

drainage of the breast and upper limb.

ACKNOWLEDGMENT Supported by Grant NS 9773-4 of the

Internal Grant Agency of the Ministry of Health of the Czech

Republic.

REFERENCES

1. Swenson KK, Nissen MJ, Ceronsky C, Swenson L, Lee MW,

Tuttle TM. Comparison of side effects between sentinel lymph

node and axillary lymph node dissection for breast cancer. AnnSurg Oncol. 2002;9:745–53.

2. Gerber L, Lampert M, Wood C, et al. Comparison of pain,

motion, and edema after modified radical mastectomy vs. local

excision with axillary dissection and radiation. Breast Cancer ResTreat. 1992;21:139–45.

3. Noguchi M. Axillary reverse mapping for breast cancer. BreastCancer Res Treat. 2010;119:529–35.

4. Thompson M, Korourian S, Henry-Tillman R, et al. Axillary

reverse mapping (ARM): a new concept to identify and enhance

lymphatic preservation. Ann Surg Oncol. 2007;14:1890–5.

5. Wilke LG, McCall LM, Posther KE, et al. Surgical complications

associated with sentinel lymph node biopsy: results from a pro-

spective international cooperative group trial. Ann Surg Oncol.2006;13:491–500.

6. Casabona F, Bogliolo S, Valenzano Menada M, Sala P, Villa G,

Ferrero S. Feasibility of axillary reverse mapping during sentinel

lymph node biopsy in breast cancer patients. Ann Surg Oncol.2009;16:2459–63.

7. Klimberg VS. A new concept toward the prevention of lymphe-

dema: axillary reverse mapping. J Surg Oncol. 2008;97:563–4.

8. Pressman PI. Surgical treatment and lymphedema. Cancer.

1998;83(12 Suppl Am):2782–7.

9. Ponzone R, Mininanni P, Cassina E, Sismondi P. Axillary reverse

mapping in breast cancer: can we spare what we find? Ann SurgOncol. 2008;15:390–1.

10. Suami H, Pan WR, Mann GB, Taylor GI. The lymphatic anatomy

of the breast and its implications for sentinel lymph node biopsy:

a human cadaver study. Ann Surg Oncol. 2008;15:863–71.

11. Suami H, Taylor GI, Pan WR. The lymphatic territories of the

upper limb: anatomical study and clinical implications. PlastReconstr Surg. 2007;119:1813–22.

12. Cruikshank C. The anatomy of the absorbing vessels of the

human body. London: G. Nicol, 1786.

13. Sappey C. Anatomie, physiologie, pathologie des vaisseaux

lymphatiques consideres chez l’homme at les vertebres. Paris: A.

Delahaye and E. Lecrosnier, 1874.

14. Delamere G, Poirier P, Cuneo B. The lymphatics. In: Charpy PP,

ed. A trearise of human anatomy. Westminster: Archibald Con-

stable, 1903.

15. Borgstein PJ, Meijer S, Pijpers RJ, van Diest PJ. Functional

lymphatic anatomy for sentinel node biopsy in breast cancer:

echoes from the past and the periareolar blue method. Ann Surg.2000;232:81–9.

16. Kett K, Szilagyi K, Anga B, Kett AG, Kiralyfalvi K. Axillary

lymph drainage as a prognostic factor of survival in breast cancer.

Lymphology. 2002;35:161–70.

17. Kelley MC, Hansen N, McMasters KM. Lymphatic mapping and

sentinel lymphadenectomy for breast cancer. Am J Surg.2004;188:49–61.

18. McMasters KM, Tuttle TM, Carlson DJ, et al. Sentinel lymph

node biopsy for breast cancer: a suitable alternative to routine

axillary dissection in multi-institutional practice when optimal

technique is used. J Clin Oncol. 2000;18:2560–6.

19. Pecha V, Kolarik D, Kozevnikova R, et al. Sentinel lymph node

biopsy in breast cancer patients treated with neoadjuvant che-

motherapy. Cancer. doi:10.1002/cncr.26102.

3414 D. Pavlista, O. Eliska

20. Suami H, Pan WR, Taylor GI. Changes in the lymph structure of

the upper limb after axillary dissection: radiographic and ana-

tomical study in a human cadaver. Plast Reconstr Surg. 2007;

120:982–91.

21. Gerota D. Zur Technik der Lymphgefassinjektion—Eine neue

Injektionsmasse fuer Lymphgefasse—Polychrome Injektion.

Anat Anz. 1896;12:216–24.

22. Boneti C, Korourian S, Diaz Z, et al. Scientific Impact Award.

Axillary reverse mapping (ARM) to identify and protect

lymphatics draining the arm during axillary lymphadenectomy.

Am J Surg. 2009;198:482–7.

23. Rubio I, Cebrecos I, Peg V, et al. Extensive nodal involvement

increases the positivity of blue nodes in the axillary reverse

mapping procedure in patients with breast cancer. J Surg Oncol.doi:10.1002/jso.23048.

24. Ponzone R, Cont N, Maggiorotto F, et al. Extensive nodal disease

may impair axillary reverse mapping in patients with breast

cancer. J Clin Oncol. 2009;33:5547–51.

25. Clough KB, Nasr R, Nos C, Vieira M, Inguenault C, Poulet B.

New anatomical classification of the axilla with implications for

sentinel node biopsy. Br J Surg. 2010;97:1659–65.

26. Bedrosian I, Babiera GV, Mittendorf EA, et al. A phase I study to

assess the feasibility and oncologic safety of axillary reverse

mapping in breast cancer patients. Cancer. 2010;116:2543–8.

27. Schrenk P, Rieger R, Shamiyeh A, Wayand W. Morbidity fol-

lowing sentinel lymph node biopsy versus axillary lymph node

dissection for patients with breast carcinoma. Cancer. 2000;88:

608–14.

Lymphatic Drainage of Breast and Upper Extremity 3415